Abetalipoproteinemia

Mendelian MONDO:0008692 Pathograph 56 Show in embeddings browser Hypobetalipoproteinemia

Abetalipoproteinemia is a severe autosomal recessive disorder of apoB-containing lipoprotein assembly and secretion caused by biallelic MTTP pathogenic variants. Loss of microsomal triglyceride transfer protein function prevents normal chylomicron export from enterocytes and VLDL export from hepatocytes, producing absent or extremely low apoB-containing lipoproteins, hypocholesterolemia, hypotriglyceridemia, fat malabsorption, and secondary fat-soluble vitamin deficiency. Infants typically present with failure to thrive, diarrhea, vomiting, steatorrhea, acanthocytosis, and abnormal lipid studies; untreated individuals can later develop retinal, neurologic, hematologic, hepatic, and coagulation complications. Management centers on a low-fat diet, essential fatty acid intake, and high-dose fat-soluble vitamin supplementation.

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1
Mappings
1
Inheritance
10
Pathophys.
40
Phenotypes
1
Hypotheses
56
Pathograph
1
Genes
1
Variants
5
Medical Actions
2
Differentials
15
References
1
Deep Research
1
Hyp. Reports
🏷

Classifications

Harrison's Part
GENETICS ENVIRONMENT DISEASE
🔗

Mappings

MONDO
MONDO:0008692 abetalipoproteinemia
skos:exactMatch Orphanet ORPHA:14
The structured Orphanet record lists MONDO:0008692 as an exact cross-reference for abetalipoproteinemia.
👪

Inheritance

1
Autosomal Recessive HP:0000007
Autosomal recessive inheritance
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"Autosomal recessive"
Orphanet classifies Abetalipoproteinemia inheritance as autosomal recessive.
PMID:30358967 SUPPORT Other
"inherited in an autosomal recessive"
GeneReviews states that abetalipoproteinemia is inherited in an autosomal recessive manner.
◈

Mechanistic Hypotheses

1
Canonical MTTP ApoB-Lipoprotein Assembly Model
canonical_mttp_lipoprotein_assembly_model CANONICAL
Evidence balance 3 support
Biallelic MTTP loss of function disrupts the microsomal triglyceride transfer protein complex and prevents normal assembly and secretion of intestinal apoB48-containing chylomicrons and hepatic apoB100-containing VLDL. The resulting absence of apoB lipoproteins produces severe hypolipidemia, intestinal fat and fat-soluble-vitamin malabsorption, hepatic triglyceride retention, and downstream multisystem complications.
The proximal MTTP-to-apoB-assembly mechanism is established. The detailed intermediates linking apoB-lipoprotein absence to acanthocyte formation remain incompletely resolved, and this entry does not treat retinal MTTP expression or single hypomorphic cases as established alternative disease mechanisms or genotype-phenotype rules.
Pathograph links
MTTP Loss of Function -> Defective ApoB Lipidation and Particle Assembly DIRECT Loss of MTP lipid-transfer activity prevents normal lipidation and assembly of nascent apoB-containing particles.
Defective ApoB Lipidation and Particle Assembly -> Failed Chylomicron and VLDL Secretion DIRECT Particles that cannot be assembled and lipidated are not normally secreted from enterocytes or hepatocytes.
Failed Chylomicron and VLDL Secretion -> Impaired Intestinal Lipid Absorption INDIRECT KNOWN INTERMEDIATES Absent intestinal chylomicron export disrupts absorption and transport of dietary lipid. Intermediates: absent apoB48-containing chylomicron export from enterocytes
Failed Chylomicron and VLDL Secretion -> Acanthocytosis and Hemolysis INDIRECT UNKNOWN INTERMEDIATES ApoB-lipoprotein absence is accompanied by acanthocytosis and hemolytic findings, but the detailed membrane-lipid intermediates remain incompletely resolved.
Failed Chylomicron and VLDL Secretion -> Hepatic Triglyceride Retention INDIRECT KNOWN INTERMEDIATES Impaired hepatic VLDL export retains triglyceride in hepatocytes. Intermediates: failure to export triglyceride in apoB100-containing VLDL
Impaired Intestinal Lipid Absorption -> Reduced Fat-Soluble Vitamin Bioavailability INDIRECT KNOWN INTERMEDIATES Chylomicron failure impairs absorption and transport of vitamins A, D, E, and K. Intermediates: impaired intestinal uptake and transport of fat-soluble vitamins
Reduced Fat-Soluble Vitamin Bioavailability -> Vitamin A/E-Associated Retinal Degeneration INDIRECT KNOWN INTERMEDIATES Chronic vitamin A and E deficiency contributes to progressive retinal degeneration. Intermediates: inadequate vitamin delivery to retinal tissues
Reduced Fat-Soluble Vitamin Bioavailability -> Vitamin E-Associated Neuromuscular Injury INDIRECT KNOWN INTERMEDIATES Chronic vitamin E deficiency contributes to progressive neuropathy and myopathy. Intermediates: inadequate vitamin E delivery to neural and muscle tissues
Reduced Fat-Soluble Vitamin Bioavailability -> Vitamin K-Related Coagulopathy INDIRECT KNOWN INTERMEDIATES Reduced vitamin K bioavailability impairs normal coagulation. Intermediates: reduced vitamin-K-dependent coagulation activity
Deep research
OpenScientist citations 32 citations 2026-05-23T01:43:14.704225
Show evidence (3 references)
PMID:1439810 SUPPORT Human Clinical
"MTP activity and the 88-kilodalton component of MTP were present in intestinal biopsy samples from eight control individuals but were absent in four abetalipoproteinemic subjects."
Human intestinal-biopsy data directly demonstrate absent MTP protein and activity in affected individuals.
PMID:7782284 SUPPORT In Vitro
"only the normal subunit was able to form a stable, soluble complex with protein disulfide-isomerase"
Functional reconstitution shows that a disease-associated truncation disrupts the MTP-PDI complex.
PMID:33994405 SUPPORT Other
"Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver"
The contemporary review states the canonical proximal mechanism in the affected intestinal and hepatic compartments.
⚙

Pathophysiology

10
MTTP Loss of Function
Biallelic pathogenic MTTP variants reduce or abolish microsomal triglyceride transfer protein activity. MTP normally forms a lipid-transfer complex with protein disulfide isomerase; loss of the functional complex prevents normal lipidation of nascent apoB.
Canonical MTTP ApoB-Lipoprotein Assembly Model
MTTP hgnc:7467 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves MTTP (hgnc:7467). hgnc:7467 is a gene from the HUGO Gene Nomenclature Committee.
triglyceride transport GO:0034197 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased triglyceride transport (GO:0034197). GO:0034197 is a biological process from the Gene Ontology. ↓ DECREASED lipoprotein metabolic process GO:0042157 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased lipoprotein metabolic process (GO:0042157). GO:0042157 is a biological process from the Gene Ontology. ↓ DECREASED
lipid transfer activity GO:0120013 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves decreased lipid transfer activity (GO:0120013). GO:0120013 is a molecular function from the Gene Ontology. ↓ DECREASED apolipoprotein binding GO:0034185 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves decreased apolipoprotein binding (GO:0034185). GO:0034185 is a molecular function from the Gene Ontology. ↓ DECREASED
Downstream
Defective ApoB Lipidation and Particle Assembly Loss of MTP lipid-transfer activity prevents normal lipidation and assembly of nascent apoB-containing particles. Canonical MTTP ApoB-Lipoprotein Assembly Model
Show evidence (3 references)
ORPHA:14 SUPPORT Other
"MTTP | microsomal triglyceride transfer protein | hgnc:7467 | Disease-causing germline mutation(s) in"
Orphanet records MTTP as the disease-causing gene.
PMID:1439810 SUPPORT Human Clinical
"MTP activity and the 88-kilodalton component of MTP were present in intestinal biopsy samples from eight control individuals but were absent in four abetalipoproteinemic subjects."
Human intestinal biopsies directly demonstrate absent MTP protein and activity.
PMID:7782284 SUPPORT In Vitro
"only the normal subunit was able to form a stable, soluble complex with protein disulfide-isomerase"
Functional reconstitution shows disruption of the required MTP-PDI complex by a patient-derived truncation.
Defective ApoB Lipidation and Particle Assembly
MTP deficiency prevents the lipidation and assembly of apoB48-containing chylomicrons in enterocytes and apoB100-containing VLDL particles in hepatocytes.
Canonical MTTP ApoB-Lipoprotein Assembly Model
enterocyte CL:0000584 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves enterocyte (CL:0000584). CL:0000584 is a cell type from the Cell Ontology. hepatocyte CL:0000182 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves hepatocyte (CL:0000182). CL:0000182 is a cell type from the Cell Ontology.
chylomicron assembly GO:0034378 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased chylomicron assembly (GO:0034378). GO:0034378 is a biological process from the Gene Ontology. ↓ DECREASED very-low-density lipoprotein particle assembly GO:0034379 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased very-low-density lipoprotein particle assembly (GO:0034379). GO:0034379 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Failed Chylomicron and VLDL Secretion Particles that cannot be assembled and lipidated are not normally secreted from enterocytes or hepatocytes. Canonical MTTP ApoB-Lipoprotein Assembly Model
Show evidence (1 reference)
PMID:33994405 SUPPORT Other
"Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver"
The review supports failed apoB-particle assembly in both affected tissues.
Failed Chylomicron and VLDL Secretion
Failed secretion of intestinal chylomicrons and hepatic VLDL leaves apoB-containing lipoproteins virtually absent from plasma, impairs dietary lipid transport, and prevents normal export of hepatic triglyceride.
Canonical MTTP ApoB-Lipoprotein Assembly Model
enterocyte CL:0000584 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves enterocyte (CL:0000584). CL:0000584 is a cell type from the Cell Ontology. hepatocyte CL:0000182 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves hepatocyte (CL:0000182). CL:0000182 is a cell type from the Cell Ontology.
lipid transport GO:0006869 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased lipid transport (GO:0006869). GO:0006869 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Impaired Intestinal Lipid Absorption Absent intestinal chylomicron export disrupts absorption and transport of dietary lipid. Canonical MTTP ApoB-Lipoprotein Assembly Model
Absent apoB-containing lipoproteins Failed chylomicron and VLDL secretion is measured as absent or extremely low circulating apoB-containing lipoproteins.
Abnormal circulating apolipoprotein concentration Circulating apoB is absent or extremely low.
Hypocholesterolemia Loss of apoB-containing particles produces severe hypocholesterolemia.
Decreased LDL cholesterol concentration LDL cholesterol is absent or extremely low because its apoB-containing precursors are not secreted normally.
Decreased HDL cholesterol concentration HDL cholesterol can also be decreased, although the intervening mechanism is not resolved here.
Hypotriglyceridemia Loss of chylomicron and VLDL secretion produces extremely low circulating triglyceride.
Acanthocytosis and Hemolysis ApoB-lipoprotein absence is accompanied by acanthocytosis and hemolytic findings, but the detailed membrane-lipid intermediates remain incompletely resolved. Canonical MTTP ApoB-Lipoprotein Assembly Model
Hepatic Triglyceride Retention Impaired hepatic VLDL export retains triglyceride in hepatocytes. Canonical MTTP ApoB-Lipoprotein Assembly Model
Show evidence (1 reference)
PMID:24288038 SUPPORT Other
"virtually absent apo B-containing lipoproteins, including chylomicrons, very low density lipoprotein and low density lipoprotein."
The review supports the characteristic absence of chylomicrons, VLDL, and LDL.
Impaired Intestinal Lipid Absorption
Failure to export chylomicrons from enterocytes impairs absorption and transport of dietary fat, causing steatorrhea, gastrointestinal symptoms, inadequate caloric utilization, and early growth failure.
Canonical MTTP ApoB-Lipoprotein Assembly Model
enterocyte CL:0000584 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves enterocyte (CL:0000584). CL:0000584 is a cell type from the Cell Ontology.
intestinal lipid absorption GO:0098856 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased intestinal lipid absorption (GO:0098856). GO:0098856 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Fat malabsorption Defective chylomicron export produces impaired dietary fat absorption.
Steatorrhea Unabsorbed dietary fat produces steatorrhea.
Chronic diarrhea Intestinal fat malabsorption contributes to chronic diarrhea.
Vomiting Vomiting is part of the characteristic infantile gastrointestinal presentation.
Failure to thrive Reduced absorption of dietary calories contributes to early growth failure.
Reduced Fat-Soluble Vitamin Bioavailability Chylomicron failure impairs absorption and transport of vitamins A, D, E, and K. Canonical MTTP ApoB-Lipoprotein Assembly Model
Show evidence (1 reference)
PMID:33994405 SUPPORT Other
"Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy."
The review identifies the characteristic clinical consequences of the intestinal branch.
Reduced Fat-Soluble Vitamin Bioavailability
Impaired absorption and lipoprotein transport reduce the bioavailability of vitamins A, D, E, and K. Tissue deficiency drives retinal, neurologic, skeletal, and coagulation complications.
Canonical MTTP ApoB-Lipoprotein Assembly Model
Downstream
Reduced circulating vitamin A concentration Reduced vitamin A absorption and transport lowers circulating vitamin A.
Decreased circulating vitamin D concentration Reduced vitamin D absorption and transport lowers circulating vitamin D.
Decreased circulating vitamin E concentration Reduced vitamin E absorption and transport lowers circulating vitamin E.
Low fat-soluble vitamin concentrations The combined vitamin-deficiency state is measurable in blood.
Osteopenia Reduced vitamin D bioavailability can contribute to reduced bone density.
Vitamin A/E-Associated Retinal Degeneration Chronic vitamin A and E deficiency contributes to progressive retinal degeneration. Canonical MTTP ApoB-Lipoprotein Assembly Model
Vitamin E-Associated Neuromuscular Injury Chronic vitamin E deficiency contributes to progressive neuropathy and myopathy. Canonical MTTP ApoB-Lipoprotein Assembly Model
Vitamin K-Related Coagulopathy Reduced vitamin K bioavailability impairs normal coagulation. Canonical MTTP ApoB-Lipoprotein Assembly Model
Show evidence (1 reference)
PMID:33994405 SUPPORT Other
"Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia."
The review supports reduced fat-soluble-vitamin bioavailability downstream of the MTTP defect.
Vitamin A/E-Associated Retinal Degeneration
Chronic vitamin A and E deficiency is associated with progressive retinal degeneration, abnormal retinal pigmentation, night and color vision loss, and eventual severe visual impairment. The entry does not assume a separate tissue-autonomous MTTP mechanism.
Downstream
Progressive visual loss Progressive retinal dysfunction causes worsening visual loss.
Rod-cone dystrophy Retinal degeneration can present with a rod-cone dystrophy pattern.
Color vision defect Progressive retinal dysfunction can impair color vision.
Nyctalopia Rod-predominant retinal dysfunction causes night blindness.
Abnormal retinal pigmentation Untreated retinal degeneration can produce abnormal retinal pigmentation.
Show evidence (2 references)
PMID:26086616 SUPPORT Other
"later in life, with progressive ophthalmopathy and neuropathy as a result of deficiency of the fat-soluble vitamins A and E."
The review supports the vitamin-deficiency retinal branch.
PMID:30358967 SUPPORT Other
"Untreated individuals may develop atypical pigmentation of the retina"
GeneReviews describes untreated retinal pigmentation and progressive visual dysfunction.
Vitamin E-Associated Neuromuscular Injury
Chronic vitamin E deficiency is associated with progressive peripheral neuropathy, posterior-column sensory dysfunction, loss of reflexes, weakness, myopathy, dysarthria, and ataxia.
Downstream
Areflexia Progressive neurologic disease can cause loss of deep tendon reflexes.
Ataxia Sensory and neuromuscular dysfunction can produce ataxia.
Dysarthria Progressive neuromuscular involvement can cause dysarthria.
Impaired vibratory sensation Posterior-column and sensory-nerve dysfunction impairs vibration sense.
Impaired proprioception Posterior-column and sensory-nerve dysfunction impairs proprioception.
Peripheral neuropathy Vitamin-deficiency-associated injury can produce progressive peripheral neuropathy.
Myopathy Neuromuscular involvement can include myopathy.
Muscle weakness Neuropathy and myopathy can cause progressive muscle weakness.
Pes cavus Chronic peripheral neuromuscular disease can be accompanied by pes cavus.
Show evidence (2 references)
PMID:26086616 SUPPORT Other
"later in life, with progressive ophthalmopathy and neuropathy as a result of deficiency of the fat-soluble vitamins A and E."
The review supports vitamin-deficiency-associated neuropathy.
PMID:30358967 SUPPORT Other
"deep tendon reflexes, vibratory sense, and proprioception; muscle weakness; dysarthria; and ataxia typically manifest"
GeneReviews describes the characteristic neuromuscular manifestations.
Acanthocytosis and Hemolysis
Abetalipoproteinemia is accompanied by acanthocytic erythrocyte morphology and can include anemia, reticulocytosis, hemolysis, and secondary hyperbilirubinemia. The detailed membrane-lipid pathway from apoB-particle absence to acanthocyte formation remains incompletely resolved.
erythrocyte CL:0000232 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves erythrocyte (CL:0000232). CL:0000232 is a cell type from the Cell Ontology.
Downstream
Acanthocytosis Altered erythrocyte morphology is observed as acanthocytosis.
Anemia Hemolysis can contribute to anemia.
Reticulocytosis Compensatory erythropoiesis can produce reticulocytosis.
Hyperbilirubinemia Erythrocyte destruction increases bilirubin production.
Show evidence (1 reference)
PMID:30358967 SUPPORT Other
"Hematologic manifestations may include acanthocytosis (irregularly spiculated erythrocytes), anemia, reticulocytosis, and hemolysis with resultant hyperbilirubinemia."
GeneReviews directly supports the linked hematologic manifestation set.
Hepatic Triglyceride Retention
Failure to export triglyceride in apoB100-containing VLDL promotes lipid retention in hepatocytes. Steatosis is variably expressed and can rarely progress to fibrosis or cirrhosis.
hepatocyte CL:0000182 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves hepatocyte (CL:0000182). CL:0000182 is a cell type from the Cell Ontology.
lipid storage GO:0019915 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased lipid storage (GO:0019915). GO:0019915 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Hepatomegaly Hepatic lipid accumulation can enlarge the liver.
Hepatic steatosis Hepatocyte triglyceride retention is observed as hepatic steatosis.
Hepatic fibrosis Chronic hepatic injury can progress to fibrosis.
Cirrhosis Advanced chronic hepatic injury can rarely progress to cirrhosis.
Hypoalbuminemia Hepatic or nutritional involvement can be accompanied by hypoalbuminemia.
Show evidence (2 references)
PMID:32039990 SUPPORT Other
"Fatty liver, cirrhosis and hepatocellular carcinoma have been reported in FHBL and ABL probably due to decreased triglyceride export from the liver."
The review supports hepatic triglyceride-export failure as the likely mechanism of liver disease.
PMID:24842304 SUPPORT Human Clinical
"They suggest that the genetic defect in VLDL assembly is critical for the occurrence of liver steatosis leading to fibrosis"
A human ABL/FHBL cohort supports the VLDL-assembly defect as critical to steatosis and fibrosis.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Abetalipoproteinemia Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

40
Blood 3
Anemia FREQUENT HP:0001903 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anemia (HP:0001903). HP:0001903 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0001903 | Anemia | Frequent (79-30%)"
Orphanet records anemia as frequent.
Reticulocytosis FREQUENT HP:0001923 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Reticulocytosis (HP:0001923). HP:0001923 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0001923 | Reticulocytosis | Frequent (79-30%)"
Orphanet records reticulocytosis as frequent.
Abnormal bleeding VERY_RARE HP:0001892 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abnormal bleeding (HP:0001892). HP:0001892 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0001892 | Abnormal bleeding | Very rare (<4-1%)"
Orphanet records abnormal bleeding as a very rare phenotype.
Digestive 7
Steatorrhea VERY_FREQUENT HP:0002570 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Steatorrhea (HP:0002570). HP:0002570 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0002570 | Steatorrhea | Very frequent (99-80%)"
Orphanet records steatorrhea as very frequent.
Chronic diarrhea FREQUENT HP:0002028 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Chronic diarrhea (HP:0002028). HP:0002028 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0002028 | Chronic diarrhea | Frequent (79-30%)"
Orphanet records chronic diarrhea as frequent.
PMID:30358967 SUPPORT Other
"with failure to thrive, diarrhea, vomiting, and malabsorption of fat."
GeneReviews supports diarrhea as part of the typical infant presentation.
Vomiting OCCASIONAL HP:0002013 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vomiting (HP:0002013). HP:0002013 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0002013 | Vomiting | Occasional (29-5%)"
Orphanet records vomiting as an occasional phenotype.
PMID:33994405 SUPPORT Other
"Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy."
The review identifies vomiting as part of the typical infantile presentation.
Hepatomegaly OCCASIONAL HP:0002240 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hepatomegaly (HP:0002240). HP:0002240 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0002240 | Hepatomegaly | Occasional (29-5%)"
Orphanet records hepatomegaly as occasional.
Hepatic steatosis OCCASIONAL HP:0001397 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hepatic steatosis (HP:0001397). HP:0001397 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0001397 | Hepatic steatosis | Occasional (29-5%)"
Orphanet records hepatic steatosis as occasional.
Hepatic fibrosis VERY_RARE HP:0001395 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hepatic fibrosis (HP:0001395). HP:0001395 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0001395 | Hepatic fibrosis | Very rare (<4-1%)"
Orphanet records hepatic fibrosis as a very rare phenotype.
Cirrhosis VERY_RARE HP:0001394 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cirrhosis (HP:0001394). HP:0001394 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0001394 | Cirrhosis | Very rare (<4-1%)"
Orphanet records cirrhosis as a very rare phenotype.
PMID:32039990 SUPPORT Other
"Fatty liver, cirrhosis and hepatocellular carcinoma have been reported in FHBL and ABL"
The liver review reports cirrhosis among documented ABL liver outcomes.
Eye 5
Progressive visual loss FREQUENT HP:0000529 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Progressive visual loss (HP:0000529). HP:0000529 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0000529 | Progressive visual loss | Frequent (79-30%)"
Orphanet records progressive visual loss as frequent.
Rod-cone dystrophy OCCASIONAL HP:0000510 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Rod-cone dystrophy (HP:0000510). HP:0000510 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0000510 | Rod-cone dystrophy | Occasional (29-5%)"
Orphanet records rod-cone dystrophy as an occasional phenotype.
Color vision defect FREQUENT HP:0000551 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Color vision defect (HP:0000551). HP:0000551 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0000551 | Color vision defect | Frequent (79-30%)"
Orphanet records color vision defect as frequent.
PMID:30358967 SUPPORT Other
"with progressive loss of night vision and/or color vision in adulthood."
GeneReviews supports acquired loss of color vision as a retinal manifestation.
Nyctalopia FREQUENT HP:0000662 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Nyctalopia (HP:0000662). HP:0000662 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0000662 | Nyctalopia | Frequent (79-30%)"
Orphanet records nyctalopia as frequent.
PMID:30358967 SUPPORT Other
"with progressive loss of night vision and/or color vision in adulthood."
GeneReviews supports night vision loss as a retinal manifestation.
Abnormal retinal pigmentation FREQUENT HP:0007703 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abnormal retinal pigmentation (HP:0007703). HP:0007703 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0007703 | Abnormality of retinal pigmentation | Frequent (79-30%)"
Orphanet records abnormal retinal pigmentation as frequent.
Limbs 1
Pes cavus OCCASIONAL HP:0001761 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pes cavus (HP:0001761). HP:0001761 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0001761 | Pes cavus | Occasional (29-5%)"
Orphanet records pes cavus as an occasional phenotype.
Metabolism 3
Decreased HDL cholesterol concentration FREQUENT HP:0003233 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Decreased HDL cholesterol concentration (HP:0003233). HP:0003233 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0003233 | Decreased HDL cholesterol concentration | Frequent (79-30%)"
Orphanet records decreased HDL cholesterol concentration as frequent.
Hypoalbuminemia FREQUENT HP:0003073 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypoalbuminemia (HP:0003073). HP:0003073 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0003073 | Hypoalbuminemia | Frequent (79-30%)"
Orphanet records hypoalbuminemia as frequent.
Elevated circulating hepatic transaminase concentration OCCASIONAL HP:0002910 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Elevated circulating hepatic transaminase concentration (HP:0002910). HP:0002910 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0002910 | Elevated circulating hepatic transaminase concentration | Occasional (29-5%)"
Orphanet records elevated circulating hepatic transaminases as an occasional phenotype.
Musculoskeletal 3
Osteopenia OCCASIONAL HP:0000938 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Osteopenia (HP:0000938). HP:0000938 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0000938 | Osteopenia | Occasional (29-5%)"
Orphanet records osteopenia as an occasional phenotype.
Myopathy OCCASIONAL HP:0003198 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Myopathy (HP:0003198). HP:0003198 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0003198 | Myopathy | Occasional (29-5%)"
Orphanet records myopathy as an occasional phenotype.
PMID:33994405 SUPPORT Other
"neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.)"
The contemporary review lists myopathy among later neuromuscular manifestations.
Muscle weakness HP:0001324 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Muscle weakness (HP:0001324). HP:0001324 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:30358967 SUPPORT Other
"deep tendon reflexes, vibratory sense, and proprioception; muscle weakness;"
GeneReviews includes muscle weakness among untreated neuromuscular findings.
Nervous System 4
Areflexia FREQUENT HP:0001284 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Areflexia (HP:0001284). HP:0001284 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0001284 | Areflexia | Frequent (79-30%)"
Orphanet records areflexia as frequent.
PMID:30358967 SUPPORT Other
"deep tendon reflexes, vibratory sense, and proprioception; muscle weakness;"
GeneReviews describes progressive loss of deep tendon reflexes in untreated individuals.
Ataxia OCCASIONAL HP:0001251 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ataxia (HP:0001251). HP:0001251 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0001251 | Ataxia | Occasional (29-5%)"
Orphanet records ataxia as an occasional phenotype.
PMID:30358967 SUPPORT Other
"dysarthria; and ataxia typically manifest"
GeneReviews describes ataxia among neuromuscular findings in untreated individuals.
Dysarthria OCCASIONAL HP:0001260 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dysarthria (HP:0001260). HP:0001260 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0001260 | Dysarthria | Occasional (29-5%)"
Orphanet records dysarthria as an occasional phenotype.
PMID:30358967 SUPPORT Other
"dysarthria; and ataxia typically manifest"
GeneReviews describes dysarthria among neuromuscular findings in untreated individuals.
Peripheral neuropathy HP:0009830 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Peripheral neuropathy (HP:0009830). HP:0009830 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:33994405 SUPPORT Other
"neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.)"
The contemporary review lists peripheral neuropathy among later neuromuscular manifestations.
Growth 1
Failure to thrive FREQUENT HP:0001508 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Failure to thrive (HP:0001508). HP:0001508 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0001508 | Failure to thrive | Frequent (79-30%)"
Orphanet records failure to thrive as frequent.
Other 13
Abnormal circulating apolipoprotein concentration VERY_FREQUENT HP:0025201 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abnormal circulating apolipoprotein concentration (HP:0025201). HP:0025201 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0025201 | Abnormal circulating apolipoprotein concentration | Very frequent (99-80%)"
Orphanet records abnormal circulating apolipoprotein concentration as very frequent.
Hypocholesterolemia FREQUENT HP:0003146 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypocholesterolemia (HP:0003146). HP:0003146 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0003146 | Hypocholesterolemia | Frequent (79-30%)"
Orphanet records hypocholesterolemia as frequent.
PMID:24288038 SUPPORT Other
"are rare diseases characterized by hypocholesterolemia and"
This review describes hypocholesterolemia as a core feature.
Decreased LDL cholesterol concentration FREQUENT HP:0003563 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Decreased LDL cholesterol concentration (HP:0003563). HP:0003563 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0003563 | Decreased LDL cholesterol concentration | Frequent (79-30%)"
Orphanet records decreased LDL cholesterol concentration as frequent.
PMID:30358967 SUPPORT Other
"proband with absent or extremely low LDL-cholesterol, triglyceride, and"
GeneReviews describes absent or extremely low LDL cholesterol as a diagnostic biochemical feature.
Hypotriglyceridemia FREQUENT HP:0012153 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypotriglyceridemia (HP:0012153). HP:0012153 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0012153 | Hypotriglyceridemia | Frequent (79-30%)"
Orphanet records hypotriglyceridemia as frequent.
Fat malabsorption VERY_FREQUENT HP:0002630 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fat malabsorption (HP:0002630). HP:0002630 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0002630 | Fat malabsorption | Very frequent (99-80%)"
Orphanet records fat malabsorption as very frequent.
Reduced circulating vitamin A concentration FREQUENT HP:0004905 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Reduced circulating vitamin A concentration (HP:0004905). HP:0004905 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0004905 | Low levels of vitamin A | Frequent (79-30%)"
Orphanet records low vitamin A levels as frequent.
Decreased circulating vitamin D concentration FREQUENT HP:0100512 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Decreased circulating vitamin D concentration (HP:0100512). HP:0100512 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0100512 | Low levels of vitamin D | Frequent (79-30%)"
Orphanet records low vitamin D levels as frequent.
Decreased circulating vitamin E concentration VERY_FREQUENT HP:0100513 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Decreased circulating vitamin E concentration (HP:0100513). HP:0100513 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0100513 | Low levels of vitamin E | Very frequent (99-80%)"
Orphanet records low vitamin E levels as very frequent.
Acanthocytosis VERY_FREQUENT HP:0001927 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Acanthocytosis (HP:0001927). HP:0001927 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0001927 | Acanthocytosis | Very frequent (99-80%)"
Orphanet records acanthocytosis as very frequent.
PMID:30358967 SUPPORT Other
"Hematologic manifestations may include acanthocytosis (irregularly spiculated"
GeneReviews supports acanthocytosis as a hematologic manifestation.
Hyperbilirubinemia FREQUENT HP:0002904 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hyperbilirubinemia (HP:0002904). HP:0002904 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"HP:0002904 | Hyperbilirubinemia | Frequent (79-30%)"
Orphanet records hyperbilirubinemia as frequent.
Impaired vibratory sensation OCCASIONAL HP:0002495 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Impaired vibratory sensation (HP:0002495). HP:0002495 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0002495 | Impaired vibratory sensation | Occasional (29-5%)"
Orphanet records impaired vibratory sensation as an occasional phenotype.
PMID:30358967 SUPPORT Other
"deep tendon reflexes, vibratory sense, and proprioception; muscle weakness;"
GeneReviews describes progressive loss of vibratory sense in untreated individuals.
Impaired proprioception OCCASIONAL HP:0010831 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Impaired proprioception (HP:0010831). HP:0010831 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0010831 | Impaired proprioception | Occasional (29-5%)"
Orphanet records impaired proprioception as an occasional phenotype.
PMID:30358967 SUPPORT Other
"deep tendon reflexes, vibratory sense, and proprioception; muscle weakness;"
GeneReviews describes progressive loss of proprioception in untreated individuals.
Prolonged prothrombin time OCCASIONAL HP:0008151 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Prolonged prothrombin time (HP:0008151). HP:0008151 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"HP:0008151 | Prolonged prothrombin time | Occasional (29-5%)"
Orphanet records prolonged prothrombin time as occasional.
PMID:30358967 SUPPORT Other
"result in an increased international normalized ratio (INR)."
GeneReviews links fat-soluble vitamin malabsorption to increased INR.
🧬

Genetic Associations

1
MTTP pathogenic variants (Causative biallelic pathogenic variants)
Gene: MTTP hgnc:7467 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is MTTP (hgnc:7467). hgnc:7467 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE variant_origin: GERMLINE
Autosomal recessive inheritance
Show evidence (2 references)
ORPHA:14 SUPPORT Other
"MTTP | microsomal triglyceride transfer protein | hgnc:7467 | Disease-causing germline mutation(s) in"
Orphanet records MTTP as a disease-causing germline gene for Abetalipoproteinemia.
PMID:30358967 SUPPORT Other
"biallelic pathogenic variants in MTTP"
GeneReviews supports biallelic MTTP pathogenic variants as diagnostic for Abetalipoproteinemia.
Variants (1)
Biallelic MTTP pathogenic variants Pathogenic
Gene: MTTP hgnc:7467 HUGO Gene Nomenclature Committee (hgnc) Relation: this variant is in this gene This variant is in MTTP (hgnc:7467). hgnc:7467 is a gene from the HUGO Gene Nomenclature Committee. loss of function variant
Reported disease-causing MTTP variants include frameshift, splice-site, and missense variants; functional studies show that selected missense variants can impair MTP lipid-transfer activity or formation of the active MTP complex.
Functional effects
MTP lipid transfer activity loss-of-function
Pathogenic variants reduce functional MTP activity or disrupt active MTP complex formation.
Show evidence (3 references)
PMID:30358967 SUPPORT Other
"biallelic pathogenic variants in MTTP"
GeneReviews identifies biallelic MTTP pathogenic variants as the molecular diagnostic cause.
PMID:10946006 SUPPORT Human Clinical
"Three novel mutations have been identified: a frameshift mutation caused by a single adenine deletion at position 1389 of the cDNA, and a missense mutation, Asn780Tyr, each in homozygous forms; and a splice site mutation, 2218-2A-->G, in a compound heterozygous form."
Patient variant screening identified frameshift, missense, and splice-site MTTP mutations in ABL.
PMID:8939939 SUPPORT In Vitro
"Biochemical analysis of lysates from these cells showed that the Arg to His conversion interrupted the interaction between the 97-kDa subunit and protein disulfide isomerase."
Functional evidence shows one MTTP missense variant disrupts formation of the MTP complex.
💊

Medical Actions

5
Calorie-adequate low-fat diet
Category: Therapeutic Action: dietary interventionNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is dietary intervention (NCIT:C15447). NCIT:C15447 is a clinical intervention from the NCI Thesaurus. Ontology label: Dietary Intervention NCIT:C15447
Management guidance recommends adequate calories for growth together with a low-fat diet, generally limiting long-chain fat that cannot be transported normally in chylomicrons. This reduces gastrointestinal fat load but does not correct the MTTP defect.
Mechanism Target:
MODULATES Impaired Intestinal Lipid Absorption — Reducing dietary long-chain fat limits the substrate burden on the impaired intestinal transport pathway.
Show evidence (1 reference)
PMID:30358967 SUPPORT Other
"low-fat diet (10%-20% of total calories from fat)"
GeneReviews provides the low-fat dietary management framework.
Show evidence (2 references)
PMID:30358967 SUPPORT Other
"Adequate caloric intake to alleviate growth deficiency; low-fat diet (10%-20% of total calories from fat)"
GeneReviews recommends adequate calories and a low-fat diet for growth and gastrointestinal management.
PMID:30358967 SUPPORT Other
"Fatty foods, particularly those rich in long-chain fatty acids."
GeneReviews identifies long-chain-fat-rich foods as the principal dietary exposure to avoid.
High-dose fat-soluble vitamin supplementation
Category: Therapeutic Action: nutritional supplementationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is nutritional supplementation, annotated with Nutritional Support (NCIT:C15433). NCIT:C15433 is a clinical intervention from the NCI Thesaurus. Ontology label: Nutritional Support NCIT:C15433
Long-term vitamins A, D, E, and K replace nutrients that remain poorly absorbed. Observational evidence suggests early replacement may prevent or delay retinal and neuromuscular progression, but established dysfunction is not reliably reversed. Dosing requires specialist biochemical monitoring; vitamin A needs pregnancy-specific adjustment because excess can harm the developing fetus.
Mechanism Target:
MODULATES Reduced Fat-Soluble Vitamin Bioavailability — High-dose replacement increases vitamin availability despite persistent intestinal malabsorption without restoring normal chylomicron transport.
Show evidence (1 reference)
PMID:33994405 SUPPORT Other
"High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications"
The review supports replacement as the treatment mainstay while using appropriately qualified benefit language.
MODULATES Vitamin A/E-Associated Retinal Degeneration — Vitamin A and E replacement may slow retinal deterioration, particularly when started early.
Show evidence (1 reference)
PMID:7171526 SUPPORT Human Clinical
"After initiation of vitamin A and E therapy no progression of disturbed visual function could be detected in any patient."
An eight-patient follow-up observed stable retinal function after combined vitamin therapy.
MODULATES Vitamin E-Associated Neuromuscular Injury — High-dose vitamin E may slow or arrest progressive neuropathy and myopathy, but the evidence is observational.
Show evidence (1 reference)
PMID:2981135 SUPPORT Human Clinical
"It was concluded that treatment with high doses of vitamin E was responsible for the arrest of the usually progressive neuropathy and myopathy."
A long-term single-patient observation supports possible arrest of progressive neuromuscular disease.
Show evidence (2 references)
PMID:33994405 SUPPORT Other
"However, it cannot fully prevent or restore impaired function."
The review cautions that vitamin replacement is not fully preventive or restorative.
PMID:30358967 SUPPORT Other
"Vitamin A excess can be harmful to the developing fetus."
GeneReviews supports pregnancy-specific caution with high-dose vitamin A.
Essential fatty acid supplementation
Category: Therapeutic Action: nutritional supplementationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is nutritional supplementation, annotated with Nutritional Support (NCIT:C15433). NCIT:C15433 is a clinical intervention from the NCI Thesaurus. Ontology label: Nutritional Support NCIT:C15433
Small amounts of oils rich in polyunsaturated fatty acids can be used as tolerated to provide essential fatty acids despite overall dietary fat restriction.
Show evidence (2 references)
PMID:30358967 SUPPORT Other
"essential fatty acid supplementation (up to 1 teaspoon per day of oils rich in polyunsaturated fatty acids, as tolerated)"
GeneReviews recommends essential-fatty-acid supplementation as tolerated.
PMID:24288038 SUPPORT Other
"supplementation with essential fatty acids and high oral doses of fat soluble vitamins."
The management review lists essential fatty acids among treatment mainstays.
Multisystem surveillance
Category: Monitoring Action: supportive careNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is supportive care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. Ontology label: Supportive Care NCIT:C15747
Longitudinal follow-up assesses growth, blood count and reticulocytes, coagulation, liver tests and imaging, fat-soluble vitamins and related chemistries, lipids, and neurologic and ophthalmologic status. The intervals in GeneReviews provide a general evidence source rather than individualized medical instructions.
Show evidence (2 references)
PMID:30358967 SUPPORT Other
"Complete blood count, INR, reticulocyte count, liver function tests (AST, ALT, GGT, total and direct bilirubin, alkaline phosphatase, and albumin), fat-soluble vitamin levels"
GeneReviews specifies annual hematologic, coagulation, hepatic, and vitamin monitoring.
PMID:30358967 SUPPORT Other
"Ultrasound of the liver every three years. Ophthalmology and neurology evaluations every six to 12 months."
GeneReviews specifies periodic liver imaging and specialist neurologic and ophthalmologic review.
Genetic counseling and family evaluation
Category: Counseling / Informational Action: Genetic CounselingNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Genetic Counseling (NCIT:C15240). NCIT:C15240 is a clinical intervention from the NCI Thesaurus. NCIT:C15240
Counseling addresses autosomal-recessive recurrence risk, carrier testing, evaluation of at-risk siblings, and reproductive options when familial MTTP variants are known.
Show evidence (2 references)
PMID:30358967 SUPPORT Other
"At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier"
GeneReviews provides the autosomal-recessive recurrence-risk framework.
PMID:30358967 SUPPORT Other
"Carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible if the pathogenic MTTP variants in the family are known."
GeneReviews supports carrier and reproductive testing after familial-variant identification.
🔬

Biochemical Markers

2
Absent apoB-containing lipoproteins (DECREASED)
Context: ApoB-containing lipoproteins, including chylomicrons, VLDL, and LDL, are absent or virtually absent in plasma.
Show evidence (1 reference)
PMID:24288038 SUPPORT Other
"virtually absent apo B-containing lipoproteins, including chylomicrons, very low density lipoprotein and low density lipoprotein."
The review directly supports the defining plasma lipoprotein abnormality.
Low fat-soluble vitamin concentrations (DECREASED)
Context: Circulating vitamins A, D, and E are monitored because intestinal fat-soluble-vitamin absorption and transport are impaired; vitamin K deficiency is often assessed through coagulation measures.
Show evidence (4 references)
ORPHA:14 SUPPORT Other
"HP:0004905 | Low levels of vitamin A | Frequent (79-30%)"
Orphanet directly records low vitamin A concentrations.
ORPHA:14 SUPPORT Other
"HP:0100512 | Low levels of vitamin D | Frequent (79-30%)"
Orphanet directly records low vitamin D concentrations.
ORPHA:14 SUPPORT Other
"HP:0100513 | Low levels of vitamin E | Very frequent (99-80%)"
Orphanet directly records low vitamin E concentrations.
+ 1 more reference
🔬

Diagnosis

3
Plasma lipid and apoB measurement
Absent or extremely low LDL cholesterol, triglyceride, and apoB is the defining biochemical pattern and should prompt molecular testing. LDL-C and apoB below 15 mg/dL have been proposed as Japanese screening or eligibility thresholds, not as universal stand-alone diagnostic criteria.
blood chemistry measurement NCIT:C47868 NCI Thesaurus (NCIT)
Results: Absent or extremely low LDL cholesterol, triglyceride, and apoB strongly supports the diagnosis but does not distinguish MTTP-related ABL from all genetic mimics.
Show evidence (2 references)
PMID:30358967 SUPPORT Other
"absent or extremely low LDL-cholesterol, triglyceride, and apolipoprotein (apo) B levels"
GeneReviews defines the characteristic biochemical diagnostic pattern.
PMID:33994405 SUPPORT Other
"our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) ＜15 mg/dL and apoB ＜15 mg/dL can be useful in universal or opportunistic screening"
The review frames the numerical thresholds as screening or program-entry criteria rather than a universal molecular diagnosis.
Peripheral blood smear morphology
A peripheral blood smear can demonstrate acanthocytosis, a strong supportive clue in the appropriate severe-hypolipidemia and malabsorption phenotype.
clinical assessment NCIT:C124351 NCI Thesaurus (NCIT)
Results: Acanthocytosis supports the clinical diagnosis but is not a substitute for molecular confirmation.
Show evidence (1 reference)
PMID:24288038 SUPPORT Other
"Clinical diagnosis is based on signs and symptoms, acanthocytosis on blood smear, and virtually absent apo B-containing lipoproteins"
The review identifies acanthocytosis on smear as part of clinical diagnosis.
MTTP molecular genetic testing
Identification of biallelic pathogenic or likely pathogenic MTTP variants confirms MTTP-related abetalipoproteinemia in a patient with the compatible biochemical and clinical phenotype.
molecular genetic testing NCIT:C19770 NCI Thesaurus (NCIT)
Results: Biallelic pathogenic or likely pathogenic MTTP variants establish the molecular diagnosis.
Show evidence (1 reference)
PMID:30358967 SUPPORT Other
"biallelic pathogenic variants in MTTP identified by molecular genetic testing."
GeneReviews identifies biallelic MTTP variants found by molecular testing as the confirmatory criterion.
📈

Progression

3
Infancy
Age: Infancy
The usual untreated presentation is gastrointestinal, with steatorrhea, vomiting, fat malabsorption, and failure to thrive. Earlier recognition and nutritional treatment can substantially modify this course.
Show evidence (1 reference)
PMID:33994405 SUPPORT Other
"Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy."
The review identifies the characteristic infantile gastrointestinal and growth presentation.
Childhood to adolescence
Age: First to second decades
Persistent fat-soluble-vitamin deficiency can be followed by progressive neuromuscular disease, including loss of reflexes and proprioception, weakness, dysarthria, and ataxia.
Show evidence (1 reference)
PMID:30358967 SUPPORT Other
"dysarthria; and ataxia typically manifest in the first or second decades of life."
GeneReviews places the typical emergence of neuromuscular manifestations in the first two decades.
Adulthood and later life
Age: Adulthood onward
Untreated retinal disease may cause progressive loss of night and color vision in adulthood. Hepatic involvement is variable. High-dose vitamin replacement may delay complications and improve survival, but established dysfunction is not reliably reversed and complications can still occur.
Show evidence (3 references)
PMID:30358967 SUPPORT Other
"with progressive loss of night vision and/or color vision in adulthood."
GeneReviews supports adult progression of retinal visual dysfunction when disease is untreated.
PMID:33994405 SUPPORT Other
"High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis"
The review describes treatment-modified prognosis while avoiding a claim of cure.
PMID:33994405 SUPPORT Other
"However, it cannot fully prevent or restore impaired function."
The review explicitly cautions that vitamin replacement does not fully prevent or reverse established dysfunction.
📊

Prevalence

1
Worldwide
Point Prevalence ≤0.1 per 100,000 <1 in 1,000,000
Orphanet records Abetalipoproteinemia as an ultra-rare disorder with worldwide point prevalence below 1 per 1,000,000.
Show evidence (1 reference)
ORPHA:14 SUPPORT Other
"<1 / 1 000 000 | Worldwide | Point prevalence | PMID:30358967"
Orphanet provides a worldwide point-prevalence estimate below 1 per 1,000,000.
🔀

Differential Diagnoses

2

Conditions with similar clinical presentations that must be differentiated from Abetalipoproteinemia:

Familial hypobetalipoproteinemia 1 Not Yet Curated MONDO:0014252
Overlapping Features Severe biallelic APOB-related familial hypobetalipoproteinemia can be clinically and biochemically very similar to abetalipoproteinemia, but it is caused by APOB rather than MTTP variants.
Distinguishing Features
  • Biallelic pathogenic MTTP variants establish abetalipoproteinemia; biallelic APOB variants establish severe familial hypobetalipoproteinemia.
  • Obligate heterozygous parents usually have normal lipid levels in MTTP-related ABL but approximately half-normal apoB-containing lipoproteins in severe APOB-related disease.
Show evidence (3 references)
PMID:24288038 SUPPORT Other
"mutations either in both alleles of the MTP (alias MTTP) gene encoding microsomal triglyceride transfer protein (MTP) or both alleles of the APOB gene itself in the case of ABL and HHBL, respectively."
The review distinguishes the two phenocopies by their causal genes.
PMID:24288038 SUPPORT Other
"Obligate heterozygote parents of ABL patients usually have normal lipids"
The review supplies a useful family-lipid discriminator.
PMID:36243606 SUPPORT Other
"we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease"
Contemporary guidance treats these as related but distinct monogenic hypolipidemia disorders.
Chylomicron retention disease Not Yet Curated MONDO:0009528
Overlapping Features SAR1B-related chylomicron retention disease also causes early fat malabsorption, hypocholesterolemia, and fat-soluble-vitamin deficiency, but the defect is ER-to-Golgi transport of chylomicron cargo rather than MTTP-dependent apoB-particle lipidation and assembly.
Distinguishing Features
  • Biallelic MTTP variants favor abetalipoproteinemia, whereas biallelic SAR1B variants favor chylomicron retention disease.
  • Postprandial absence of chylomicrons and apoB48 with a SAR1B/COPII transport defect supports chylomicron retention disease.
Show evidence (2 references)
PMID:30640893 SUPPORT Other
"CRD patients present with SAR1B mutations, which disable the formation of coat protein complex II and thus blocks the transport of chylomicron cargo from the endoplasmic reticulum to the Golgi."
The review identifies the distinct SAR1B/COPII transport mechanism.
PMID:30640893 SUPPORT Other
"Molecular testing for CRD is recommended to distinguish the disease from other congenital fat malabsorptions"
The review explicitly recommends molecular testing to distinguish this phenocopy.
{ }

Source YAML

click to show 
name: Abetalipoproteinemia
creation_date: '2026-05-04T05:21:52Z'
category: Mendelian
description: >
  Abetalipoproteinemia is a severe autosomal recessive disorder of
  apoB-containing lipoprotein assembly and secretion caused by biallelic MTTP
  pathogenic variants. Loss of microsomal triglyceride transfer protein
  function prevents normal chylomicron export from enterocytes and VLDL export
  from hepatocytes, producing absent or extremely low apoB-containing
  lipoproteins, hypocholesterolemia, hypotriglyceridemia, fat malabsorption,
  and secondary fat-soluble vitamin deficiency. Infants typically present with
  failure to thrive, diarrhea, vomiting, steatorrhea, acanthocytosis, and
  abnormal lipid studies; untreated individuals can later develop retinal,
  neurologic, hematologic, hepatic, and coagulation complications. Management
  centers on a low-fat diet, essential fatty acid intake, and high-dose
  fat-soluble vitamin supplementation.
disease_term:
  preferred_term: abetalipoproteinemia
  term:
    id: MONDO:0008692
    label: abetalipoproteinemia
notes: >-
  This entry is restricted to MTTP-related abetalipoproteinemia. Orphanet's
  historical record also uses "homozygous familial hypobetalipoproteinemia" as
  a synonym and lists several broader OMIM cross-references, but biallelic
  APOB-related familial hypobetalipoproteinemia is a distinct disorder and is
  represented below as a differential diagnosis rather than as an identity.
synonyms:
- Bassen-Kornzweig disease
- ABL
- MTP deficiency
parents:
- Hypobetalipoproteinemia
classifications:
  harrisons_chapter:
  - classification_value: GENETICS_ENVIRONMENT_DISEASE
    evidence:
    - reference: PMID:33994405
      reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by"
      explanation: The review supports classification as a Mendelian genetic disorder.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0008692
      label: abetalipoproteinemia
    mapping_predicate: skos:exactMatch
    mapping_source: Orphanet ORPHA:14
    mapping_justification: >-
      The structured Orphanet record lists MONDO:0008692 as an exact
      cross-reference for abetalipoproteinemia.
inheritance:
- name: Autosomal Recessive
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Autosomal recessive"
    explanation: Orphanet classifies Abetalipoproteinemia inheritance as autosomal recessive.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "inherited in an autosomal recessive"
    explanation: GeneReviews states that abetalipoproteinemia is inherited in an autosomal recessive manner.
prevalence:
- population: Worldwide
  measure_type: POINT_PREVALENCE
  prevalence_class: BELOW_1_IN_1000000
  rate_high: 0.1
  notes: >-
    Orphanet records Abetalipoproteinemia as an ultra-rare disorder with
    worldwide point prevalence below 1 per 1,000,000.
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "<1 / 1 000 000 | Worldwide | Point prevalence | PMID:30358967"
    explanation: Orphanet provides a worldwide point-prevalence estimate below 1 per 1,000,000.
progression:
- phase: Infancy
  age_range: Infancy
  notes: >-
    The usual untreated presentation is gastrointestinal, with steatorrhea,
    vomiting, fat malabsorption, and failure to thrive. Earlier recognition and
    nutritional treatment can substantially modify this course.
  evidence:
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy."
    explanation: The review identifies the characteristic infantile gastrointestinal and growth presentation.
- phase: Childhood to adolescence
  age_range: First to second decades
  notes: >-
    Persistent fat-soluble-vitamin deficiency can be followed by progressive
    neuromuscular disease, including loss of reflexes and proprioception,
    weakness, dysarthria, and ataxia.
  evidence:
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "dysarthria; and ataxia typically manifest in the first or second decades of life."
    explanation: GeneReviews places the typical emergence of neuromuscular manifestations in the first two decades.
- phase: Adulthood and later life
  age_range: Adulthood onward
  notes: >-
    Untreated retinal disease may cause progressive loss of night and color
    vision in adulthood. Hepatic involvement is variable. High-dose vitamin
    replacement may delay complications and improve survival, but established
    dysfunction is not reliably reversed and complications can still occur.
  evidence:
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "with progressive loss of night vision and/or color vision in adulthood."
    explanation: GeneReviews supports adult progression of retinal visual dysfunction when disease is untreated.
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis"
    explanation: The review describes treatment-modified prognosis while avoiding a claim of cure.
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "However, it cannot fully prevent or restore impaired function."
    explanation: The review explicitly cautions that vitamin replacement does not fully prevent or reverse established dysfunction.
mechanistic_hypotheses:
- hypothesis_group_id: canonical_mttp_lipoprotein_assembly_model
  hypothesis_label: Canonical MTTP ApoB-Lipoprotein Assembly Model
  status: CANONICAL
  description: >-
    Biallelic MTTP loss of function disrupts the microsomal triglyceride
    transfer protein complex and prevents normal assembly and secretion of
    intestinal apoB48-containing chylomicrons and hepatic apoB100-containing
    VLDL. The resulting absence of apoB lipoproteins produces severe
    hypolipidemia, intestinal fat and fat-soluble-vitamin malabsorption, hepatic
    triglyceride retention, and downstream multisystem complications.
  notes: >-
    The proximal MTTP-to-apoB-assembly mechanism is established. The detailed
    intermediates linking apoB-lipoprotein absence to acanthocyte formation
    remain incompletely resolved, and this entry does not treat retinal MTTP
    expression or single hypomorphic cases as established alternative disease
    mechanisms or genotype-phenotype rules.
  evidence:
  - reference: PMID:1439810
    reference_title: Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MTP activity and the 88-kilodalton component of MTP were present in intestinal biopsy samples from eight control individuals but were absent in four abetalipoproteinemic subjects."
    explanation: Human intestinal-biopsy data directly demonstrate absent MTP protein and activity in affected individuals.
  - reference: PMID:7782284
    reference_title: A 30-amino acid truncation of the microsomal triglyceride transfer protein large subunit disrupts its interaction with protein disulfide-isomerase and causes abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "only the normal subunit was able to form a stable, soluble complex with protein disulfide-isomerase"
    explanation: Functional reconstitution shows that a disease-associated truncation disrupts the MTP-PDI complex.
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver"
    explanation: The contemporary review states the canonical proximal mechanism in the affected intestinal and hepatic compartments.
pathophysiology:
- name: MTTP Loss of Function
  description: >-
    Biallelic pathogenic MTTP variants reduce or abolish microsomal
    triglyceride transfer protein activity. MTP normally forms a lipid-transfer
    complex with protein disulfide isomerase; loss of the functional complex
    prevents normal lipidation of nascent apoB.
  role: trigger
  gene:
    preferred_term: MTTP
    term:
      id: hgnc:7467
      label: MTTP
  molecular_functions:
  - preferred_term: lipid transfer activity
    term:
      id: GO:0120013
      label: lipid transfer activity
    modifier: DECREASED
  - preferred_term: apolipoprotein binding
    term:
      id: GO:0034185
      label: apolipoprotein binding
    modifier: DECREASED
  biological_processes:
  - preferred_term: triglyceride transport
    term:
      id: GO:0034197
      label: triglyceride transport
    modifier: DECREASED
  - preferred_term: lipoprotein metabolic process
    term:
      id: GO:0042157
      label: lipoprotein metabolic process
    modifier: DECREASED
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MTTP | microsomal triglyceride transfer protein | hgnc:7467 | Disease-causing germline mutation(s) in"
    explanation: Orphanet records MTTP as the disease-causing gene.
  - reference: PMID:1439810
    reference_title: Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MTP activity and the 88-kilodalton component of MTP were present in intestinal biopsy samples from eight control individuals but were absent in four abetalipoproteinemic subjects."
    explanation: Human intestinal biopsies directly demonstrate absent MTP protein and activity.
  - reference: PMID:7782284
    reference_title: A 30-amino acid truncation of the microsomal triglyceride transfer protein large subunit disrupts its interaction with protein disulfide-isomerase and causes abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "only the normal subunit was able to form a stable, soluble complex with protein disulfide-isomerase"
    explanation: Functional reconstitution shows disruption of the required MTP-PDI complex by a patient-derived truncation.
  downstream:
  - target: Defective ApoB Lipidation and Particle Assembly
    description: Loss of MTP lipid-transfer activity prevents normal lipidation and assembly of nascent apoB-containing particles.
    causal_link_type: DIRECT
    hypothesis_groups:
    - canonical_mttp_lipoprotein_assembly_model
    evidence:
    - reference: PMID:33994405
      reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver"
      explanation: The review directly links MTP deficiency to failed intestinal and hepatic apoB-particle assembly.
- name: Defective ApoB Lipidation and Particle Assembly
  description: >-
    MTP deficiency prevents the lipidation and assembly of apoB48-containing
    chylomicrons in enterocytes and apoB100-containing VLDL particles in
    hepatocytes.
  role: mediator
  biological_processes:
  - preferred_term: chylomicron assembly
    term:
      id: GO:0034378
      label: chylomicron assembly
    modifier: DECREASED
  - preferred_term: very-low-density lipoprotein particle assembly
    term:
      id: GO:0034379
      label: very-low-density lipoprotein particle assembly
    modifier: DECREASED
  cell_types:
  - preferred_term: enterocyte
    term:
      id: CL:0000584
      label: enterocyte
  - preferred_term: hepatocyte
    term:
      id: CL:0000182
      label: hepatocyte
  evidence:
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver"
    explanation: The review supports failed apoB-particle assembly in both affected tissues.
  downstream:
  - target: Failed Chylomicron and VLDL Secretion
    description: Particles that cannot be assembled and lipidated are not normally secreted from enterocytes or hepatocytes.
    causal_link_type: DIRECT
    hypothesis_groups:
    - canonical_mttp_lipoprotein_assembly_model
    evidence:
    - reference: PMID:24288038
      reference_title: "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "The root cause of both disorders is improper packaging and secretion of apolipoprotein (apo) B-containing lipoprotein particles"
      explanation: The review identifies defective packaging and secretion of apoB-containing particles as the shared proximal defect.
- name: Failed Chylomicron and VLDL Secretion
  description: >-
    Failed secretion of intestinal chylomicrons and hepatic VLDL leaves
    apoB-containing lipoproteins virtually absent from plasma, impairs dietary
    lipid transport, and prevents normal export of hepatic triglyceride.
  role: mediator
  biological_processes:
  - preferred_term: lipid transport
    term:
      id: GO:0006869
      label: lipid transport
    modifier: DECREASED
  cell_types:
  - preferred_term: enterocyte
    term:
      id: CL:0000584
      label: enterocyte
  - preferred_term: hepatocyte
    term:
      id: CL:0000182
      label: hepatocyte
  evidence:
  - reference: PMID:24288038
    reference_title: "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "virtually absent apo B-containing lipoproteins, including chylomicrons, very low density lipoprotein and low density lipoprotein."
    explanation: The review supports the characteristic absence of chylomicrons, VLDL, and LDL.
  downstream:
  - target: Impaired Intestinal Lipid Absorption
    description: Absent intestinal chylomicron export disrupts absorption and transport of dietary lipid.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - absent apoB48-containing chylomicron export from enterocytes
    hypothesis_groups:
    - canonical_mttp_lipoprotein_assembly_model
    evidence:
    - reference: PMID:33994405
      reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia."
      explanation: The review links failed apoB-particle assembly to fat malabsorption.
  - target: Absent apoB-containing lipoproteins
    description: Failed chylomicron and VLDL secretion is measured as absent or extremely low circulating apoB-containing lipoproteins.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:24288038
      reference_title: "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "virtually absent apo B-containing lipoproteins, including chylomicrons, very low density lipoprotein and low density lipoprotein."
      explanation: The review directly supports this biochemical consequence.
  - target: Abnormal circulating apolipoprotein concentration
    description: Circulating apoB is absent or extremely low.
    causal_link_type: DIRECT
  - target: Hypocholesterolemia
    description: Loss of apoB-containing particles produces severe hypocholesterolemia.
    causal_link_type: DIRECT
  - target: Decreased LDL cholesterol concentration
    description: LDL cholesterol is absent or extremely low because its apoB-containing precursors are not secreted normally.
    causal_link_type: DIRECT
  - target: Decreased HDL cholesterol concentration
    description: HDL cholesterol can also be decreased, although the intervening mechanism is not resolved here.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Hypotriglyceridemia
    description: Loss of chylomicron and VLDL secretion produces extremely low circulating triglyceride.
    causal_link_type: DIRECT
  - target: Acanthocytosis and Hemolysis
    description: ApoB-lipoprotein absence is accompanied by acanthocytosis and hemolytic findings, but the detailed membrane-lipid intermediates remain incompletely resolved.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_mttp_lipoprotein_assembly_model
  - target: Hepatic Triglyceride Retention
    description: Impaired hepatic VLDL export retains triglyceride in hepatocytes.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - failure to export triglyceride in apoB100-containing VLDL
    hypothesis_groups:
    - canonical_mttp_lipoprotein_assembly_model
    evidence:
    - reference: PMID:32039990
      reference_title: "Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Fatty liver, cirrhosis and hepatocellular carcinoma have been reported in FHBL and ABL probably due to decreased triglyceride export from the liver."
      explanation: The liver review supports decreased triglyceride export as the likely link to hepatic lipid accumulation.
- name: Impaired Intestinal Lipid Absorption
  description: >-
    Failure to export chylomicrons from enterocytes impairs absorption and
    transport of dietary fat, causing steatorrhea, gastrointestinal symptoms,
    inadequate caloric utilization, and early growth failure.
  role: mediator
  biological_processes:
  - preferred_term: intestinal lipid absorption
    term:
      id: GO:0098856
      label: intestinal lipid absorption
    modifier: DECREASED
  cell_types:
  - preferred_term: enterocyte
    term:
      id: CL:0000584
      label: enterocyte
  evidence:
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy."
    explanation: The review identifies the characteristic clinical consequences of the intestinal branch.
  downstream:
  - target: Fat malabsorption
    description: Defective chylomicron export produces impaired dietary fat absorption.
    causal_link_type: DIRECT
  - target: Steatorrhea
    description: Unabsorbed dietary fat produces steatorrhea.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - excess unabsorbed intestinal fat
  - target: Chronic diarrhea
    description: Intestinal fat malabsorption contributes to chronic diarrhea.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - unabsorbed intestinal lipid and increased stool losses
  - target: Vomiting
    description: Vomiting is part of the characteristic infantile gastrointestinal presentation.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Failure to thrive
    description: Reduced absorption of dietary calories contributes to early growth failure.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - inadequate caloric absorption
  - target: Reduced Fat-Soluble Vitamin Bioavailability
    description: Chylomicron failure impairs absorption and transport of vitamins A, D, E, and K.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - impaired intestinal uptake and transport of fat-soluble vitamins
    hypothesis_groups:
    - canonical_mttp_lipoprotein_assembly_model
    evidence:
    - reference: PMID:33994405
      reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia."
      explanation: The review directly supports fat-soluble-vitamin malabsorption downstream of the apoB-particle defect.
- name: Reduced Fat-Soluble Vitamin Bioavailability
  description: >-
    Impaired absorption and lipoprotein transport reduce the bioavailability of
    vitamins A, D, E, and K. Tissue deficiency drives retinal, neurologic,
    skeletal, and coagulation complications.
  role: mediator
  evidence:
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia."
    explanation: The review supports reduced fat-soluble-vitamin bioavailability downstream of the MTTP defect.
  downstream:
  - target: Reduced circulating vitamin A concentration
    description: Reduced vitamin A absorption and transport lowers circulating vitamin A.
    causal_link_type: DIRECT
  - target: Decreased circulating vitamin D concentration
    description: Reduced vitamin D absorption and transport lowers circulating vitamin D.
    causal_link_type: DIRECT
  - target: Decreased circulating vitamin E concentration
    description: Reduced vitamin E absorption and transport lowers circulating vitamin E.
    causal_link_type: DIRECT
  - target: Low fat-soluble vitamin concentrations
    description: The combined vitamin-deficiency state is measurable in blood.
    causal_link_type: DIRECT
  - target: Osteopenia
    description: Reduced vitamin D bioavailability can contribute to reduced bone density.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - reduced vitamin D availability
  - target: Vitamin A/E-Associated Retinal Degeneration
    description: Chronic vitamin A and E deficiency contributes to progressive retinal degeneration.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - inadequate vitamin delivery to retinal tissues
    hypothesis_groups:
    - canonical_mttp_lipoprotein_assembly_model
    evidence:
    - reference: PMID:26086616
      reference_title: Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "later in life, with progressive ophthalmopathy and neuropathy as a result of deficiency of the fat-soluble vitamins A and E."
      explanation: The review attributes later retinal disease to vitamin A and E deficiency.
  - target: Vitamin E-Associated Neuromuscular Injury
    description: Chronic vitamin E deficiency contributes to progressive neuropathy and myopathy.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - inadequate vitamin E delivery to neural and muscle tissues
    hypothesis_groups:
    - canonical_mttp_lipoprotein_assembly_model
    evidence:
    - reference: PMID:26086616
      reference_title: Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "later in life, with progressive ophthalmopathy and neuropathy as a result of deficiency of the fat-soluble vitamins A and E."
      explanation: The review attributes later neuropathy to fat-soluble-vitamin deficiency.
  - target: Vitamin K-Related Coagulopathy
    description: Reduced vitamin K bioavailability impairs normal coagulation.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - reduced vitamin-K-dependent coagulation activity
    hypothesis_groups:
    - canonical_mttp_lipoprotein_assembly_model
    evidence:
    - reference: PMID:30358967
      reference_title: Abetalipoproteinemia.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Malabsorption of fat-soluble vitamins (A, D, E, and K) can result in an increased international normalized ratio (INR)."
      explanation: GeneReviews links fat-soluble-vitamin malabsorption to abnormal coagulation.
- name: Vitamin A/E-Associated Retinal Degeneration
  description: >-
    Chronic vitamin A and E deficiency is associated with progressive retinal
    degeneration, abnormal retinal pigmentation, night and color vision loss,
    and eventual severe visual impairment. The entry does not assume a separate
    tissue-autonomous MTTP mechanism.
  role: mediator
  evidence:
  - reference: PMID:26086616
    reference_title: Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "later in life, with progressive ophthalmopathy and neuropathy as a result of deficiency of the fat-soluble vitamins A and E."
    explanation: The review supports the vitamin-deficiency retinal branch.
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Untreated individuals may develop atypical pigmentation of the retina"
    explanation: GeneReviews describes untreated retinal pigmentation and progressive visual dysfunction.
  downstream:
  - target: Progressive visual loss
    description: Progressive retinal dysfunction causes worsening visual loss.
    causal_link_type: DIRECT
  - target: Rod-cone dystrophy
    description: Retinal degeneration can present with a rod-cone dystrophy pattern.
    causal_link_type: DIRECT
  - target: Color vision defect
    description: Progressive retinal dysfunction can impair color vision.
    causal_link_type: DIRECT
  - target: Nyctalopia
    description: Rod-predominant retinal dysfunction causes night blindness.
    causal_link_type: DIRECT
  - target: Abnormal retinal pigmentation
    description: Untreated retinal degeneration can produce abnormal retinal pigmentation.
    causal_link_type: DIRECT
- name: Vitamin E-Associated Neuromuscular Injury
  description: >-
    Chronic vitamin E deficiency is associated with progressive peripheral
    neuropathy, posterior-column sensory dysfunction, loss of reflexes,
    weakness, myopathy, dysarthria, and ataxia.
  role: mediator
  evidence:
  - reference: PMID:26086616
    reference_title: Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "later in life, with progressive ophthalmopathy and neuropathy as a result of deficiency of the fat-soluble vitamins A and E."
    explanation: The review supports vitamin-deficiency-associated neuropathy.
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "deep tendon reflexes, vibratory sense, and proprioception; muscle weakness; dysarthria; and ataxia typically manifest"
    explanation: GeneReviews describes the characteristic neuromuscular manifestations.
  downstream:
  - target: Areflexia
    description: Progressive neurologic disease can cause loss of deep tendon reflexes.
    causal_link_type: DIRECT
  - target: Ataxia
    description: Sensory and neuromuscular dysfunction can produce ataxia.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - posterior-column and peripheral-nerve dysfunction
  - target: Dysarthria
    description: Progressive neuromuscular involvement can cause dysarthria.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Impaired vibratory sensation
    description: Posterior-column and sensory-nerve dysfunction impairs vibration sense.
    causal_link_type: DIRECT
  - target: Impaired proprioception
    description: Posterior-column and sensory-nerve dysfunction impairs proprioception.
    causal_link_type: DIRECT
  - target: Peripheral neuropathy
    description: Vitamin-deficiency-associated injury can produce progressive peripheral neuropathy.
    causal_link_type: DIRECT
  - target: Myopathy
    description: Neuromuscular involvement can include myopathy.
    causal_link_type: DIRECT
  - target: Muscle weakness
    description: Neuropathy and myopathy can cause progressive muscle weakness.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - peripheral neuropathy and myopathy
  - target: Pes cavus
    description: Chronic peripheral neuromuscular disease can be accompanied by pes cavus.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
- name: Acanthocytosis and Hemolysis
  description: >-
    Abetalipoproteinemia is accompanied by acanthocytic erythrocyte morphology
    and can include anemia, reticulocytosis, hemolysis, and secondary
    hyperbilirubinemia. The detailed membrane-lipid pathway from apoB-particle
    absence to acanthocyte formation remains incompletely resolved.
  role: mediator
  cell_types:
  - preferred_term: erythrocyte
    term:
      id: CL:0000232
      label: erythrocyte
  evidence:
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Hematologic manifestations may include acanthocytosis (irregularly spiculated erythrocytes), anemia, reticulocytosis, and hemolysis with resultant hyperbilirubinemia."
    explanation: GeneReviews directly supports the linked hematologic manifestation set.
  downstream:
  - target: Acanthocytosis
    description: Altered erythrocyte morphology is observed as acanthocytosis.
    causal_link_type: DIRECT
  - target: Anemia
    description: Hemolysis can contribute to anemia.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - shortened erythrocyte survival
  - target: Reticulocytosis
    description: Compensatory erythropoiesis can produce reticulocytosis.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - increased erythropoietic response to hemolysis
  - target: Hyperbilirubinemia
    description: Erythrocyte destruction increases bilirubin production.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - heme catabolism after hemolysis
- name: Vitamin K-Related Coagulopathy
  description: >-
    Vitamin K deficiency secondary to fat-soluble-vitamin malabsorption can
    increase the international normalized ratio or prolong prothrombin time and
    can manifest clinically as bleeding.
  role: mediator
  evidence:
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Malabsorption of fat-soluble vitamins (A, D, E, and K) can result in an increased international normalized ratio (INR)."
    explanation: GeneReviews links fat-soluble-vitamin malabsorption to increased INR.
  downstream:
  - target: Prolonged prothrombin time
    description: Reduced vitamin-K-dependent coagulation activity prolongs prothrombin time.
    causal_link_type: DIRECT
  - target: Abnormal bleeding
    description: Clinically significant coagulopathy can produce abnormal bleeding.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - impaired vitamin-K-dependent coagulation
- name: Hepatic Triglyceride Retention
  description: >-
    Failure to export triglyceride in apoB100-containing VLDL promotes lipid
    retention in hepatocytes. Steatosis is variably expressed and can rarely
    progress to fibrosis or cirrhosis.
  role: mediator
  cell_types:
  - preferred_term: hepatocyte
    term:
      id: CL:0000182
      label: hepatocyte
  biological_processes:
  - preferred_term: lipid storage
    term:
      id: GO:0019915
      label: lipid storage
    modifier: INCREASED
  evidence:
  - reference: PMID:32039990
    reference_title: "Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Fatty liver, cirrhosis and hepatocellular carcinoma have been reported in FHBL and ABL probably due to decreased triglyceride export from the liver."
    explanation: The review supports hepatic triglyceride-export failure as the likely mechanism of liver disease.
  - reference: PMID:24842304
    reference_title: Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "They suggest that the genetic defect in VLDL assembly is critical for the occurrence of liver steatosis leading to fibrosis"
    explanation: A human ABL/FHBL cohort supports the VLDL-assembly defect as critical to steatosis and fibrosis.
  downstream:
  - target: Hepatomegaly
    description: Hepatic lipid accumulation can enlarge the liver.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - hepatocyte lipid accumulation
  - target: Hepatic steatosis
    description: Hepatocyte triglyceride retention is observed as hepatic steatosis.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:24288038
      reference_title: "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "neuropathy and coagulopathy. Hepatic steatosis is also common."
      explanation: The review directly supports hepatic steatosis as a common ABL manifestation.
  - target: Hepatic fibrosis
    description: Chronic hepatic injury can progress to fibrosis.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - chronic hepatocyte injury and fibrogenic activation
  - target: Cirrhosis
    description: Advanced chronic hepatic injury can rarely progress to cirrhosis.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - progressive hepatic fibrosis
  - target: Hypoalbuminemia
    description: Hepatic or nutritional involvement can be accompanied by hypoalbuminemia.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
phenotypes:
- name: Abnormal circulating apolipoprotein concentration
  category: Biochemical
  frequency: VERY_FREQUENT
  description: Circulating apoB-containing lipoproteins are absent or extremely low.
  phenotype_term:
    preferred_term: Abnormal circulating apolipoprotein concentration
    term:
      id: HP:0025201
      label: Abnormal circulating apolipoprotein concentration
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0025201 | Abnormal circulating apolipoprotein concentration | Very frequent (99-80%)"
    explanation: Orphanet records abnormal circulating apolipoprotein concentration as very frequent.
- name: Hypocholesterolemia
  category: Biochemical
  frequency: FREQUENT
  description: Total cholesterol is markedly decreased because apoB lipoproteins are absent or extremely low.
  phenotype_term:
    preferred_term: Hypocholesterolemia
    term:
      id: HP:0003146
      label: Hypocholesterolemia
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003146 | Hypocholesterolemia | Frequent (79-30%)"
    explanation: Orphanet records hypocholesterolemia as frequent.
  - reference: PMID:24288038
    reference_title: "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "are rare diseases characterized by hypocholesterolemia and"
    explanation: This review describes hypocholesterolemia as a core feature.
- name: Decreased LDL cholesterol concentration
  category: Biochemical
  frequency: FREQUENT
  description: LDL cholesterol is absent or extremely low.
  phenotype_term:
    preferred_term: Decreased LDL cholesterol concentration
    term:
      id: HP:0003563
      label: Decreased LDL cholesterol concentration
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003563 | Decreased LDL cholesterol concentration | Frequent (79-30%)"
    explanation: Orphanet records decreased LDL cholesterol concentration as frequent.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "proband with absent or extremely low LDL-cholesterol, triglyceride, and"
    explanation: GeneReviews describes absent or extremely low LDL cholesterol as a diagnostic biochemical feature.
- name: Decreased HDL cholesterol concentration
  category: Biochemical
  frequency: FREQUENT
  description: HDL cholesterol can be decreased in Abetalipoproteinemia.
  phenotype_term:
    preferred_term: Decreased HDL cholesterol concentration
    term:
      id: HP:0003233
      label: Decreased HDL cholesterol concentration
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003233 | Decreased HDL cholesterol concentration | Frequent (79-30%)"
    explanation: Orphanet records decreased HDL cholesterol concentration as frequent.
- name: Hypotriglyceridemia
  category: Biochemical
  frequency: FREQUENT
  description: Plasma triglycerides are very low due to loss of chylomicron and VLDL export.
  phenotype_term:
    preferred_term: Hypotriglyceridemia
    term:
      id: HP:0012153
      label: Hypotriglyceridemia
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012153 | Hypotriglyceridemia | Frequent (79-30%)"
    explanation: Orphanet records hypotriglyceridemia as frequent.
- name: Fat malabsorption
  category: Gastrointestinal
  frequency: VERY_FREQUENT
  description: Intestinal lipid absorption is impaired.
  phenotype_term:
    preferred_term: Fat malabsorption
    term:
      id: HP:0002630
      label: Fat malabsorption
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002630 | Fat malabsorption | Very frequent (99-80%)"
    explanation: Orphanet records fat malabsorption as very frequent.
- name: Steatorrhea
  category: Gastrointestinal
  frequency: VERY_FREQUENT
  description: Fat malabsorption causes fatty stools.
  phenotype_term:
    preferred_term: Steatorrhea
    term:
      id: HP:0002570
      label: Steatorrhea
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002570 | Steatorrhea | Very frequent (99-80%)"
    explanation: Orphanet records steatorrhea as very frequent.
- name: Chronic diarrhea
  category: Gastrointestinal
  frequency: FREQUENT
  description: Chronic diarrhea is a common early manifestation.
  phenotype_term:
    preferred_term: Chronic diarrhea
    term:
      id: HP:0002028
      label: Chronic diarrhea
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002028 | Chronic diarrhea | Frequent (79-30%)"
    explanation: Orphanet records chronic diarrhea as frequent.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "with failure to thrive, diarrhea, vomiting, and malabsorption of fat."
    explanation: GeneReviews supports diarrhea as part of the typical infant presentation.
- name: Vomiting
  category: Gastrointestinal
  frequency: OCCASIONAL
  description: Vomiting is part of the characteristic infantile gastrointestinal presentation.
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002013 | Vomiting | Occasional (29-5%)"
    explanation: Orphanet records vomiting as an occasional phenotype.
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy."
    explanation: The review identifies vomiting as part of the typical infantile presentation.
- name: Failure to thrive
  category: Growth
  frequency: FREQUENT
  description: Infants may have poor weight gain and growth failure.
  phenotype_term:
    preferred_term: Failure to thrive
    term:
      id: HP:0001508
      label: Failure to thrive
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001508 | Failure to thrive | Frequent (79-30%)"
    explanation: Orphanet records failure to thrive as frequent.
- name: Reduced circulating vitamin A concentration
  category: Biochemical
  frequency: FREQUENT
  description: Vitamin A is reduced due to fat-soluble vitamin malabsorption.
  phenotype_term:
    preferred_term: Reduced circulating vitamin A concentration
    term:
      id: HP:0004905
      label: Reduced circulating vitamin A concentration
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0004905 | Low levels of vitamin A | Frequent (79-30%)"
    explanation: Orphanet records low vitamin A levels as frequent.
- name: Decreased circulating vitamin D concentration
  category: Biochemical
  frequency: FREQUENT
  description: Vitamin D is reduced due to fat-soluble vitamin malabsorption.
  phenotype_term:
    preferred_term: Decreased circulating vitamin D concentration
    term:
      id: HP:0100512
      label: Decreased circulating vitamin D concentration
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0100512 | Low levels of vitamin D | Frequent (79-30%)"
    explanation: Orphanet records low vitamin D levels as frequent.
- name: Osteopenia
  category: Musculoskeletal
  frequency: OCCASIONAL
  description: Reduced bone density can occur in association with fat-soluble vitamin malabsorption.
  phenotype_term:
    preferred_term: Osteopenia
    term:
      id: HP:0000938
      label: Osteopenia
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000938 | Osteopenia | Occasional (29-5%)"
    explanation: Orphanet records osteopenia as an occasional phenotype.
- name: Decreased circulating vitamin E concentration
  category: Biochemical
  frequency: VERY_FREQUENT
  description: Vitamin E is reduced and contributes to retinal and neurologic complications when untreated.
  phenotype_term:
    preferred_term: Decreased circulating vitamin E concentration
    term:
      id: HP:0100513
      label: Decreased circulating vitamin E concentration
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0100513 | Low levels of vitamin E | Very frequent (99-80%)"
    explanation: Orphanet records low vitamin E levels as very frequent.
- name: Acanthocytosis
  category: Hematologic
  frequency: VERY_FREQUENT
  description: Blood smears show acanthocytes.
  phenotype_term:
    preferred_term: Acanthocytosis
    term:
      id: HP:0001927
      label: Acanthocytosis
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001927 | Acanthocytosis | Very frequent (99-80%)"
    explanation: Orphanet records acanthocytosis as very frequent.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Hematologic manifestations may include acanthocytosis (irregularly spiculated"
    explanation: GeneReviews supports acanthocytosis as a hematologic manifestation.
- name: Anemia
  category: Hematologic
  frequency: FREQUENT
  description: Anemia can occur as part of hematologic involvement.
  phenotype_term:
    preferred_term: Anemia
    term:
      id: HP:0001903
      label: Anemia
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001903 | Anemia | Frequent (79-30%)"
    explanation: Orphanet records anemia as frequent.
- name: Reticulocytosis
  category: Hematologic
  frequency: FREQUENT
  description: Reticulocytosis can accompany hemolysis.
  phenotype_term:
    preferred_term: Reticulocytosis
    term:
      id: HP:0001923
      label: Reticulocytosis
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001923 | Reticulocytosis | Frequent (79-30%)"
    explanation: Orphanet records reticulocytosis as frequent.
- name: Hyperbilirubinemia
  category: Biochemical
  frequency: FREQUENT
  description: Hyperbilirubinemia may result from hemolysis.
  phenotype_term:
    preferred_term: Hyperbilirubinemia
    term:
      id: HP:0002904
      label: Hyperbilirubinemia
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002904 | Hyperbilirubinemia | Frequent (79-30%)"
    explanation: Orphanet records hyperbilirubinemia as frequent.
- name: Hypoalbuminemia
  category: Biochemical
  frequency: FREQUENT
  description: Low serum albumin is recorded among frequent Orphanet phenotypes.
  phenotype_term:
    preferred_term: Hypoalbuminemia
    term:
      id: HP:0003073
      label: Hypoalbuminemia
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003073 | Hypoalbuminemia | Frequent (79-30%)"
    explanation: Orphanet records hypoalbuminemia as frequent.
- name: Areflexia
  category: Neurologic
  frequency: FREQUENT
  description: Deep tendon reflexes can be reduced or absent.
  phenotype_term:
    preferred_term: Areflexia
    term:
      id: HP:0001284
      label: Areflexia
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001284 | Areflexia | Frequent (79-30%)"
    explanation: Orphanet records areflexia as frequent.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "deep tendon reflexes, vibratory sense, and proprioception; muscle weakness;"
    explanation: GeneReviews describes progressive loss of deep tendon reflexes in untreated individuals.
- name: Ataxia
  category: Neurologic
  frequency: OCCASIONAL
  description: Ataxia can occur as part of untreated neurologic involvement.
  phenotype_term:
    preferred_term: Ataxia
    term:
      id: HP:0001251
      label: Ataxia
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001251 | Ataxia | Occasional (29-5%)"
    explanation: Orphanet records ataxia as an occasional phenotype.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "dysarthria; and ataxia typically manifest"
    explanation: GeneReviews describes ataxia among neuromuscular findings in untreated individuals.
- name: Dysarthria
  category: Neurologic
  frequency: OCCASIONAL
  description: Dysarthria can occur as part of neurologic involvement.
  phenotype_term:
    preferred_term: Dysarthria
    term:
      id: HP:0001260
      label: Dysarthria
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001260 | Dysarthria | Occasional (29-5%)"
    explanation: Orphanet records dysarthria as an occasional phenotype.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "dysarthria; and ataxia typically manifest"
    explanation: GeneReviews describes dysarthria among neuromuscular findings in untreated individuals.
- name: Impaired vibratory sensation
  category: Neurologic
  frequency: OCCASIONAL
  description: Posterior column involvement can reduce vibration sense.
  phenotype_term:
    preferred_term: Impaired vibratory sensation
    term:
      id: HP:0002495
      label: Impaired vibratory sensation
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002495 | Impaired vibratory sensation | Occasional (29-5%)"
    explanation: Orphanet records impaired vibratory sensation as an occasional phenotype.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "deep tendon reflexes, vibratory sense, and proprioception; muscle weakness;"
    explanation: GeneReviews describes progressive loss of vibratory sense in untreated individuals.
- name: Impaired proprioception
  category: Neurologic
  frequency: OCCASIONAL
  description: Posterior-column and sensory-nerve involvement can impair proprioception.
  phenotype_term:
    preferred_term: Impaired proprioception
    term:
      id: HP:0010831
      label: Impaired proprioception
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0010831 | Impaired proprioception | Occasional (29-5%)"
    explanation: Orphanet records impaired proprioception as an occasional phenotype.
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "deep tendon reflexes, vibratory sense, and proprioception; muscle weakness;"
    explanation: GeneReviews describes progressive loss of proprioception in untreated individuals.
- name: Peripheral neuropathy
  category: Neurologic
  description: Progressive peripheral neuropathy is a hallmark later neuromuscular complication.
  phenotype_term:
    preferred_term: Peripheral neuropathy
    term:
      id: HP:0009830
      label: Peripheral neuropathy
  evidence:
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.)"
    explanation: The contemporary review lists peripheral neuropathy among later neuromuscular manifestations.
- name: Myopathy
  category: Musculoskeletal
  frequency: OCCASIONAL
  description: Myopathy can accompany the progressive neuromuscular phenotype.
  phenotype_term:
    preferred_term: Myopathy
    term:
      id: HP:0003198
      label: Myopathy
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003198 | Myopathy | Occasional (29-5%)"
    explanation: Orphanet records myopathy as an occasional phenotype.
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.)"
    explanation: The contemporary review lists myopathy among later neuromuscular manifestations.
- name: Muscle weakness
  category: Neurologic
  description: Progressive neuropathy or myopathy can manifest as muscle weakness.
  phenotype_term:
    preferred_term: Muscle weakness
    term:
      id: HP:0001324
      label: Muscle weakness
  evidence:
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "deep tendon reflexes, vibratory sense, and proprioception; muscle weakness;"
    explanation: GeneReviews includes muscle weakness among untreated neuromuscular findings.
- name: Pes cavus
  category: Musculoskeletal
  frequency: OCCASIONAL
  description: Cavus foot morphology can accompany neuromuscular involvement.
  phenotype_term:
    preferred_term: Pes cavus
    term:
      id: HP:0001761
      label: Pes cavus
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001761 | Pes cavus | Occasional (29-5%)"
    explanation: Orphanet records pes cavus as an occasional phenotype.
- name: Progressive visual loss
  category: Ophthalmologic
  frequency: FREQUENT
  description: Progressive retinal involvement can impair vision.
  phenotype_term:
    preferred_term: Progressive visual loss
    term:
      id: HP:0000529
      label: Progressive visual loss
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000529 | Progressive visual loss | Frequent (79-30%)"
    explanation: Orphanet records progressive visual loss as frequent.
- name: Rod-cone dystrophy
  category: Ophthalmologic
  frequency: OCCASIONAL
  description: Retinal degeneration can present as rod-cone dystrophy.
  phenotype_term:
    preferred_term: Rod-cone dystrophy
    term:
      id: HP:0000510
      label: Rod-cone dystrophy
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000510 | Rod-cone dystrophy | Occasional (29-5%)"
    explanation: Orphanet records rod-cone dystrophy as an occasional phenotype.
- name: Color vision defect
  category: Ophthalmologic
  frequency: FREQUENT
  description: Retinal disease can affect color vision.
  phenotype_term:
    preferred_term: Color vision defect
    term:
      id: HP:0000551
      label: Color vision defect
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000551 | Color vision defect | Frequent (79-30%)"
    explanation: Orphanet records color vision defect as frequent.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "with progressive loss of night vision and/or color vision in adulthood."
    explanation: GeneReviews supports acquired loss of color vision as a retinal manifestation.
- name: Nyctalopia
  category: Ophthalmologic
  frequency: FREQUENT
  description: Night blindness can occur with retinal involvement.
  phenotype_term:
    preferred_term: Nyctalopia
    term:
      id: HP:0000662
      label: Nyctalopia
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000662 | Nyctalopia | Frequent (79-30%)"
    explanation: Orphanet records nyctalopia as frequent.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "with progressive loss of night vision and/or color vision in adulthood."
    explanation: GeneReviews supports night vision loss as a retinal manifestation.
- name: Abnormal retinal pigmentation
  category: Ophthalmologic
  frequency: FREQUENT
  description: Retinal pigmentation abnormalities develop in untreated retinal disease.
  phenotype_term:
    preferred_term: Abnormal retinal pigmentation
    term:
      id: HP:0007703
      label: Abnormal retinal pigmentation
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0007703 | Abnormality of retinal pigmentation | Frequent (79-30%)"
    explanation: Orphanet records abnormal retinal pigmentation as frequent.
- name: Prolonged prothrombin time
  category: Hematologic
  frequency: OCCASIONAL
  description: Vitamin K malabsorption can increase INR or prolong prothrombin time.
  phenotype_term:
    preferred_term: Prolonged prothrombin time
    term:
      id: HP:0008151
      label: Prolonged prothrombin time
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0008151 | Prolonged prothrombin time | Occasional (29-5%)"
    explanation: Orphanet records prolonged prothrombin time as occasional.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "result in an increased international normalized ratio (INR)."
    explanation: GeneReviews links fat-soluble vitamin malabsorption to increased INR.
- name: Abnormal bleeding
  category: Hematologic
  frequency: VERY_RARE
  description: Abnormal bleeding can occur as a rare coagulation manifestation.
  phenotype_term:
    preferred_term: Abnormal bleeding
    term:
      id: HP:0001892
      label: Abnormal bleeding
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001892 | Abnormal bleeding | Very rare (<4-1%)"
    explanation: Orphanet records abnormal bleeding as a very rare phenotype.
- name: Hepatomegaly
  category: Hepatic
  frequency: OCCASIONAL
  description: Liver enlargement can occur.
  phenotype_term:
    preferred_term: Hepatomegaly
    term:
      id: HP:0002240
      label: Hepatomegaly
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002240 | Hepatomegaly | Occasional (29-5%)"
    explanation: Orphanet records hepatomegaly as occasional.
- name: Hepatic steatosis
  category: Hepatic
  frequency: OCCASIONAL
  description: Hepatic steatosis is a recognized hepatic manifestation.
  phenotype_term:
    preferred_term: Hepatic steatosis
    term:
      id: HP:0001397
      label: Hepatic steatosis
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001397 | Hepatic steatosis | Occasional (29-5%)"
    explanation: Orphanet records hepatic steatosis as occasional.
- name: Elevated circulating hepatic transaminase concentration
  category: Hepatic
  frequency: OCCASIONAL
  description: Hepatic involvement can include elevated circulating transaminases.
  phenotype_term:
    preferred_term: Elevated circulating hepatic transaminase concentration
    term:
      id: HP:0002910
      label: Elevated circulating hepatic transaminase concentration
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002910 | Elevated circulating hepatic transaminase concentration | Occasional (29-5%)"
    explanation: Orphanet records elevated circulating hepatic transaminases as an occasional phenotype.
  reports_on:
  - target: Hepatic Triglyceride Retention
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Hepatic involvement can include elevated serum transaminases.
    evidence:
    - reference: ORPHA:14
      reference_title: "Abetalipoproteinemia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0002910 | Elevated circulating hepatic transaminase concentration | Occasional (29-5%)"
      explanation: Orphanet records elevated hepatic transaminases as an occasional hepatic phenotype of ABL.
- name: Hepatic fibrosis
  category: Hepatic
  frequency: VERY_RARE
  description: Hepatic fibrosis is recorded as a very rare hepatic complication.
  phenotype_term:
    preferred_term: Hepatic fibrosis
    term:
      id: HP:0001395
      label: Hepatic fibrosis
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001395 | Hepatic fibrosis | Very rare (<4-1%)"
    explanation: Orphanet records hepatic fibrosis as a very rare phenotype.
- name: Cirrhosis
  category: Hepatic
  frequency: VERY_RARE
  description: Advanced liver disease can rarely progress to cirrhosis.
  phenotype_term:
    preferred_term: Cirrhosis
    term:
      id: HP:0001394
      label: Cirrhosis
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001394 | Cirrhosis | Very rare (<4-1%)"
    explanation: Orphanet records cirrhosis as a very rare phenotype.
  - reference: PMID:32039990
    reference_title: "Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Fatty liver, cirrhosis and hepatocellular carcinoma have been reported in FHBL and ABL"
    explanation: The liver review reports cirrhosis among documented ABL liver outcomes.
biochemical:
- name: Absent apoB-containing lipoproteins
  presence: DECREASED
  context: >-
    ApoB-containing lipoproteins, including chylomicrons, VLDL, and LDL, are
    absent or virtually absent in plasma.
  evidence:
  - reference: PMID:24288038
    reference_title: "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "virtually absent apo B-containing lipoproteins, including chylomicrons, very low density lipoprotein and low density lipoprotein."
    explanation: The review directly supports the defining plasma lipoprotein abnormality.
- name: Low fat-soluble vitamin concentrations
  presence: DECREASED
  context: >-
    Circulating vitamins A, D, and E are monitored because intestinal
    fat-soluble-vitamin absorption and transport are impaired; vitamin K
    deficiency is often assessed through coagulation measures.
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0004905 | Low levels of vitamin A | Frequent (79-30%)"
    explanation: Orphanet directly records low vitamin A concentrations.
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0100512 | Low levels of vitamin D | Frequent (79-30%)"
    explanation: Orphanet directly records low vitamin D concentrations.
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0100513 | Low levels of vitamin E | Very frequent (99-80%)"
    explanation: Orphanet directly records low vitamin E concentrations.
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "fat-soluble vitamin levels"
    explanation: GeneReviews identifies the circulating vitamin measures used in longitudinal assessment.
genetic:
- name: MTTP pathogenic variants
  gene_term:
    preferred_term: MTTP
    term:
      id: hgnc:7467
      label: MTTP
  association: Causative biallelic pathogenic variants
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE
  inheritance:
  - name: Autosomal recessive inheritance
    inheritance_term:
      preferred_term: Autosomal recessive inheritance
      term:
        id: HP:0000007
        label: Autosomal recessive inheritance
    evidence:
    - reference: PMID:30358967
      reference_title: "Abetalipoproteinemia."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Abetalipoproteinemia is inherited in an autosomal recessive"
      explanation: GeneReviews states the autosomal recessive inheritance pattern.
  variants:
  - name: Biallelic MTTP pathogenic variants
    description: >
      Reported disease-causing MTTP variants include frameshift, splice-site,
      and missense variants; functional studies show that selected missense
      variants can impair MTP lipid-transfer activity or formation of the active
      MTP complex.
    gene:
      preferred_term: MTTP
      term:
        id: hgnc:7467
        label: MTTP
    clinical_significance: PATHOGENIC
    type: loss_of_function_variant
    functional_effects:
    - function: MTP lipid transfer activity
      description: Pathogenic variants reduce functional MTP activity or disrupt active MTP complex formation.
      type: loss-of-function
    evidence:
    - reference: PMID:30358967
      reference_title: "Abetalipoproteinemia."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "biallelic pathogenic variants in MTTP"
      explanation: GeneReviews identifies biallelic MTTP pathogenic variants as the molecular diagnostic cause.
    - reference: PMID:10946006
      reference_title: "Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Three novel mutations have been identified: a frameshift mutation caused
        by a single adenine deletion at position 1389 of the cDNA, and a missense
        mutation, Asn780Tyr, each in homozygous forms; and a splice site mutation,
        2218-2A-->G, in a compound heterozygous form.
      explanation: Patient variant screening identified frameshift, missense, and splice-site MTTP mutations in ABL.
    - reference: PMID:8939939
      reference_title: "A novel abetalipoproteinemia genotype. Identification of a missense mutation in the 97-kDa subunit of the microsomal triglyceride transfer protein that prevents complex formation with protein disulfide isomerase."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "Biochemical analysis of lysates from these cells showed that the Arg to His conversion interrupted the interaction between the 97-kDa subunit and protein disulfide isomerase."
      explanation: Functional evidence shows one MTTP missense variant disrupts formation of the MTP complex.
  evidence:
  - reference: ORPHA:14
    reference_title: Abetalipoproteinemia
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MTTP | microsomal triglyceride transfer protein | hgnc:7467 | Disease-causing germline mutation(s) in"
    explanation: Orphanet records MTTP as a disease-causing germline gene for Abetalipoproteinemia.
  - reference: PMID:30358967
    reference_title: "Abetalipoproteinemia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "biallelic pathogenic variants in MTTP"
    explanation: GeneReviews supports biallelic MTTP pathogenic variants as diagnostic for Abetalipoproteinemia.
treatments:
- name: Calorie-adequate low-fat diet
  therapeutic_modality: BEHAVIORAL
  description: >-
    Management guidance recommends adequate calories for growth together with a
    low-fat diet, generally limiting long-chain fat that cannot be transported
    normally in chylomicrons. This reduces gastrointestinal fat load but does
    not correct the MTTP defect.
  action_category: THERAPEUTIC
  treatment_term:
    preferred_term: dietary intervention
    term:
      id: NCIT:C15447
      label: Dietary Intervention
  target_mechanisms:
  - target: Impaired Intestinal Lipid Absorption
    treatment_effect: MODULATES
    description: Reducing dietary long-chain fat limits the substrate burden on the impaired intestinal transport pathway.
    evidence:
    - reference: PMID:30358967
      reference_title: Abetalipoproteinemia.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "low-fat diet (10%-20% of total calories from fat)"
      explanation: GeneReviews provides the low-fat dietary management framework.
  evidence:
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Adequate caloric intake to alleviate growth deficiency; low-fat diet (10%-20% of total calories from fat)"
    explanation: GeneReviews recommends adequate calories and a low-fat diet for growth and gastrointestinal management.
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Fatty foods, particularly those rich in long-chain fatty acids."
    explanation: GeneReviews identifies long-chain-fat-rich foods as the principal dietary exposure to avoid.
- name: High-dose fat-soluble vitamin supplementation
  description: >-
    Long-term vitamins A, D, E, and K replace nutrients that remain poorly
    absorbed. Observational evidence suggests early replacement may prevent or
    delay retinal and neuromuscular progression, but established dysfunction is
    not reliably reversed. Dosing requires specialist biochemical monitoring;
    vitamin A needs pregnancy-specific adjustment because excess can harm the
    developing fetus.
  action_category: THERAPEUTIC
  treatment_term:
    preferred_term: nutritional supplementation
    term:
      id: NCIT:C15433
      label: Nutritional Support
  target_mechanisms:
  - target: Reduced Fat-Soluble Vitamin Bioavailability
    treatment_effect: MODULATES
    description: High-dose replacement increases vitamin availability despite persistent intestinal malabsorption without restoring normal chylomicron transport.
    evidence:
    - reference: PMID:33994405
      reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications"
      explanation: The review supports replacement as the treatment mainstay while using appropriately qualified benefit language.
  - target: Vitamin A/E-Associated Retinal Degeneration
    treatment_effect: MODULATES
    description: Vitamin A and E replacement may slow retinal deterioration, particularly when started early.
    evidence:
    - reference: PMID:7171526
      reference_title: Combined vitamin A and E therapy prevents retinal electrophysiological deterioration in abetalipoproteinaemia.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "After initiation of vitamin A and E therapy no progression of disturbed visual function could be detected in any patient."
      explanation: An eight-patient follow-up observed stable retinal function after combined vitamin therapy.
  - target: Vitamin E-Associated Neuromuscular Injury
    treatment_effect: MODULATES
    description: High-dose vitamin E may slow or arrest progressive neuropathy and myopathy, but the evidence is observational.
    evidence:
    - reference: PMID:2981135
      reference_title: Arrest of neuropathy and myopathy in abetalipoproteinemia with high-dose vitamin E therapy.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "It was concluded that treatment with high doses of vitamin E was responsible for the arrest of the usually progressive neuropathy and myopathy."
      explanation: A long-term single-patient observation supports possible arrest of progressive neuromuscular disease.
  evidence:
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "However, it cannot fully prevent or restore impaired function."
    explanation: The review cautions that vitamin replacement is not fully preventive or restorative.
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Vitamin A excess can be harmful to the developing fetus."
    explanation: GeneReviews supports pregnancy-specific caution with high-dose vitamin A.
- name: Essential fatty acid supplementation
  description: >-
    Small amounts of oils rich in polyunsaturated fatty acids can be used as
    tolerated to provide essential fatty acids despite overall dietary fat
    restriction.
  action_category: THERAPEUTIC
  treatment_term:
    preferred_term: nutritional supplementation
    term:
      id: NCIT:C15433
      label: Nutritional Support
  evidence:
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "essential fatty acid supplementation (up to 1 teaspoon per day of oils rich in polyunsaturated fatty acids, as tolerated)"
    explanation: GeneReviews recommends essential-fatty-acid supplementation as tolerated.
  - reference: PMID:24288038
    reference_title: "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "supplementation with essential fatty acids and high oral doses of fat soluble vitamins."
    explanation: The management review lists essential fatty acids among treatment mainstays.
- name: Multisystem surveillance
  description: >-
    Longitudinal follow-up assesses growth, blood count and reticulocytes,
    coagulation, liver tests and imaging, fat-soluble vitamins and related
    chemistries, lipids, and neurologic and ophthalmologic status. The intervals
    in GeneReviews provide a general evidence source rather than individualized
    medical instructions.
  action_category: MONITORING
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Complete blood count, INR, reticulocyte count, liver function tests (AST,
      ALT, GGT, total and direct bilirubin, alkaline phosphatase, and albumin),
      fat-soluble vitamin levels
    explanation: GeneReviews specifies annual hematologic, coagulation, hepatic, and vitamin monitoring.
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Ultrasound of the liver every three years. Ophthalmology and neurology evaluations every six to 12 months."
    explanation: GeneReviews specifies periodic liver imaging and specialist neurologic and ophthalmologic review.
- name: Genetic counseling and family evaluation
  description: >-
    Counseling addresses autosomal-recessive recurrence risk, carrier testing,
    evaluation of at-risk siblings, and reproductive options when familial MTTP
    variants are known.
  action_category: COUNSELING_INFORMATIONAL
  treatment_term:
    preferred_term: Genetic Counseling
    term:
      id: NCIT:C15240
      label: Genetic Counseling
  evidence:
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier"
    explanation: GeneReviews provides the autosomal-recessive recurrence-risk framework.
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible if the pathogenic MTTP variants in the family are known."
    explanation: GeneReviews supports carrier and reproductive testing after familial-variant identification.
diagnosis:
- name: Plasma lipid and apoB measurement
  diagnosis_term:
    preferred_term: blood chemistry measurement
    term:
      id: NCIT:C47868
      label: Blood Chemistry Measurement
  description: >-
    Absent or extremely low LDL cholesterol, triglyceride, and apoB is the
    defining biochemical pattern and should prompt molecular testing. LDL-C and
    apoB below 15 mg/dL have been proposed as Japanese screening or
    eligibility thresholds, not as universal stand-alone diagnostic criteria.
  results: Absent or extremely low LDL cholesterol, triglyceride, and apoB strongly supports the diagnosis but does not distinguish MTTP-related ABL from all genetic mimics.
  evidence:
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "absent or extremely low LDL-cholesterol, triglyceride, and apolipoprotein (apo) B levels"
    explanation: GeneReviews defines the characteristic biochemical diagnostic pattern.
  - reference: PMID:33994405
    reference_title: Current Diagnosis and Management of Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) ＜15 mg/dL and apoB ＜15 mg/dL can be useful in universal or opportunistic screening"
    explanation: The review frames the numerical thresholds as screening or program-entry criteria rather than a universal molecular diagnosis.
- name: Peripheral blood smear morphology
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: NCIT:C124351
      label: Clinical Evaluation
  description: >-
    A peripheral blood smear can demonstrate acanthocytosis, a strong
    supportive clue in the appropriate severe-hypolipidemia and malabsorption
    phenotype.
  results: Acanthocytosis supports the clinical diagnosis but is not a substitute for molecular confirmation.
  evidence:
  - reference: PMID:24288038
    reference_title: "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Clinical diagnosis is based on signs and symptoms, acanthocytosis on blood smear, and virtually absent apo B-containing lipoproteins"
    explanation: The review identifies acanthocytosis on smear as part of clinical diagnosis.
- name: MTTP molecular genetic testing
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: NCIT:C19770
      label: Molecular Analysis
    qualifiers:
    - predicate:
        preferred_term: has participant
        term:
          id: RO:0000057
          label: has participant
      value:
        preferred_term: MTTP
        term:
          id: hgnc:7467
          label: MTTP
  description: >-
    Identification of biallelic pathogenic or likely pathogenic MTTP variants
    confirms MTTP-related abetalipoproteinemia in a patient with the compatible
    biochemical and clinical phenotype.
  results: Biallelic pathogenic or likely pathogenic MTTP variants establish the molecular diagnosis.
  evidence:
  - reference: PMID:30358967
    reference_title: Abetalipoproteinemia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "biallelic pathogenic variants in MTTP identified by molecular genetic testing."
    explanation: GeneReviews identifies biallelic MTTP variants found by molecular testing as the confirmatory criterion.
references:
- reference: ORPHA:14
  title: Abetalipoproteinemia
- reference: PMID:10946006
  title: Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia.
- reference: PMID:1439810
  title: Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia.
- reference: PMID:24288038
  title: "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management."
- reference: PMID:24842304
  title: Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia.
- reference: PMID:26086616
  title: Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia.
- reference: PMID:2981135
  title: Arrest of neuropathy and myopathy in abetalipoproteinemia with high-dose vitamin E therapy.
- reference: PMID:30358967
  title: Abetalipoproteinemia.
  tags:
  - GeneReviews
- reference: PMID:30640893
  title: "Chylomicron retention disease: genetics, biochemistry, and clinical spectrum."
- reference: PMID:32039990
  title: "Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease."
- reference: PMID:33994405
  title: Current Diagnosis and Management of Abetalipoproteinemia.
- reference: PMID:36243606
  title: Guidance for the diagnosis and treatment of hypolipidemia disorders.
- reference: PMID:7171526
  title: Combined vitamin A and E therapy prevents retinal electrophysiological deterioration in abetalipoproteinaemia.
- reference: PMID:7782284
  title: A 30-amino acid truncation of the microsomal triglyceride transfer protein large subunit disrupts its interaction with protein disulfide-isomerase and causes abetalipoproteinemia.
- reference: PMID:8939939
  title: A novel abetalipoproteinemia genotype. Identification of a missense mutation in the 97-kDa subunit of the microsomal triglyceride transfer protein that prevents complex formation with protein disulfide isomerase.
differential_diagnoses:
- name: Familial hypobetalipoproteinemia 1
  description: >-
    Severe biallelic APOB-related familial hypobetalipoproteinemia can be
    clinically and biochemically very similar to abetalipoproteinemia, but it is
    caused by APOB rather than MTTP variants.
  disease_term:
    preferred_term: familial hypobetalipoproteinemia 1
    term:
      id: MONDO:0014252
      label: familial hypobetalipoproteinemia 1
  distinguishing_features:
  - Biallelic pathogenic MTTP variants establish abetalipoproteinemia; biallelic APOB variants establish severe familial hypobetalipoproteinemia.
  - Obligate heterozygous parents usually have normal lipid levels in MTTP-related ABL but approximately half-normal apoB-containing lipoproteins in severe APOB-related disease.
  evidence:
  - reference: PMID:24288038
    reference_title: "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "mutations either in both alleles of the MTP (alias MTTP) gene encoding microsomal triglyceride transfer protein (MTP) or both alleles of the APOB gene itself in the case of ABL and HHBL, respectively."
    explanation: The review distinguishes the two phenocopies by their causal genes.
  - reference: PMID:24288038
    reference_title: "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Obligate heterozygote parents of ABL patients usually have normal lipids"
    explanation: The review supplies a useful family-lipid discriminator.
  - reference: PMID:36243606
    reference_title: Guidance for the diagnosis and treatment of hypolipidemia disorders.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease"
    explanation: Contemporary guidance treats these as related but distinct monogenic hypolipidemia disorders.
- name: Chylomicron retention disease
  description: >-
    SAR1B-related chylomicron retention disease also causes early fat
    malabsorption, hypocholesterolemia, and fat-soluble-vitamin deficiency, but
    the defect is ER-to-Golgi transport of chylomicron cargo rather than
    MTTP-dependent apoB-particle lipidation and assembly.
  disease_term:
    preferred_term: chylomicron retention disease
    term:
      id: MONDO:0009528
      label: chylomicron retention disease
  distinguishing_features:
  - Biallelic MTTP variants favor abetalipoproteinemia, whereas biallelic SAR1B variants favor chylomicron retention disease.
  - Postprandial absence of chylomicrons and apoB48 with a SAR1B/COPII transport defect supports chylomicron retention disease.
  evidence:
  - reference: PMID:30640893
    reference_title: "Chylomicron retention disease: genetics, biochemistry, and clinical spectrum."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "CRD patients present with SAR1B mutations, which disable the formation of coat protein complex II and thus blocks the transport of chylomicron cargo from the endoplasmic reticulum to the Golgi."
    explanation: The review identifies the distinct SAR1B/COPII transport mechanism.
  - reference: PMID:30640893
    reference_title: "Chylomicron retention disease: genetics, biochemistry, and clinical spectrum."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Molecular testing for CRD is recommended to distinguish the disease from other congenital fat malabsorptions"
    explanation: The review explicitly recommends molecular testing to distinguish this phenocopy.
review_notes: >-
  Re-reviewed in July 2026 as MTTP-specific abetalipoproteinemia. The revision
  removed the historical APOB disease conflation and disease-external analogies,
  rebuilt the causal graph around apoB-particle assembly and secretion, added
  treatment-modified natural history, monitoring, diagnostic separation, and
  structured differentials, and aligned every retained evidence title with its
  cache. Remaining mechanistic gaps include the detailed erythrocyte-membrane
  pathway to acanthocytosis, reliable genotype-phenotype correlations, and
  long-term natural-history data under modern treatment.
clinical_trials: []
datasets: []
📚

References & Deep Research

References

15
ORPHA:14
Abetalipoproteinemia
No top-level findings curated for this source.
PMID:10946006
Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia.
No top-level findings curated for this source.
PMID:1439810
Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia.
No top-level findings curated for this source.
PMID:24288038
Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management.
No top-level findings curated for this source.
PMID:24842304
Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia.
No top-level findings curated for this source.
PMID:26086616
Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia.
No top-level findings curated for this source.
PMID:2981135
Arrest of neuropathy and myopathy in abetalipoproteinemia with high-dose vitamin E therapy.
No top-level findings curated for this source.
PMID:30358967
Abetalipoproteinemia.
No top-level findings curated for this source.
PMID:30640893
Chylomicron retention disease: genetics, biochemistry, and clinical spectrum.
No top-level findings curated for this source.
PMID:32039990
Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease.
No top-level findings curated for this source.
PMID:33994405
Current Diagnosis and Management of Abetalipoproteinemia.
No top-level findings curated for this source.
PMID:36243606
Guidance for the diagnosis and treatment of hypolipidemia disorders.
No top-level findings curated for this source.
PMID:7171526
Combined vitamin A and E therapy prevents retinal electrophysiological deterioration in abetalipoproteinaemia.
No top-level findings curated for this source.
PMID:7782284
A 30-amino acid truncation of the microsomal triglyceride transfer protein large subunit disrupts its interaction with protein disulfide-isomerase and causes abetalipoproteinemia.
No top-level findings curated for this source.
PMID:8939939
A novel abetalipoproteinemia genotype. Identification of a missense mutation in the 97-kDa subunit of the microsomal triglyceride transfer protein that prevents complex formation with protein disulfide isomerase.
No top-level findings curated for this source.

Deep Research

1
Abetalipoproteinemia Deep Research Fallback ▸

Abetalipoproteinemia Deep Research Fallback

Provider Attempts

  • 2026-05-04T05:24Z: timeout 120 just research-disorder falcon Abetalipoproteinemia timed out with exit code 124 after the provider command was terminated by timeout.
  • 2026-05-04T05:26Z: timeout 120 just research-disorder openai Abetalipoproteinemia timed out with exit code 124 after the provider command was terminated by timeout.

No provider-generated research artifact was available to integrate. Curation therefore proceeded from generated structured Orphanet evidence and fetched PubMed caches, without hand-editing any references_cache/*.md files.

Evidence Scope Used For Curation

  • ORPHA:14 structured record for disease definition, MONDO exact mapping, inheritance, prevalence, MTTP gene association, onset, and HPO phenotype frequencies.
  • PMID:24288038 for the canonical management framework and the mechanism that defective packaging and secretion of apoB-containing lipoproteins underlies abetalipoproteinemia.
  • PMID:30358967 for GeneReviews clinical characteristics, diagnosis/testing, diet and vitamin management, surveillance, and genetic counseling.
  • PMID:10946006 for patient MTTP variant screening and functional evidence that MTP gene defects are the proximal cause of abetalipoproteinemia.
  • PMID:8939939 for functional evidence that an abetalipoproteinemia-associated MTTP missense variant disrupts formation of an active MTP complex with protein disulfide isomerase.
  • PMID:30522860 for clinical evidence that deleterious MTTP variants produce undetectable apoB, extremely low LDL cholesterol, and inability to export apoB-containing lipoproteins from intestine and liver.
  • PMID:18611256 for long-term human clinical reports supporting high-dose fat-soluble vitamin treatment, including vitamin E, with arrest of neuropathy and other complications.

Curation Conclusions

The accepted disease model is MTTP loss of function causing defective intestinal chylomicron assembly and hepatic VLDL assembly, with loss of apoB-containing lipoprotein secretion. This explains the biochemical profile of absent or extremely low apoB lipoproteins, hypocholesterolemia, hypotriglyceridemia, fat malabsorption, and secondary fat-soluble vitamin deficiency. The clinical graph links these defects to ORPHA-supported gastrointestinal, hematologic, retinal, neurologic, hepatic, and biochemical phenotypes. Treatment evidence supports low-fat diet, essential fatty acid supplementation, and high-dose fat-soluble vitamin supplementation as the main management axis.