Niemann-Pick disease type A (NPD-A) is the severe, infantile-onset neuronopathic end of the acid sphingomyelinase deficiency (ASMD) spectrum, caused by biallelic loss-of-function variants in SMPD1 encoding acid sphingomyelinase. Profound enzyme deficiency leads to lysosomal accumulation of sphingomyelin (with secondary cholesterol) in macrophages and neurons, producing early hepatosplenomegaly, failure to thrive, a macular cherry-red spot, and rapidly progressive neurodegeneration, with death typically by 2-3 years of age. Enzyme replacement therapy (olipudase alfa) addresses visceral disease in ASMD but does not cross the blood-brain barrier, so management of NPD-A remains supportive.
Ask a research question about Niemann-Pick Disease Type A. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
Conditions with similar clinical presentations that must be differentiated from Niemann-Pick Disease Type A:
name: Niemann-Pick Disease Type A
creation_date: "2026-06-13T00:00:00Z"
description: >-
Niemann-Pick disease type A (NPD-A) is the severe, infantile-onset neuronopathic end
of the acid sphingomyelinase deficiency (ASMD) spectrum, caused by biallelic
loss-of-function variants in SMPD1 encoding acid sphingomyelinase. Profound enzyme
deficiency leads to lysosomal accumulation of sphingomyelin (with secondary
cholesterol) in macrophages and neurons, producing early hepatosplenomegaly, failure
to thrive, a macular cherry-red spot, and rapidly progressive neurodegeneration, with
death typically by 2-3 years of age. Enzyme replacement therapy (olipudase alfa)
addresses visceral disease in ASMD but does not cross the blood-brain barrier, so
management of NPD-A remains supportive.
category: Mendelian
disease_term:
preferred_term: Niemann-Pick disease type A
term:
id: MONDO:0009756
label: Niemann-Pick disease type A
mappings:
mondo_mappings:
- term:
id: MONDO:0009756
label: Niemann-Pick disease type A
mapping_predicate: skos:exactMatch
mapping_source: MONDO
mapping_justification: Primary MONDO disease identifier for this Niemann-Pick disease type A entry.
synonyms:
- Acid sphingomyelinase deficiency type A
- Infantile neurovisceral ASMD
- ASMD type A
- Niemann-Pick disease, type A
parents:
- sphingolipidosis
pathophysiology:
- name: SMPD1 Loss of Function and Acid Sphingomyelinase Deficiency
conforms_to: "lysosomal_substrate_accumulation#Lysosomal Hydrolase or Cofactor Deficiency"
description: >-
Biallelic loss-of-function variants in SMPD1 (sphingomyelin phosphodiesterase 1)
abolish lysosomal acid sphingomyelinase activity. The enzyme normally hydrolyzes
sphingomyelin to ceramide and phosphocholine; its near-complete loss is the primary
biochemical lesion of NPD-A.
gene:
preferred_term: SMPD1
term:
id: hgnc:11120
label: SMPD1
biological_processes:
- preferred_term: sphingomyelin catabolic process
modifier: DECREASED
term:
id: GO:0006685
label: sphingomyelin catabolic process
evidence:
- reference: PMID:28164782
reference_title: "Types A and B Niemann-Pick disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "All patients with types A and B NPD have mutations in the gene encoding ASM (SMPD1), and thus the disease is more accurately referred to as ASM deficiency (ASMD)."
explanation: "Establishes SMPD1 mutation and acid sphingomyelinase deficiency as the cause of NPD type A."
- reference: PMID:38397448
reference_title: "The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann-Pick Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "NPD type A and B are caused by mutations in the gene SMPD1 coding for sphingomyelin phosphodiesterase 1, with a consequent lack of acid sphingomyelinase activity."
explanation: "Confirms the SMPD1/acid sphingomyelinase mechanism."
downstream:
- target: Lysosomal Sphingomyelin and Secondary Lipid Accumulation
description: Loss of enzyme activity allows undegraded sphingomyelin to accumulate in lysosomes.
- name: Lysosomal Sphingomyelin and Secondary Lipid Accumulation
conforms_to: "lysosomal_substrate_accumulation#Lysosomal Substrate Accumulation"
description: >-
Undegraded sphingomyelin, together with secondary cholesterol, accumulates in the
lysosomes of macrophages and neurons, producing lipid-laden foam cells throughout the
reticuloendothelial system and the nervous system.
cell_types:
- preferred_term: macrophage
term:
id: CL:0000235
label: macrophage
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
cellular_components:
- preferred_term: lysosome
term:
id: GO:0005764
label: lysosome
biological_processes:
- preferred_term: sphingomyelin metabolic process
modifier: ABNORMAL
term:
id: GO:0006684
label: sphingomyelin metabolic process
evidence:
- reference: PMID:28164782
reference_title: "Types A and B Niemann-Pick disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "varying degrees of lipid storage and foam cell infiltration in tissues"
explanation: "Sphingomyelin storage produces foam-cell (lipid-laden macrophage) infiltration of tissues."
downstream:
- target: Visceral and Neuronal Storage Pathology
description: Foam-cell and neuronal storage drives organomegaly and neurodegeneration.
- name: Visceral and Neuronal Storage Pathology
description: >-
Storage pathology produces early hepatosplenomegaly from reticuloendothelial foam
cells and, in the neuronopathic type A, profound CNS involvement with rapidly
progressive psychomotor degeneration leading to early childhood death.
cell_types:
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
locations:
- preferred_term: spleen
term:
id: UBERON:0002106
label: spleen
- preferred_term: liver
term:
id: UBERON:0002107
label: liver
evidence:
- reference: PMID:28164782
reference_title: "Types A and B Niemann-Pick disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Type A NPD patients exhibit hepatosplenomegaly in infancy and profound CNS involvement."
explanation: "Type A storage pathology produces infantile hepatosplenomegaly with profound CNS involvement."
downstream:
- target: Hepatosplenomegaly
description: Reticuloendothelial foam-cell accumulation enlarges liver and spleen.
- target: Neurodegeneration
description: Neuronal sphingomyelin storage drives progressive neurodegeneration.
- target: Failure to thrive
description: Infantile visceral and neurologic disease impairs growth and feeding.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- target: Hypotonia
description: Neuronal storage pathology contributes to profound infantile hypotonia.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- target: Developmental regression
description: Progressive neuronal storage pathology causes loss of developmental progress.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- target: Cherry red spot of the macula
description: Retinal ganglion-cell lipid storage produces the macular cherry-red spot.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
phenotypes:
- name: Hepatosplenomegaly
description: Early enlargement of liver and spleen from sphingomyelin-laden foam cells, often by 2-4 months of age.
phenotype_term:
preferred_term: Hepatosplenomegaly
term:
id: HP:0001433
label: Hepatosplenomegaly
evidence:
- reference: PMID:28164782
reference_title: "Types A and B Niemann-Pick disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Type A NPD patients exhibit hepatosplenomegaly in infancy and profound CNS involvement."
explanation: "Hepatosplenomegaly in infancy is a hallmark of type A."
- name: Failure to thrive
description: Failure to thrive begins in infancy as feeding and systemic disease worsen.
phenotype_term:
preferred_term: Failure to thrive
term:
id: HP:0001508
label: Failure to thrive
evidence:
- reference: PMID:28164782
reference_title: "Types A and B Niemann-Pick disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Type A NPD patients exhibit hepatosplenomegaly and failure to thrive within the first year of life."
explanation: "Failure to thrive is an early infantile manifestation of NPD-A."
- name: Neurodegeneration
description: Rapidly progressive psychomotor degeneration in infancy.
phenotype_term:
preferred_term: Neurodegeneration
term:
id: HP:0002180
label: Neurodegeneration
evidence:
- reference: PMID:28228103
reference_title: "Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "NPD A is associated with a uniformly devastating disease course, with rapidly progressing psychomotor degeneration"
explanation: "Rapidly progressive psychomotor (neuro)degeneration defines the type A course."
- name: Hypotonia
description: Profound hypotonia is part of the rapidly progressive neurologic decline.
phenotype_term:
preferred_term: Hypotonia
term:
id: HP:0001252
label: Hypotonia
evidence:
- reference: PMID:28164782
reference_title: "Types A and B Niemann-Pick disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "profound hypotonia and failure to attain milestones"
explanation: "Profound hypotonia is reported as part of the type A neurodegenerative course."
- name: Developmental regression
description: Loss of acquired developmental milestones beginning in the first year of life.
phenotype_term:
preferred_term: Developmental regression
term:
id: HP:0002376
label: Developmental regression
evidence:
- reference: PMID:28228103
reference_title: "Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "rapidly progressing psychomotor degeneration"
explanation: "Psychomotor degeneration manifests as regression of acquired milestones."
- name: Cherry red spot of the macula
description: >-
A macular cherry-red spot from perifoveal ganglion-cell lipid storage is a
characteristic ophthalmologic sign of NPD-A.
phenotype_term:
preferred_term: Cherry red spot of the macula
term:
id: HP:0010729
label: Cherry red spot of the macula
evidence:
- reference: PMID:28164782
reference_title: "Types A and B Niemann-Pick disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "cherry-red spot is present in the macula in ~50% of these infants"
explanation: "A macular cherry-red spot is present in about half of NPD-A infants."
inheritance:
- name: Autosomal recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:37069638
reference_title: "Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann-Pick disease types A, B and A/B)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Acid Sphingomyelinase Deficiency (ASMD) is a rare autosomal recessive disorder caused by mutations in the SMPD1 gene."
explanation: "ASMD/NPD-A is inherited in an autosomal recessive manner."
genetic:
- name: SMPD1
association: Biallelic loss-of-function SMPD1 variants causing acid sphingomyelinase deficiency
relationship_type: CAUSATIVE
variant_origin: GERMLINE
gene_term:
preferred_term: SMPD1
term:
id: hgnc:11120
label: SMPD1
evidence:
- reference: PMID:28228103
reference_title: "Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, is an autosomal recessive genetic disorder caused by different SMPD1 mutations."
explanation: "SMPD1 mutations are the genetic cause of ASMD/NPD-A."
progression:
- phase: Fatal infantile course
notes: >-
NPD-A follows a uniformly devastating, rapidly progressive neurodegenerative course
with death typically by the age of 3 years, most often from respiratory failure.
evidence:
- reference: PMID:28228103
reference_title: "Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "leading to death typically by the age of 3 years, most often from respiratory failure"
explanation: "Documents the fatal infantile prognosis of type A."
diagnosis:
- name: Acid sphingomyelinase enzyme assay
diagnosis_term:
preferred_term: clinical laboratory procedure
term:
id: MAXO:0000006
label: clinical laboratory procedure
description: >-
Demonstration of markedly deficient acid sphingomyelinase activity in peripheral
leukocytes, cultured fibroblasts, or dried blood spots supports the diagnosis.
markers: Markedly reduced acid sphingomyelinase activity.
evidence:
- reference: PMID:38397448
reference_title: "The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann-Pick Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "NPD type A and B are caused by mutations in the gene SMPD1 coding for sphingomyelin phosphodiesterase 1, with a consequent lack of acid sphingomyelinase activity."
explanation: "Deficient acid sphingomyelinase activity is the diagnostic biochemical hallmark."
- name: SMPD1 molecular genetic testing
diagnosis_term:
preferred_term: genetic testing
term:
id: MAXO:0000127
label: genetic testing
description: Confirmatory biallelic SMPD1 sequencing.
evidence:
- reference: PMID:37069638
reference_title: "Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann-Pick disease types A, B and A/B)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Acid Sphingomyelinase Deficiency (ASMD) is a rare autosomal recessive disorder caused by mutations in the SMPD1 gene."
explanation: "SMPD1 sequencing provides molecular confirmation."
differential_diagnoses:
- name: Niemann-Pick disease type B
description: >-
The chronic, non-neuronopathic form of acid sphingomyelinase deficiency, with the same
SMPD1 basis but residual enzyme activity and survival into adulthood.
disease_term:
preferred_term: Niemann-Pick disease type B
term:
id: MONDO:0011871
label: Niemann-Pick disease type B
distinguishing_features:
- Higher residual acid sphingomyelinase activity, with little or no CNS involvement and survival into adulthood.
evidence:
- reference: PMID:28164782
reference_title: "Types A and B Niemann-Pick disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no CNS signs."
explanation: "Type B lacks the profound CNS involvement of type A, distinguishing the two."
- name: Niemann-Pick disease type C
description: >-
A clinically overlapping but biochemically distinct disorder of cholesterol
trafficking (NPC1/NPC2), not caused by acid sphingomyelinase deficiency.
disease_term:
preferred_term: Niemann-Pick disease type C
term:
id: MONDO:0018982
label: Niemann-Pick disease type C
distinguishing_features:
- Caused by defective cholesterol transport (NPC1/NPC2), not SMPD1; acid sphingomyelinase activity is normal.
evidence:
- reference: PMID:28164782
reference_title: "Types A and B Niemann-Pick disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "the second is due to defective function in cholesterol transport (\"type C\" NPD)"
explanation: "Type C is a distinct cholesterol-transport defect, not acid sphingomyelinase deficiency."
treatments:
- name: Supportive Care
description: >-
Because no CNS-directed disease-modifying therapy exists, supportive symptomatic care
(nutritional, respiratory, and palliative support) remains the mainstay for type A.
treatment_term:
preferred_term: Supportive Care
term:
id: NCIT:C15747
label: Supportive Care
evidence:
- reference: PMID:28228103
reference_title: "Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "NPD A is associated with a uniformly devastating disease course"
explanation: "The devastating, untreatable CNS course means care is supportive."
- name: Enzyme Replacement Therapy (olipudase alfa)
description: >-
Olipudase alfa is the first approved disease-modifying therapy for ASMD, but it
addresses only non-CNS (visceral and pulmonary) manifestations and does not cross the
blood-brain barrier, so it does not treat the neurodegeneration of type A.
therapeutic_modality: PROTEIN_REPLACEMENT
treatment_term:
preferred_term: enzyme replacement therapy
term:
id: MAXO:0000933
label: enzyme replacement or supplementation therapy
evidence:
- reference: PMID:38397448
reference_title: "The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann-Pick Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Enzyme replacement therapy with Olipudase α is the first and only approved disease-modifying therapy for patients with ASMD."
explanation: "Olipudase alfa is the approved ERT for ASMD, though limited to non-CNS disease."
definitions:
- name: Clinical case definition of Niemann-Pick disease type A
definition_type: CASE_DEFINITION
description: >-
Niemann-Pick disease type A is the fatal infantile neurovisceral form of acid
sphingomyelinase deficiency, defined by biallelic SMPD1 loss-of-function variants with
profound enzyme deficiency, early hepatosplenomegaly, and rapidly progressive
neurodegeneration.
scope: Disease-level case definition for the severe infantile neuronopathic ASMD subtype.
evidence:
- reference: PMID:37069638
reference_title: "Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann-Pick disease types A, B and A/B)."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Acid Sphingomyelinase Deficiency (ASMD) is a rare autosomal recessive disorder caused by mutations in the SMPD1 gene."
explanation: "Anchors the case definition in the SMPD1/ASMD framework."
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on Niemann-Pick Disease Type A covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.
For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.
Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed
Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Search first: CTD, PubMed, PheGenI, GxE databases
Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC
For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities
For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype
Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser
Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Search first: CDC databases, WHO, PubMed, NHANES
Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON
Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Search first: PubMed, Gene Ontology, Reactome
Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types
Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Search first: OMIM, Orphanet, HPO, PubMed
Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.
Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Search first: NSGC resources, ACMG guidelines, GeneReviews
Search first: Clinical guidelines, FDA approvals, PubMed
Search first: NCBI Taxonomy
Search first: VBO (Vertebrate Breed Ontology)
Search first: NCBI Gene
Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease
This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details
Niemann–Pick disease type A (NPD-A) is the severe, infantile neurovisceral end of acid sphingomyelinase deficiency (ASMD), a rare autosomal recessive lysosomal storage disorder caused by biallelic loss-of-function variants in SMPD1, resulting in profound acid sphingomyelinase (ASM) deficiency and lysosomal accumulation of sphingomyelin with downstream cellular and organ dysfunction. NPD-A typically presents in early infancy with hepatosplenomegaly and rapidly progressive neurodegeneration, with death usually in early childhood. Recent (2023–2024) developments relevant to real-world care include (i) publication of international consensus clinical management guidelines (2023), (ii) broader real-world implementation of olipudase alfa enzyme replacement therapy for non-CNS manifestations of ASMD (not curative for NPD-A neurodegeneration), and (iii) accelerating newborn screening pilots/algorithms incorporating DBS ASM activity + LysoSM second-tier testing + SMPD1 sequencing, with higher-than-clinically-recognized incidence estimates in some settings. (geberhiwot2023consensusclinicalmanagement pages 1-2, mauhin2024acidsphingomyelinasedeficiency pages 11-11, gragnaniello2024newbornscreeningfor pages 3-5, gragnaniello2024newbornscreeningfor pages 1-2)
| Domain | Key details | Evidence/source (with year) |
|---|---|---|
| Disease name / classification | Niemann–Pick disease type A = infantile neurovisceral acid sphingomyelinase deficiency (ASMD); severe neuronopathic end of the ASMD spectrum | 2023 consensus guidelines; 2024 pediatric ASMD review (geberhiwot2023consensusclinicalmanagement pages 1-2, geberhiwot2023consensusclinicalmanagement pages 2-4, lipinski2024chronicacidsphingomyelinase pages 1-2) |
| Identifiers | MONDO: MONDO:0009756 (Niemann-Pick disease type A); OMIM numbers cited in 2023 guidelines header for ASMD/Niemann–Pick types A/B: 257200 and 607616 | Open Targets disease mapping; 2023 guidelines (OpenTargets Search: Niemann-Pick disease type A-SMPD1, geberhiwot2023consensusclinicalmanagement pages 1-2) |
| Causative gene | SMPD1 (sphingomyelin phosphodiesterase 1); loss-of-function variants cause acid sphingomyelinase deficiency | 2023 guidelines; 2017 review (geberhiwot2023consensusclinicalmanagement pages 2-4, schuchman2017typesaand pages 1-3) |
| Inheritance | Autosomal recessive; biallelic pathogenic SMPD1 variants | 2023 guidelines; 2024 pediatric ASMD review (geberhiwot2023consensusclinicalmanagement pages 1-2, lipinski2024chronicacidsphingomyelinase pages 1-2) |
| Core biochemical defect | Deficient lysosomal acid sphingomyelinase (ASM) activity causes sphingomyelin accumulation with secondary lipid accumulation including cholesterol | 2023 guidelines; 2024 review (geberhiwot2023consensusclinicalmanagement pages 4-5, tirelli2024thegeneticbasis pages 1-3) |
| Hallmark early visceral features | Hepatosplenomegaly in early infancy; often presents at 2–4 months; splenomegaly is a key clue | 2017 burden review; 2023 guidelines (mcgovern2017diseasemanifestationsand pages 2-3, geberhiwot2023consensusclinicalmanagement pages 4-5) |
| Hallmark neurologic course / onset | Development may be initially normal, then psychomotor delay/regression begins in the first year; neurologic symptoms median ~7 months; regression often noted in the second 6 months of life | 2017 burden review; 2024 pediatric ASMD review (mcgovern2017diseasemanifestationsand pages 2-3, lipinski2024chronicacidsphingomyelinase pages 1-2) |
| Other common features | Cherry-red macula often present by 12 months; hypotonia, growth failure/failure to thrive, rapidly progressive neurodegeneration, respiratory involvement | 2017 burden review; 2024 review (mcgovern2017diseasemanifestationsand pages 2-3, tirelli2024thegeneticbasis pages 1-3) |
| Prognosis | Uniformly severe, rapidly progressive infantile disorder; patients rarely survive beyond 2–3 years | 2017 review; 2023 guidelines (schuchman2017typesaand pages 1-3, geberhiwot2023consensusclinicalmanagement pages 2-4) |
| Survival statistics (French cohort, 2024) | Type A cohort n=15; median age at symptom onset 6.0 months (3.0–18.0), diagnosis 8.0 months (1.0–18.0), death 1 year (0–3.6); median survival from birth 2.0 years (95% CI 1.8–2.7); mortality 14/15 (93.3%) at study cut-off | Mauhin et al., Orphanet J Rare Dis 2024 (mauhin2024acidsphingomyelinasedeficiency pages 1-2, mauhin2024acidsphingomyelinasedeficiency pages 3-5) |
| Population genetics / founder effect | Ashkenazi Jewish carrier frequency reported around 1:100–1:200, with estimated disease prevalence 1:40,000–1:200,000 in that population | 2023 guidelines (geberhiwot2023consensusclinicalmanagement pages 4-5) |
| Diagnostic enzyme testing | ASM activity can be measured in peripheral blood leukocytes/lymphocytes, cultured skin fibroblasts, or dried blood spots; marked deficiency supports diagnosis | 2017 review; 2024 review/guidance (mcgovern2017diseasemanifestationsand pages 2-3, alagia2024acidsphingomyelinasedeficiencya pages 26-27) |
| Diagnostic molecular testing | Confirmatory SMPD1 sequencing; NGS/Sanger used, with MLPA/WGS considered if needed | 2017 review; 2024 review/guidance (mcgovern2017diseasemanifestationsand pages 2-3, alagia2024acidsphingomyelinasedeficiency pages 26-27) |
| Biomarkers | Lyso-sphingomyelin (LysoSM) and LysoSM-509 are useful ASMD biomarkers; elevated in DBS and plasma and useful for screening/triage | 2024 Polish update; 2024 review/guidance (lipinski2024chronicacidsphingomyelinase pages 1-2, alagia2024acidsphingomyelinasedeficiencya pages 26-27) |
| Newborn screening algorithm (Italy) | First-tier DBS ASM activity by LC-MS/MS; monthly recalculated 0.2 MoM cutoff; second-tier LysoSM on same DBS; abnormal samples undergo SMPD1 genotyping | Gragnaniello et al., 2024 (gragnaniello2024newbornscreeningfor pages 3-5, gragnaniello2024newbornscreeningfor pages 5-6) |
| Newborn screening cutoff / abnormal biomarker | Italian NBS used LysoSM > 51.68 nmol/L as abnormal in second-tier testing | Gragnaniello et al., 2024 (gragnaniello2024newbornscreeningfor pages 3-5) |
| Newborn screening performance (Italy) | 275,011 newborns screened; 2 screen-positive/confirmed cases; estimated incidence 1:137,506; reported PPV 100% in study summary/table | Gragnaniello et al., 2024 (gragnaniello2024newbornscreeningfor pages 2-3, gragnaniello2024newbornscreeningfor pages 1-2) |
| 2023 care standard | First international consensus management guidelines published for ASMD, addressing diagnosis, multidisciplinary care, and standard-of-care gaps | Geberhiwot et al., 2023 (geberhiwot2023consensusclinicalmanagement pages 1-2) |
| Approved disease-modifying therapy | Olipudase alfa (Xenpozyme) is the first approved disease-modifying therapy for ASMD, but only for non-CNS manifestations; supportive care remains the mainstay for type A | 2024 review; 2023 guidelines; Mauhin 2024 reference summary (tirelli2024thegeneticbasis pages 1-3, geberhiwot2023consensusclinicalmanagement pages 1-2, mauhin2024acidsphingomyelinasedeficiency pages 11-11) |
| Why olipudase alfa is limited in type A | Enzyme replacement improves visceral disease but is limited by lack of meaningful CNS penetration/blood–brain barrier barrier, so infantile neurovisceral type A is not adequately addressed | 2024 reviews (naffadi2024neimannpickdiseasesbeyonda pages 6-7, naffadi2024neimannpickdiseasesbeyond pages 6-7) |
| Expanded access / real-world implementation | Compassionate-use olipudase alfa program for chronic ASMD: NCT04877132; excludes infantile-onset/genotype-compatible type A and includes type A/B or B patients with chronic disease | ClinicalTrials.gov expanded access (NCT04877132 chunk 1) |
| Pivotal adult olipudase trial | ASCEND trial NCT02004691: phase 2/3 randomized placebo-controlled adult study; 36 participants; primary endpoints included spleen volume by MRI and DLCO | ClinicalTrials.gov; 2024 review (NCT02004691 chunk 1, alagia2024acidsphingomyelinasedeficiencya pages 27-29) |
| Pediatric olipudase development | ASCEND-Peds / NCT02292654: phase 1/2 pediatric repeat-dose olipudase study; 20 participants | ClinicalTrials.gov registry summary (alagia2024acidsphingomyelinasedeficiencya pages 27-29) |
| Real-world early access study | OPERA France / NCT05359276: observational real-world cohort (n=40) evaluating lung, spleen, liver outcomes, safety, immunogenicity, biomarkers, and treatment-use patterns with olipudase alfa | ClinicalTrials.gov (NCT05359276 chunk 1) |
| Infant/toddler post-approval study | NCT06192576: real-world long-term safety and immunogenicity study of olipudase alfa in pediatric patients <2 years with ASMD | ClinicalTrials.gov (NCT06192576 chunk 2) |
| Research pipeline beyond ERT | Gene therapy is under active preclinical/early clinical investigation for ASMD because current ERT does not solve CNS disease in type A | 2024 reviews (naffadi2024neimannpickdiseasesbeyond pages 6-7) |
Table: This table summarizes the most actionable disease-characteristics facts for Niemann–Pick disease type A, including identifiers, genetics, phenotype, prognosis, diagnostics, and 2023–2024 therapeutic/screening developments. It is designed for rapid knowledge-base population with source-linked evidence.
Niemann–Pick disease type A (NPD-A) is historically one of the “Niemann–Pick types A and B,” but is now more precisely classified within acid sphingomyelinase deficiency (ASMD) because both type A and type B are caused by pathogenic variants in SMPD1 encoding ASM. (schuchman2017typesaand pages 1-3)
Clinically, NPD-A represents a “fatal infantile neurovisceral disorder” on a continuum of ASMD phenotypes. (geberhiwot2023consensusclinicalmanagement pages 1-2)
Not found in the retrieved full-text evidence: ICD-10/ICD-11 codes, MeSH identifiers, and Orphanet disease IDs were not explicitly extractable from the available excerpts; therefore, they are not asserted here.
Most disease-level statements here derive from aggregated resources (international consensus guidelines, cohort studies, and reviews) rather than single EHR records. (geberhiwot2023consensusclinicalmanagement pages 1-2, mauhin2024acidsphingomyelinasedeficiency pages 1-2)
Primary cause (genetic/mechanistic): NPD-A is caused by biallelic pathogenic variants in SMPD1, leading to severe deficiency of lysosomal acid sphingomyelinase activity. (geberhiwot2023consensusclinicalmanagement pages 2-4, geberhiwot2023consensusclinicalmanagement pages 4-5)
Quote (guidelines): ASMD is “a rare autosomal recessive disorder caused by pathogenic variants/mutations in the SMPD1 gene.” (geberhiwot2023consensusclinicalmanagement pages 1-2)
No validated protective factors or gene–environment interactions for NPD-A were identified in the retrieved 2023–2024 evidence.
NPD-A is characterized by early visceral disease followed by rapidly progressive neurodegeneration in infancy.
Early visceral presentation: In a synthesis of ASMD manifestations, NPD-A infants “presented with hepatosplenomegaly at 2–4 months of age.” (mcgovern2017diseasemanifestationsand pages 2-3)
Neurologic onset/progression: Neurologic symptoms were reported as first detected around “a median age of 7 months,” with severe progressive neurodegeneration in the first year of life. (mcgovern2017diseasemanifestationsand pages 2-3)
Ophthalmologic: “Macular cherry-red spots were detectable in all infants by 12 months.” (mcgovern2017diseasemanifestationsand pages 2-3)
(These are ontology mappings for knowledge-base structure; they are not claims of frequency unless stated.) - Hepatosplenomegaly: HP:0001433 - Splenomegaly: HP:0001744 - Hepatomegaly: HP:0002240 - Failure to thrive: HP:0001508 - Developmental regression: HP:0002376 - Hypotonia: HP:0001252 - Cherry-red spot of the macula: HP:0001103 - Neurodegeneration: HP:0002180
The retrieved evidence emphasizes profound disability and rapid neurodegenerative decline in type A (fatal infantile course), implying major impact on feeding, respiration, neurodevelopment, and caregiver burden, though standardized QoL instruments were not found in the provided excerpts. (mcgovern2017diseasemanifestationsand pages 2-3, geberhiwot2023consensusclinicalmanagement pages 2-4)
The 2023 consensus guidelines note a large allelic heterogeneity with “over 250 SMPD1 variants” reported across ASMD. (geberhiwot2023consensusclinicalmanagement pages 2-4)
The mechanistic consequence is loss of ASM enzymatic activity leading to storage of sphingomyelin and secondary lipids in lysosomes, with prominent involvement of monocyte/macrophage-lineage cells (lipid-laden macrophages) in organs such as liver and spleen. (geberhiwot2023consensusclinicalmanagement pages 4-5)
No specific modifier genes, epigenetic mechanisms, or large chromosomal abnormalities were extractable from the retrieved evidence excerpts.
NPD-A is not primarily driven by environmental or infectious causes in the retrieved evidence; it is an inherited lysosomal enzyme deficiency. (geberhiwot2023consensusclinicalmanagement pages 1-2)
1) Upstream trigger: Biallelic SMPD1 loss-of-function variants (geberhiwot2023consensusclinicalmanagement pages 2-4) 2) Primary biochemical defect: Severe deficiency of lysosomal acid sphingomyelinase activity (geberhiwot2023consensusclinicalmanagement pages 4-5) 3) Storage pathology: Lysosomal accumulation of sphingomyelin and “secondary lipids (notably cholesterol)” (geberhiwot2023consensusclinicalmanagement pages 4-5) 4) Cellular/tissue effects: Lipid-laden “foam cells” and macrophage storage pathology across organs (mcgovern2017diseasemanifestationsand pages 2-3, geberhiwot2023consensusclinicalmanagement pages 4-5) 5) Clinical manifestations: Early hepatosplenomegaly (months), progressive neurologic deterioration (infancy), respiratory complications and early childhood mortality (mcgovern2017diseasemanifestationsand pages 2-3, geberhiwot2023consensusclinicalmanagement pages 2-4)
Recent reviews emphasize that enzyme replacement therapy can improve visceral storage but is limited by inadequate CNS delivery: “overcoming the blood brain barrier to ensure sufficient enzyme penetration remains a hurdle.” (naffadi2024neimannpickdiseasesbeyonda pages 6-7)
Commonly involved organs in ASMD (including type A) include liver, spleen, lungs, bone marrow, and (in severe cases) neurons/CNS. (mcgovern2017diseasemanifestationsand pages 2-3, geberhiwot2023consensusclinicalmanagement pages 4-5)
Primary pathological compartment: lysosomes (GO:0005764). (geberhiwot2023consensusclinicalmanagement pages 4-5)
NPD-A onset is in infancy with early visceromegaly; symptom onset in the French cohort was median 6.0 months. (mauhin2024acidsphingomyelinasedeficiency pages 3-5)
Progression is rapidly neurodegenerative. The 2023 consensus describes type A as “rapidly progressive and neurodegenerative,” with deaths often by ~3 years. (geberhiwot2023consensusclinicalmanagement pages 2-4)
ASMD/NPD-A is autosomal recessive. (geberhiwot2023consensusclinicalmanagement pages 1-2, lipinski2024chronicacidsphingomyelinase pages 1-2)
Quote (Japan underdiagnosis interpretation): “Our data also suggest that there are more patients with a milder form of ASMD and nonspecific clinical findings who have not yet been diagnosed.” (sako2024allelefrequencyof pages 1-2)
1) Enzyme assay: ASM activity measurement in leukocytes/lymphocytes or cultured fibroblasts; ASM activity can also be measured in dried blood spots (DBS). (mcgovern2017diseasemanifestationsand pages 2-3, alagia2024acidsphingomyelinasedeficiencya pages 26-27) 2) Molecular confirmation: SMPD1 sequencing; guidelines and reviews emphasize genetic confirmation. (mcgovern2017diseasemanifestationsand pages 2-3, alagia2024acidsphingomyelinasedeficiency pages 26-27) 3) Biomarkers: Lyso-sphingomyelin (LysoSM) and LysoSM-509 elevated in DBS/plasma; used as screening and monitoring biomarkers. (lipinski2024chronicacidsphingomyelinase pages 1-2, alagia2024acidsphingomyelinasedeficiencya pages 26-27)
Italy newborn screening protocol (publication date Dec 2024; https://doi.org/10.3390/ijns10040079): - First-tier: DBS ASM activity by LC–MS/MS (NeoLSD® assay), cutoff recalculated monthly (0.2 MoM). (gragnaniello2024newbornscreeningfor pages 3-5) - Second-tier: LysoSM quantification on the same DBS; “LysoSM > 51.68 nmol/L considered abnormal.” (gragnaniello2024newbornscreeningfor pages 3-5) - Third-tier/confirmation: SMPD1 genotyping via NGS of exons and exon–intron boundaries. (gragnaniello2024newbornscreeningfor pages 3-5)
The retrieved excerpts emphasize that ASMD can be misdiagnosed/delayed due to heterogeneity and overlap with other causes of hepatosplenomegaly and storage pathology, but specific differential diagnosis lists were not extractable from the available guideline pages. (geberhiwot2023consensusclinicalmanagement pages 1-2)
France retrospective survival study (Orphanet J Rare Dis; Aug 2024; https://doi.org/10.1186/s13023-024-03234-6): - Type A sample: n=15 medical records. (mauhin2024acidsphingomyelinasedeficiency pages 1-2) - “Median [range] age at diagnosis was 8.0 [1.0–18.0] months (type A).” (mauhin2024acidsphingomyelinasedeficiency pages 1-2) - “The median [range] age at death for patients with ASMD type A (n = 14) was 1 [0–3.6] year.” (mauhin2024acidsphingomyelinasedeficiency pages 1-2) - “The median [95% CI] survival age from birth in patients with ASMD type A… was 2.0 [1.8–2.7] years.” (mauhin2024acidsphingomyelinasedeficiency pages 1-2) - Mortality burden: 14/15 (93.3%) at study cut-off. (mauhin2024acidsphingomyelinasedeficiency pages 3-5)
These statistics are consistent with earlier aggregated summaries that NPD-A “rarely survive beyond 2–3 years of age.” (schuchman2017typesaand pages 1-3)
The 2023 consensus guidelines emphasize that supportive symptomatic care remains the mainstay of management “definitely in those with type A,” reflecting the lack of disease-modifying CNS-directed therapy. (geberhiwot2023consensusclinicalmanagement pages 1-2)
Suggested MAXO terms (supportive care concepts; non-exhaustive): nutritional support, respiratory support, palliative care, physical therapy.
State of the art (2023–2024): Olipudase alfa is described as the first approved disease-modifying therapy for ASMD, but approvals and clinical trials primarily address non-CNS manifestations (visceral/lung). (tirelli2024thegeneticbasis pages 1-3, mauhin2024acidsphingomyelinasedeficiency pages 11-11)
Real-world implementations / programs and trials (ClinicalTrials.gov): - ASCEND pivotal adult trial: NCT02004691 (Phase 2/3; randomized placebo-controlled; 36 adults; endpoints included spleen volume by MRI and DLCO; results posted 2022-05-24). (NCT02004691 chunk 1) - Expanded access / compassionate use: NCT04877132 (first posted 2021-05-07; last update 2022-09-19). Notably, it excludes “infantile-onset ASMD (genotype compatible with ASMD type A)” and targets chronic disease populations. (NCT04877132 chunk 1) - Real-world early access cohort (France): NCT05359276 (OPERA; observational; enrolled 40; start 2022-06-10; primary outcomes include change in DLCO, spleen size, liver size at 24 months; includes biomarkers such as lysosphingomyelin). (NCT05359276 chunk 1) - Post-approval very young pediatrics: NCT06192576 (real-world long-term safety and immunogenicity in ASMD patients <2 years; Sanofi; data access via Vivli). (NCT06192576 chunk 2)
The major limitation for NPD-A is CNS disease, because systemic enzyme does not adequately cross the blood–brain barrier; recent reviews highlight that BBB penetration “remains a hurdle.” (naffadi2024neimannpickdiseasesbeyonda pages 6-7)
Recent reviews emphasize active investigation of gene therapy approaches (preclinical and early clinical efforts) as a potential strategy to address limitations of systemic ERT for neuronopathic disease. (naffadi2024neimannpickdiseasesbeyond pages 6-7)
For autosomal recessive Mendelian disorders such as NPD-A, prevention is primarily through carrier detection and reproductive options (e.g., prenatal diagnosis). Prenatal diagnosis is referenced in ASMD clinical literature as feasible via enzymatic and molecular analysis (e.g., chorionic villi approaches are discussed in ASMD diagnostic context). (mcgovern2017diseasemanifestationsand pages 2-3)
No naturally occurring veterinary NPD-A evidence was extractable from the retrieved evidence excerpts.
The retrieved evidence excerpts did not provide detailed, citable descriptions of specific ASMD/NPD-A animal models (e.g., Smpd1 knockout mouse phenotypes) beyond general statements that gene therapy is being investigated in animals. (naffadi2024neimannpickdiseasesbeyond pages 6-7)
1) International consensus guidelines (2023): First international consensus clinical management guidelines for ASMD were developed using systematic review and structured guideline methods (AGREE II / GRADE/Delphi), explicitly aiming to reduce misdiagnosis and standardize multidisciplinary care. This is a key authoritative source for “expert opinion” statements in an ultra-rare disease with limited RCT evidence. (geberhiwot2023consensusclinicalmanagement pages 1-2, geberhiwot2023consensusclinicalmanagement pages 2-4)
2) New survival data (2024): The French retrospective survival study quantifies NPD-A mortality and survival distribution in a national multi-hospital sample, including median survival from birth of ~2 years. (mauhin2024acidsphingomyelinasedeficiency pages 1-2)
3) Newborn screening evidence (2024): The Italian NBS study demonstrates feasibility of a two-tier biochemical algorithm (ASM activity + LysoSM) plus SMPD1 sequencing, yielding an estimated incidence (1:137,506) that the authors interpret as potentially higher than clinically reported. (gragnaniello2024newbornscreeningfor pages 1-2)
4) Population-genetic incidence estimates (2024): Japanese genome-resource aggregation suggests higher-than-expected carrier frequency and predicted disease frequency, supporting the expert view that ASMD may be underdiagnosed, particularly in milder phenotypes. (sako2024allelefrequencyof pages 1-2)
5) Therapeutic era shift (2023–2024): Olipudase alfa implementation has moved beyond pivotal trials into expanded access and real-world cohorts, focusing on visceral/lung endpoints and immunogenicity monitoring—while consensus documents still emphasize supportive care for NPD-A due to CNS limitations. (geberhiwot2023consensusclinicalmanagement pages 1-2, NCT05359276 chunk 1, NCT04877132 chunk 1)
Several template fields (ICD-10/ICD-11/MeSH/Orphanet IDs, comprehensive differential diagnosis lists, detailed model-organism phenotypes, and a structured treatment algorithm specific to type A beyond supportive care) were not explicitly present in the retrieved full-text excerpts; they are therefore not asserted beyond what is directly supported by citations above. (geberhiwot2023consensusclinicalmanagement pages 1-2)
References
(geberhiwot2023consensusclinicalmanagement pages 1-2): Tarekegn Geberhiwot, Melissa Wasserstein, Subadra Wanninayake, Shaun Christopher Bolton, Andrea Dardis, Anna Lehman, Olivier Lidove, Charlotte Dawson, Roberto Giugliani, Jackie Imrie, Justin Hopkin, James Green, Daniel de Vicente Corbeira, Shyam Madathil, Eugen Mengel, Fatih Ezgü, Magali Pettazzoni, Barbara Sjouke, Carla Hollak, Marie T. Vanier, Margaret McGovern, and Edward Schuchman. Consensus clinical management guidelines for acid sphingomyelinase deficiency (niemann–pick disease types a, b and a/b). Orphanet Journal of Rare Diseases, Apr 2023. URL: https://doi.org/10.1186/s13023-023-02686-6, doi:10.1186/s13023-023-02686-6. This article has 105 citations and is from a peer-reviewed journal.
(mauhin2024acidsphingomyelinasedeficiency pages 11-11): Wladimir Mauhin, Nathalie Guffon, Marie T. Vanier, Roseline Froissart, Aline Cano, Claire Douillard, Christian Lavigne, Bénédicte Héron, Nadia Belmatoug, Yurdagül Uzunhan, Didier Lacombe, Thierry Levade, Aymeric Duvivier, Ruth Pulikottil-Jacob, Fernando Laredo, Samia Pichard, Olivier Lidove, Marie-Thérèse Abi-Wardé, Marc Berger, Emilie Berthoux, Aurélie Cabannes-Hamy, Fabrice Camou, Pascal Cathebras, Vincent Grobost, Jérémy Keraen, Alice Kuster, Bertrand Lioger, Anas Mehdaoui, Claire Merlot, Martin Michaud, Martine-Louise Reynaud-Gaubert, Fréderic Schlemmer, Amélie Servettaz, Chloé Stavris, and Sébastien Trouillier. Acid sphingomyelinase deficiency in france: a retrospective survival study. Orphanet Journal of Rare Diseases, Aug 2024. URL: https://doi.org/10.1186/s13023-024-03234-6, doi:10.1186/s13023-024-03234-6. This article has 10 citations and is from a peer-reviewed journal.
(gragnaniello2024newbornscreeningfor pages 3-5): Vincenza Gragnaniello, Chiara Cazzorla, Daniela Gueraldi, Christian Loro, Elena Porcù, Leonardo Salviati, Alessandro P. Burlina, and Alberto B. Burlina. Newborn screening for acid sphingomyelinase deficiency: prevalence and genotypic findings in italy. International Journal of Neonatal Screening, 10:79, Dec 2024. URL: https://doi.org/10.3390/ijns10040079, doi:10.3390/ijns10040079. This article has 4 citations.
(gragnaniello2024newbornscreeningfor pages 1-2): Vincenza Gragnaniello, Chiara Cazzorla, Daniela Gueraldi, Christian Loro, Elena Porcù, Leonardo Salviati, Alessandro P. Burlina, and Alberto B. Burlina. Newborn screening for acid sphingomyelinase deficiency: prevalence and genotypic findings in italy. International Journal of Neonatal Screening, 10:79, Dec 2024. URL: https://doi.org/10.3390/ijns10040079, doi:10.3390/ijns10040079. This article has 4 citations.
(geberhiwot2023consensusclinicalmanagement pages 2-4): Tarekegn Geberhiwot, Melissa Wasserstein, Subadra Wanninayake, Shaun Christopher Bolton, Andrea Dardis, Anna Lehman, Olivier Lidove, Charlotte Dawson, Roberto Giugliani, Jackie Imrie, Justin Hopkin, James Green, Daniel de Vicente Corbeira, Shyam Madathil, Eugen Mengel, Fatih Ezgü, Magali Pettazzoni, Barbara Sjouke, Carla Hollak, Marie T. Vanier, Margaret McGovern, and Edward Schuchman. Consensus clinical management guidelines for acid sphingomyelinase deficiency (niemann–pick disease types a, b and a/b). Orphanet Journal of Rare Diseases, Apr 2023. URL: https://doi.org/10.1186/s13023-023-02686-6, doi:10.1186/s13023-023-02686-6. This article has 105 citations and is from a peer-reviewed journal.
(lipinski2024chronicacidsphingomyelinase pages 1-2): Patryk Lipiński, Agnieszka Ługowska, and Anna Tylki-Szymańska. Chronic acid sphingomyelinase deficiency diagnosed in infancy/childhood in polish patients: 2024 update. Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 33:1163-1168, Oct 2024. URL: https://doi.org/10.17219/acem/193696, doi:10.17219/acem/193696. This article has 1 citations.
(OpenTargets Search: Niemann-Pick disease type A-SMPD1): Open Targets Query (Niemann-Pick disease type A-SMPD1, 1 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(schuchman2017typesaand pages 1-3): Edward H. Schuchman and Robert J. Desnick. Types a and b niemann-pick disease. Molecular genetics and metabolism, 120 1-2:27-33, Jan 2017. URL: https://doi.org/10.1016/j.ymgme.2016.12.008, doi:10.1016/j.ymgme.2016.12.008. This article has 412 citations and is from a peer-reviewed journal.
(geberhiwot2023consensusclinicalmanagement pages 4-5): Tarekegn Geberhiwot, Melissa Wasserstein, Subadra Wanninayake, Shaun Christopher Bolton, Andrea Dardis, Anna Lehman, Olivier Lidove, Charlotte Dawson, Roberto Giugliani, Jackie Imrie, Justin Hopkin, James Green, Daniel de Vicente Corbeira, Shyam Madathil, Eugen Mengel, Fatih Ezgü, Magali Pettazzoni, Barbara Sjouke, Carla Hollak, Marie T. Vanier, Margaret McGovern, and Edward Schuchman. Consensus clinical management guidelines for acid sphingomyelinase deficiency (niemann–pick disease types a, b and a/b). Orphanet Journal of Rare Diseases, Apr 2023. URL: https://doi.org/10.1186/s13023-023-02686-6, doi:10.1186/s13023-023-02686-6. This article has 105 citations and is from a peer-reviewed journal.
(tirelli2024thegeneticbasis pages 1-3): Claudio Tirelli, Ornella Rondinone, Marta Italia, Sabrina Mira, Luca Alessandro Belmonte, Mauro De Grassi, Gabriele Guido, Sara Maggioni, Michele Mondoni, Monica Rosa Miozzo, and Stefano Centanni. The genetic basis, lung involvement, and therapeutic options in niemann–pick disease: a comprehensive review. Biomolecules, 14:211, Feb 2024. URL: https://doi.org/10.3390/biom14020211, doi:10.3390/biom14020211. This article has 35 citations.
(mcgovern2017diseasemanifestationsand pages 2-3): Margaret M. McGovern, Ruzan Avetisyan, Bernd-Jan Sanson, and Olivier Lidove. Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (asmd). Orphanet Journal of Rare Diseases, Feb 2017. URL: https://doi.org/10.1186/s13023-017-0572-x, doi:10.1186/s13023-017-0572-x. This article has 220 citations and is from a peer-reviewed journal.
(mauhin2024acidsphingomyelinasedeficiency pages 1-2): Wladimir Mauhin, Nathalie Guffon, Marie T. Vanier, Roseline Froissart, Aline Cano, Claire Douillard, Christian Lavigne, Bénédicte Héron, Nadia Belmatoug, Yurdagül Uzunhan, Didier Lacombe, Thierry Levade, Aymeric Duvivier, Ruth Pulikottil-Jacob, Fernando Laredo, Samia Pichard, Olivier Lidove, Marie-Thérèse Abi-Wardé, Marc Berger, Emilie Berthoux, Aurélie Cabannes-Hamy, Fabrice Camou, Pascal Cathebras, Vincent Grobost, Jérémy Keraen, Alice Kuster, Bertrand Lioger, Anas Mehdaoui, Claire Merlot, Martin Michaud, Martine-Louise Reynaud-Gaubert, Fréderic Schlemmer, Amélie Servettaz, Chloé Stavris, and Sébastien Trouillier. Acid sphingomyelinase deficiency in france: a retrospective survival study. Orphanet Journal of Rare Diseases, Aug 2024. URL: https://doi.org/10.1186/s13023-024-03234-6, doi:10.1186/s13023-024-03234-6. This article has 10 citations and is from a peer-reviewed journal.
(mauhin2024acidsphingomyelinasedeficiency pages 3-5): Wladimir Mauhin, Nathalie Guffon, Marie T. Vanier, Roseline Froissart, Aline Cano, Claire Douillard, Christian Lavigne, Bénédicte Héron, Nadia Belmatoug, Yurdagül Uzunhan, Didier Lacombe, Thierry Levade, Aymeric Duvivier, Ruth Pulikottil-Jacob, Fernando Laredo, Samia Pichard, Olivier Lidove, Marie-Thérèse Abi-Wardé, Marc Berger, Emilie Berthoux, Aurélie Cabannes-Hamy, Fabrice Camou, Pascal Cathebras, Vincent Grobost, Jérémy Keraen, Alice Kuster, Bertrand Lioger, Anas Mehdaoui, Claire Merlot, Martin Michaud, Martine-Louise Reynaud-Gaubert, Fréderic Schlemmer, Amélie Servettaz, Chloé Stavris, and Sébastien Trouillier. Acid sphingomyelinase deficiency in france: a retrospective survival study. Orphanet Journal of Rare Diseases, Aug 2024. URL: https://doi.org/10.1186/s13023-024-03234-6, doi:10.1186/s13023-024-03234-6. This article has 10 citations and is from a peer-reviewed journal.
(alagia2024acidsphingomyelinasedeficiencya pages 26-27): M ALAGIA, E CIRILLO, and A TARALLO. Acid sphingomyelinase deficiency: a complex and rare disorder that needs clinicians'awareness. Unknown journal, 2024.
(alagia2024acidsphingomyelinasedeficiency pages 26-27): M ALAGIA, E CIRILLO, and A TARALLO. Acid sphingomyelinase deficiency: a complex and rare disorder that needs clinicians'awareness. Unknown journal, 2024.
(gragnaniello2024newbornscreeningfor pages 5-6): Vincenza Gragnaniello, Chiara Cazzorla, Daniela Gueraldi, Christian Loro, Elena Porcù, Leonardo Salviati, Alessandro P. Burlina, and Alberto B. Burlina. Newborn screening for acid sphingomyelinase deficiency: prevalence and genotypic findings in italy. International Journal of Neonatal Screening, 10:79, Dec 2024. URL: https://doi.org/10.3390/ijns10040079, doi:10.3390/ijns10040079. This article has 4 citations.
(gragnaniello2024newbornscreeningfor pages 2-3): Vincenza Gragnaniello, Chiara Cazzorla, Daniela Gueraldi, Christian Loro, Elena Porcù, Leonardo Salviati, Alessandro P. Burlina, and Alberto B. Burlina. Newborn screening for acid sphingomyelinase deficiency: prevalence and genotypic findings in italy. International Journal of Neonatal Screening, 10:79, Dec 2024. URL: https://doi.org/10.3390/ijns10040079, doi:10.3390/ijns10040079. This article has 4 citations.
(naffadi2024neimannpickdiseasesbeyonda pages 6-7): HM Naffadi. Neimann-pick diseases: beyond lipid accumulation–genetic, diagnostics, and therapeutic strategies. Unknown journal, 2024.
(naffadi2024neimannpickdiseasesbeyond pages 6-7): HM Naffadi. Neimann-pick diseases: beyond lipid accumulation–genetic, diagnostics, and therapeutic strategies. Unknown journal, 2024.
(NCT04877132 chunk 1): Compassionate Use Program for Olipudase Alfa Enzyme Replacement Therapy for Patients With Chronic Acid Sphingomyelinase Deficiency (ASMD). Sanofi. ClinicalTrials.gov Identifier: NCT04877132
(NCT02004691 chunk 1): Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency. Genzyme, a Sanofi Company. 2015. ClinicalTrials.gov Identifier: NCT02004691
(alagia2024acidsphingomyelinasedeficiencya pages 27-29): M ALAGIA, E CIRILLO, and A TARALLO. Acid sphingomyelinase deficiency: a complex and rare disorder that needs clinicians'awareness. Unknown journal, 2024.
(NCT05359276 chunk 1): Data Analysis of Adult and Pediatric Participants With Acid Sphingomyelinase Deficiency (ASMD) on Early Access to Olipudase Alfa in France. Sanofi. 2022. ClinicalTrials.gov Identifier: NCT05359276
(NCT06192576 chunk 2): A Real-world Long-term Safety and Immunogenicity Study of Olipudase Alfa Therapy in Pediatric Patients Less Than 2 Years of Age With Acid Sphingomyelinase Deficiency (ASMD). Sanofi. 2024. ClinicalTrials.gov Identifier: NCT06192576
(sako2024allelefrequencyof pages 1-2): Shuhei Sako, Kimihiko Oishi, Hiroyuki Ida, and Eri Imagawa. Allele frequency of pathogenic variants causing acid sphingomyelinase deficiency and gaucher disease in the general japanese population. Human Genome Variation, Jun 2024. URL: https://doi.org/10.1038/s41439-024-00282-z, doi:10.1038/s41439-024-00282-z. This article has 3 citations.