Acatalasia

Mendelian MONDO:0013571 Pathograph 18 Show in embeddings browser Inborn Error of Metabolism

Acatalasia (acatalasemia) is a rare autosomal recessive inborn error caused by biallelic CAT pathogenic variants and defined biochemically by marked, often near-total deficiency of catalase activity in erythrocytes. Most affected people are clinically asymptomatic. In the symptomatic oral presentation historically called Takahara disease, hydrogen peroxide produced by oral microorganisms at gingival wounds is not efficiently detoxified. A proposed local blood-oxidation and oxygen-deprivation mechanism may then promote necrotic ulceration, gangrene, severe periodontitis, and tooth loss. Exogenous hydrogen peroxide is an important methemoglobinemia hazard. An association with type 2 diabetes has been reported in selected populations, but its generalizability and causal mechanism remain uncertain.

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1
Mappings
1
Inheritance
8
Pathophys.
7
Phenotypes
2
Hypotheses
18
Pathograph
1
Genes
4
Medical Actions
1
Differentials
9
References
🏷

Classifications

Harrison's Part
GENETICS ENVIRONMENT DISEASE
ICIMD (Inherited Metabolic Disorders)
intermediary metabolism miscellaneous
🔗

Mappings

MONDO
MONDO:0013571 acatalasia
skos:exactMatch MONDO
MONDO:0013571 is the canonical acatalasia concept used by this entry.
👪

Inheritance

1
Autosomal recessive inheritance HP:0000007
Autosomal recessive inheritance
Show evidence (2 references)
PMID:24522161 SUPPORT Human Clinical
"Acatalasemia is a rare genetic catalase deficiency that is inherited as an autosomal recessive trait."
The report explicitly states the autosomal recessive inheritance pattern.
PMID:120431 SUPPORT Human Clinical
"The inheritance pattern in the kindred was compatible with an autosomal recessive disorder."
The multigeneration pedigree independently supports recessive inheritance.
◈

Mechanistic Hypotheses

2
Canonical CAT Deficiency and Oral Injury Model
canonical_cat_deficiency_oral_injury_model CANONICAL
Evidence balance 2 support
Biallelic CAT variants produce marked erythrocyte catalase deficiency and impaired hydrogen peroxide decomposition. Most affected people remain asymptomatic, but at gingival wounds hydrogen peroxide-producing oral microorganisms can create a local oxidant burden. Historical patient-blood agar experiments propose that oxyhemoglobin oxidation, reduced oxygen availability, and a self-reinforcing necrotic ulcer and periodontal-injury cycle follow. The same catalase deficit makes exogenous hydrogen peroxide an acute methemoglobinemia hazard.
The oral co-trigger is conditional rather than inevitable. The graph does not treat acatalasia as a generalized peroxisome-biogenesis disorder and does not infer chronic hemolysis or universal systemic oxidative injury.
Pathograph links
Biallelic CAT Pathogenic Variation -> Marked Erythrocyte Catalase Deficiency DIRECT Biallelic CAT dysfunction produces the marked erythrocyte enzyme deficiency that defines acatalasia.
Marked Erythrocyte Catalase Deficiency -> Impaired Hydrogen Peroxide Detoxification DIRECT Catalase deficiency reduces enzymatic decomposition of hydrogen peroxide.
Marked Erythrocyte Catalase Deficiency -> Reduced circulating catalase activity DIRECT Markedly reduced erythrocyte enzyme activity is the defining measurable phenotype.
Impaired Hydrogen Peroxide Detoxification -> Oral Plaque Hydrogen Peroxide at Gingival Wounds DIRECT Failure to degrade microorganism-derived hydrogen peroxide permits persistence at gingival lesions.
Impaired Hydrogen Peroxide Detoxification -> Exogenous Hydrogen Peroxide-Triggered Blood Oxidation DIRECT Exogenous hydrogen peroxide can acutely oxidize blood when catalase-mediated clearance is deficient.
Oral Plaque Hydrogen Peroxide at Gingival Wounds -> Local Oxyhemoglobin Oxidation and Oxygen Deprivation DIRECT Patient-blood agar experiments suggest that locally generated peroxide oxidizes oxyhemoglobin and reduces oxygen availability around the lesion.
Local Oxyhemoglobin Oxidation and Oxygen Deprivation -> Necrotic Oral and Periodontal Injury INDIRECT UNKNOWN INTERMEDIATES The proposed local blood-oxidation and oxygen-deprivation sequence may help convert a gingival wound into a necrotic oral lesion.
Necrotic Oral and Periodontal Injury -> Oral ulcer DIRECT Necrotic oral injury manifests as oral ulceration.
Necrotic Oral and Periodontal Injury -> Gangrene DIRECT Progressive necrotic oral injury can manifest as gangrene.
Necrotic Oral and Periodontal Injury -> Severe periodontitis DIRECT Destructive injury of the periodontium manifests as severe or gangrenous periodontitis.
Necrotic Oral and Periodontal Injury -> Premature loss of teeth DIRECT Advanced periodontal destruction can cause early tooth loss.
Exogenous Hydrogen Peroxide-Triggered Blood Oxidation -> Methemoglobinemia DIRECT Oxidation of hemoglobin after exogenous peroxide exposure produces methemoglobinemia.
Show evidence (2 references)
PMID:120431 SUPPORT Human Clinical
"It is postulated that the gingival lesions resulted from damage to tissue from hydrogen peroxide generated by organisms in gingival plaque."
Human oral-pathology observations directly motivate the plaque hydrogen peroxide co-trigger.
PMID:39085062 SUPPORT Other
"depriving it of oxygen and causing necrosis."
The modern review summarizes the proposed local oxygen-deprivation and necrosis mechanism derived from patient-blood agar experiments.
Emerging Diabetes Susceptibility Model
emerging_diabetes_susceptibility_model EMERGING
Evidence balance 2 support
Selected human series associate inherited catalase deficiency broadly with a higher frequency of diabetes, and an alloxan-exposed acatalasemic mouse model suggests increased pancreatic beta-cell vulnerability to oxidant injury. These observations support a possible susceptibility mechanism but do not establish diabetes as an inevitable consequence of acatalasia, isolate risk in molecularly confirmed biallelic disease, or show that the experimental alloxan mechanism generalizes to unexposed humans.
Pathograph links
Biallelic CAT Pathogenic Variation -> Marked Erythrocyte Catalase Deficiency DIRECT Biallelic CAT dysfunction produces the marked erythrocyte enzyme deficiency that defines acatalasia.
Marked Erythrocyte Catalase Deficiency -> Impaired Hydrogen Peroxide Detoxification DIRECT Catalase deficiency reduces enzymatic decomposition of hydrogen peroxide.
Marked Erythrocyte Catalase Deficiency -> Reduced circulating catalase activity DIRECT Markedly reduced erythrocyte enzyme activity is the defining measurable phenotype.
Impaired Hydrogen Peroxide Detoxification -> Pancreatic Beta-Cell Oxidant Vulnerability INDIRECT UNKNOWN INTERMEDIATES Catalase deficiency may increase beta-cell vulnerability to oxidant stress, but the human causal intermediates remain uncertain.
Pancreatic Beta-Cell Oxidant Vulnerability -> Type II diabetes mellitus INDIRECT UNKNOWN INTERMEDIATES Catalase deficiency is associated with increased type 2 diabetes risk, but causal direction and generalizability remain unresolved.
Show evidence (2 references)
PMID:11117918 SUPPORT Human Clinical
"there is a higher frequency of diabetes than in unaffected first-degree relatives and the general Hungarian population."
The Hungarian series supplies cautious human association evidence.
PMID:19883754 SUPPORT Model Organism
"This study suggests that catalase plays a crucial role in the defense against oxidative-stress-mediated pancreatic beta cell death in an alloxan-induced diabetes mouse model."
The mouse experiment supports a possible beta-cell mechanism while clearly limiting it to an alloxan-induced model.
⚙

Pathophysiology

8
Biallelic CAT Pathogenic Variation
Biallelic pathogenic CAT variants reduce the amount or function of catalase, initiating the acatalasia biochemical phenotype.
Canonical CAT Deficiency and Oral Injury Model Emerging Diabetes Susceptibility Model
CAT hgnc:1516 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves CAT (hgnc:1516). hgnc:1516 is a gene from the HUGO Gene Nomenclature Committee.
catalase activity GO:0004096 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves decreased catalase activity (GO:0004096). GO:0004096 is a molecular function from the Gene Ontology. ↓ DECREASED
Downstream
Marked Erythrocyte Catalase Deficiency Biallelic CAT dysfunction produces the marked erythrocyte enzyme deficiency that defines acatalasia. Canonical CAT Deficiency and Oral Injury Model Emerging Diabetes Susceptibility Model
Show evidence (1 reference)
PMID:39079473 SUPPORT Human Clinical
"Acatalasemia is a very rare disorder characterized by gangrenous oral ulcerations and is caused by biallelic variants in the CAT gene"
The affected-family report identifies biallelic CAT variants as the cause.
Marked Erythrocyte Catalase Deficiency
Affected homozygotes have absent or very low catalase activity in blood. Heterozygous carriers have intermediate activity and are termed hypocatalasemic.
Canonical CAT Deficiency and Oral Injury Model Emerging Diabetes Susceptibility Model
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.
catalase activity GO:0004096 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves decreased catalase activity (GO:0004096). GO:0004096 is a molecular function from the Gene Ontology. ↓ DECREASED
blood UBERON:0000178 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in blood (UBERON:0000178). UBERON:0000178 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Impaired Hydrogen Peroxide Detoxification Catalase deficiency reduces enzymatic decomposition of hydrogen peroxide. Canonical CAT Deficiency and Oral Injury Model Emerging Diabetes Susceptibility Model
Reduced circulating catalase activity Markedly reduced erythrocyte enzyme activity is the defining measurable phenotype. Canonical CAT Deficiency and Oral Injury Model Emerging Diabetes Susceptibility Model
Show evidence (2 references)
PMID:24522161 SUPPORT Human Clinical
"Erythrocyte catalase activity of the patient (5.2MU/l, 4.6%)"
Quantitative human testing documents the marked erythrocyte catalase deficit.
PMID:13668563 SUPPORT Human Clinical
"Affected homozygotes have no blood catalase activity, whereas heterozygotes show activities intermediate between this inactivity and the activity of normal controls, without overlap."
Family biochemistry distinguishes affected homozygotes from heterozygous carriers.
Impaired Hydrogen Peroxide Detoxification
Reduced catalase activity impairs conversion of hydrogen peroxide to water and oxygen. Other antioxidant systems can permit clinical compensation in many individuals, but local oral or exogenous hydrogen peroxide challenges can exceed that protection.
Canonical CAT Deficiency and Oral Injury Model Emerging Diabetes Susceptibility Model
detoxification of hydrogen peroxide GO:0061691 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased detoxification of hydrogen peroxide (GO:0061691). GO:0061691 is a biological process from the Gene Ontology. ↓ DECREASED hydrogen peroxide catabolic process GO:0042744 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased hydrogen peroxide catabolic process (GO:0042744). GO:0042744 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Oral Plaque Hydrogen Peroxide at Gingival Wounds Failure to degrade microorganism-derived hydrogen peroxide permits persistence at gingival lesions. Canonical CAT Deficiency and Oral Injury Model
Exogenous Hydrogen Peroxide-Triggered Blood Oxidation Exogenous hydrogen peroxide can acutely oxidize blood when catalase-mediated clearance is deficient. Canonical CAT Deficiency and Oral Injury Model
Pancreatic Beta-Cell Oxidant Vulnerability Catalase deficiency may increase beta-cell vulnerability to oxidant stress, but the human causal intermediates remain uncertain. Emerging Diabetes Susceptibility Model
Show evidence (2 references)
PMID:39079473 SUPPORT Human Clinical
"the catalase enzyme that decomposes the hydrogen peroxide molecules to remove their toxic effect."
The disease report supports impaired hydrogen peroxide detoxification when catalase is deficient.
PMID:24025477 SUPPORT Other
"Acatalasemia means the inherited near-total deficiency of catalase activity, usually in reference to red cell catalase."
The review defines the near-total red-cell activity deficit underlying impaired peroxide handling.
Oral Plaque Hydrogen Peroxide at Gingival Wounds
Small gingival wounds provide a local niche for hydrogen peroxide-producing oral organisms. In catalase-deficient tissues and blood, this peroxide is not efficiently neutralized.
Canonical CAT Deficiency and Oral Injury Model
gingiva UBERON:0001828 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in gingiva (UBERON:0001828). UBERON:0001828 is an anatomical location from the Uberon multi-species anatomy ontology. periodontium UBERON:0001758 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in periodontium (UBERON:0001758). UBERON:0001758 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Local Oxyhemoglobin Oxidation and Oxygen Deprivation Patient-blood agar experiments suggest that locally generated peroxide oxidizes oxyhemoglobin and reduces oxygen availability around the lesion. Canonical CAT Deficiency and Oral Injury Model
Show evidence (2 references)
PMID:120431 SUPPORT Human Clinical
"It is postulated that the gingival lesions resulted from damage to tissue from hydrogen peroxide generated by organisms in gingival plaque."
The sibling report identifies plaque organisms as the local peroxide source.
PMID:39085062 SUPPORT Other
"Small wounds on the gingiva"
The review specifies the gingival wound context for the bacterial peroxide mechanism.
Local Oxyhemoglobin Oxidation and Oxygen Deprivation
Historical patient-blood agar experiments suggest that hydrogen peroxide oxidizes hemoglobin around an oral lesion. The proposed resulting loss of local oxygen delivery may promote tissue necrosis and further microbial growth; this sequence is not directly proven in vivo.
Canonical CAT Deficiency and Oral Injury Model
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.
gingiva UBERON:0001828 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in gingiva (UBERON:0001828). UBERON:0001828 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Necrotic Oral and Periodontal Injury The proposed local blood-oxidation and oxygen-deprivation sequence may help convert a gingival wound into a necrotic oral lesion. Canonical CAT Deficiency and Oral Injury Model
Show evidence (1 reference)
PMID:39085062 SUPPORT Other
"depriving it of oxygen and causing necrosis."
The review describes the proposed local oxidation, oxygen-deprivation, and necrosis sequence from patient-blood agar experiments.
Necrotic Oral and Periodontal Injury
The conditional Takahara presentation includes necrotic oral ulcers, gangrene, destructive periodontitis, alveolar bone loss, loose teeth, and premature tooth loss.
Canonical CAT Deficiency and Oral Injury Model
gingiva UBERON:0001828 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in gingiva (UBERON:0001828). UBERON:0001828 is an anatomical location from the Uberon multi-species anatomy ontology. periodontium UBERON:0001758 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in periodontium (UBERON:0001758). UBERON:0001758 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Oral ulcer Necrotic oral injury manifests as oral ulceration. Canonical CAT Deficiency and Oral Injury Model
Gangrene Progressive necrotic oral injury can manifest as gangrene. Canonical CAT Deficiency and Oral Injury Model
Severe periodontitis Destructive injury of the periodontium manifests as severe or gangrenous periodontitis. Canonical CAT Deficiency and Oral Injury Model
Premature loss of teeth Advanced periodontal destruction can cause early tooth loss. Canonical CAT Deficiency and Oral Injury Model
Show evidence (2 references)
PMID:120431 SUPPORT Human Clinical
"Gingival necrosis and severe alveolar bone destruction were the main oral manifestations."
The siblings had direct clinical evidence of necrotic gingival and alveolar injury.
PMID:39079473 SUPPORT Human Clinical
"two siblings from a consanguineous Egyptian family presenting with joint hyperlaxity, loose dentitions with gangrenous periodontitis, and early loss of teeth."
A recent affected family documents destructive periodontal disease and early tooth loss.
Exogenous Hydrogen Peroxide-Triggered Blood Oxidation
Hydrogen peroxide used for disinfection or oral procedures can overwhelm the catalase-deficient blood antioxidant system and oxidize hemoglobin. This is an exposure-conditioned complication rather than a baseline manifestation.
Canonical CAT Deficiency and Oral Injury Model
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.
blood UBERON:0000178 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in blood (UBERON:0000178). UBERON:0000178 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Methemoglobinemia Oxidation of hemoglobin after exogenous peroxide exposure produces methemoglobinemia. Canonical CAT Deficiency and Oral Injury Model
Show evidence (1 reference)
PMID:24025477 SUPPORT Other
"During anesthesia for a Japanese acatalasemic patient the disinfection with hydrogen peroxide solution caused severe methemoglobinemia."
The review summarizes an acute human exposure complication during anesthesia.
Pancreatic Beta-Cell Oxidant Vulnerability
Catalase deficiency may reduce protection of pancreatic beta cells from oxidant injury. Human evidence concerns catalase deficiency broadly rather than molecularly confirmed biallelic acatalasia and is associative and speculative; experimental support comes from an alloxan-induced mouse model rather than spontaneous human diabetes.
Emerging Diabetes Susceptibility Model
pancreatic beta cell CL:0000169 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves pancreatic beta cell, annotated with type B pancreatic cell (CL:0000169). CL:0000169 is a cell type from the Cell Ontology.
Downstream
Type II diabetes mellitus Catalase deficiency is associated with increased type 2 diabetes risk, but causal direction and generalizability remain unresolved. Emerging Diabetes Susceptibility Model
Show evidence (2 references)
PMID:11117918 SUPPORT Human Clinical
"We speculate that quantitative deficiency of catalase might predispose to cumulative oxidant damage of pancreatic beta-cells and diabetes."
The human authors explicitly present this beta-cell pathway as speculation.
PMID:19883754 SUPPORT Model Organism
"The incidence of diabetes was higher in acatalasemic mice treated with a high dose (180 mg/kg body weight) of alloxan."
The exposure model demonstrates increased diabetes susceptibility in catalase-deficient mice.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Acatalasia 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

7
Endocrine 1
Type II diabetes mellitus HP:0005978 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Type II diabetes mellitus (HP:0005978). HP:0005978 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:11117918 SUPPORT Human Clinical
"there is a higher frequency of diabetes than in unaffected first-degree relatives and the general Hungarian population."
The Hungarian series supports a population-specific association.
PMID:22365890 SUPPORT Other
"Inherited catalase deficiency may increase the risk of type 2 diabetes mellitus, especially for females."
The review appropriately frames the relationship as possible increased risk.
Head and Neck 1
Oral ulcer HP:0000155 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Oral ulcer (HP:0000155). HP:0000155 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:24522161 SUPPORT Human Clinical
"Although usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present (Takahara's disease)."
The report explicitly limits oral ulceration to a symptomatic subset.
Constitutional 1
Gangrene HP:0100758 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Gangrene (HP:0100758). HP:0100758 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:24522161 SUPPORT Human Clinical
"a syndrome of oral ulcerations and gangrene may be present (Takahara's disease)."
The report identifies gangrene as part of the symptomatic oral syndrome.
Other 4
Reduced circulating catalase activity HP:0012517 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Reduced circulating catalase activity (HP:0012517). HP:0012517 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:24522161 SUPPORT Human Clinical
"Erythrocyte catalase activity of the patient (5.2MU/l, 4.6%)"
Quantitative testing documents marked reduction in an affected patient.
PMID:13668563 SUPPORT Human Clinical
"Affected homozygotes have no blood catalase activity, whereas heterozygotes show activities intermediate between this inactivity and the activity of normal controls, without overlap."
Family testing establishes the affected and carrier biochemical ranges.
Severe periodontitis HP:0000166 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Severe periodontitis (HP:0000166). HP:0000166 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:39079473 SUPPORT Human Clinical
"loose dentitions with gangrenous periodontitis"
The affected siblings directly demonstrate destructive periodontitis.
PMID:24522161 SUPPORT Human Clinical
"Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis."
The long-term clinical report centers on severe periodontitis in acatalasia.
Premature loss of teeth HP:0006480 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Premature loss of teeth (HP:0006480). HP:0006480 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39079473 SUPPORT Human Clinical
"Premature loss of teeth is an emerging finding in our cases"
The authors explicitly scope premature tooth loss to their reported cases.
Methemoglobinemia HP:0012119 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Methemoglobinemia (HP:0012119). HP:0012119 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:24025477 SUPPORT Other
"During anesthesia for a Japanese acatalasemic patient the disinfection with hydrogen peroxide solution caused severe methemoglobinemia."
The review documents the exposure-conditioned complication.
🧬

Genetic Associations

1
CAT pathogenic variants (Causative biallelic pathogenic variants)
Gene: CAT hgnc:1516 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is CAT (hgnc:1516). hgnc:1516 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE variant_origin: GERMLINE
Autosomal recessive inheritance
Show evidence (2 references)
PMID:39079473 SUPPORT Human Clinical
"ES revealed a new homozygous missense variant in the CAT gene segregating in the family, c .635 T > G (p.Met212Arg)."
Exome sequencing identified a segregating homozygous CAT missense variant in affected siblings.
PMID:24522161 SUPPORT Human Clinical
"Direct sequencing showed a clear splicing mutation of guanine to adenine substitution at the fifth position of intron 4 in the patient."
A second human case documents a splice-region CAT disease allele.
💊

Medical Actions

4
Periodontal treatment and preventive oral care
Category: Therapeutic Action: Dental ProcedureNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Dental Procedure (NCIT:C38052). NCIT:C38052 is a clinical intervention from the NCI Thesaurus. NCIT:C38052
Individualized periodontal therapy and preventive oral care are the main case-supported management for symptomatic oral disease. A single long-term report found improved periodontal measurements and stable status after 15 years; this is not evidence for a disease-modifying cure.
Target Phenotypes: Severe periodontitis HP:0000166 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Severe periodontitis (HP:0000166). HP:0000166 is a phenotype from the Human Phenotype Ontology. Oral ulcer HP:0000155 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Oral ulcer (HP:0000155). HP:0000155 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:24522161 SUPPORT Human Clinical
"Besides, periodontal treatments and 15y follow-up were performed."
The report directly documents sustained periodontal treatment and follow-up.
PMID:24522161 SUPPORT Human Clinical
"the periodontal therapies have achieved a stable periodontal status."
The observed stable status supports case-level periodontal management.
Dental and periodontal surveillance
Category: Monitoring Action: dentist evaluationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is dentist evaluation, annotated with Dental Examination (NCIT:C158323). NCIT:C158323 is a clinical intervention from the NCI Thesaurus. Ontology label: Dental Examination NCIT:C158323
Longitudinal dental evaluation can identify and follow destructive periodontitis in patients with oral disease. No universal visit interval is inferred from the single published long-term case.
Show evidence (1 reference)
PMID:24522161 SUPPORT Human Clinical
"periodontal treatments and 15y follow-up were performed."
The case provides direct evidence for long-term periodontal follow-up without establishing a fixed schedule.
Avoidance of hydrogen peroxide exposure
Category: Counseling / Informational 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
Patients and procedural teams should avoid hydrogen peroxide-containing disinfection or oral-care exposures when alternatives are available because severe methemoglobinemia has occurred in catalase-deficient patients. The same review warns that rasburicase generates hydrogen peroxide and can produce methemoglobinemia and hemolysis in catalase deficiency.
Show evidence (2 references)
PMID:24025477 SUPPORT Other
"During anesthesia for a Japanese acatalasemic patient the disinfection with hydrogen peroxide solution caused severe methemoglobinemia."
The reported procedural complication supports an explicit peroxide-exposure precaution.
PMID:24025477 SUPPORT Other
"Patients with inherited catalase deficiency, who are treated with uric acid oxidase (rasburicase) may experience very high concentrations of hydrogen peroxide and may suffer from methemoglobinemia and hemolysis."
The review supports specific caution when a therapy generates a high hydrogen peroxide burden.
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. Ontology label: Genetic Counseling NCIT:C15240
Counseling can explain autosomal recessive recurrence and the distinction between biallelic acatalasia and heterozygous hypocatalasemia. Family enzyme testing and targeted molecular testing can identify affected relatives and carriers after a familial CAT variant is established.
Show evidence (2 references)
PMID:13668563 SUPPORT Human Clinical
"The heterozygous carrier state of a rare hereditary disease, acatalasemia, has been defined biochemically."
Family biochemistry demonstrates that the heterozygous carrier state can be identified.
PMID:120431 SUPPORT Human Clinical
"Thirteen hypocatalasemic individuals, including both parents, were found among 29 relatives of the probands examined from four generations."
Multigeneration family evaluation detected numerous hypocatalasemic carriers.
🔬

Biochemical Markers

1
Reduced erythrocyte catalase activity (DECREASED)
Context: Quantitative blood catalase activity is markedly reduced in affected homozygotes and intermediate in heterozygous carriers. It is a defining diagnostic readout rather than evidence of generalized peroxisome failure.
Pathograph Readouts
Readout Of Marked Erythrocyte Catalase Deficiency Negative Diagnostic
Lower erythrocyte catalase activity directly reports the defining enzyme-deficiency node.
Show evidence (1 reference)
PMID:24522161 SUPPORT Human Clinical
"Erythrocyte catalase activity was measured by ultraviolet spectrophotometer."
The patient report identifies the quantitative erythrocyte assay used for diagnosis.
Show evidence (2 references)
PMID:24522161 SUPPORT Human Clinical
"Erythrocyte catalase activity of the patient (5.2MU/l, 4.6%)"
The assay result demonstrates marked activity reduction.
PMID:13668563 SUPPORT Human Clinical
"heterozygotes show activities intermediate between this inactivity and the activity of normal controls, without overlap."
Carrier-state data support the discriminatory biochemical range.
🔬

Diagnosis

2
Quantitative erythrocyte catalase activity assessment
Quantitative erythrocyte catalase activity is the defining biochemical assay. Marked or near-total deficiency supports acatalasia, while intermediate activity can suggest heterozygous hypocatalasemia; testing for a familial CAT variant is preferred for carrier confirmation. Oral findings alone are neither necessary nor sufficient because most affected people are asymptomatic.
erythrocyte enzyme activity assessment NCIT:C25294 NCI Thesaurus (NCIT)
Results: Markedly reduced erythrocyte catalase activity supports acatalasia; intermediate activity suggests carrier status and should be confirmed molecularly when a familial variant is known.
Show evidence (2 references)
PMID:24522161 SUPPORT Human Clinical
"Erythrocyte catalase activity was measured by ultraviolet spectrophotometer."
The human report describes quantitative erythrocyte catalase measurement for diagnostic confirmation.
PMID:13668563 SUPPORT Human Clinical
"Affected homozygotes have no blood catalase activity, whereas heterozygotes show activities intermediate between this inactivity and the activity of normal controls, without overlap."
This historical family study supports a biochemical distinction among affected, carrier, and normal ranges without establishing universal modern cutoffs.
CAT molecular genetic testing
Sequencing CAT confirms the molecular diagnosis when biallelic pathogenic variants are identified and enables family-specific testing. Molecular confirmation is especially useful when oral phenotypes overlap other inherited periodontal disorders.
molecular genetic testing NCIT:C19770 NCI Thesaurus (NCIT)
Results: Biallelic pathogenic CAT variants confirm CAT-related acatalasia in the appropriate biochemical context.
Show evidence (2 references)
PMID:24522161 SUPPORT Human Clinical
"To confirm the diagnosis of acatalasemia, intron 4 of the catalase gene was amplified and sequenced."
The report explicitly used CAT sequencing for diagnostic confirmation.
PMID:39079473 SUPPORT Human Clinical
"ES revealed a new homozygous missense variant in the CAT gene segregating in the family, c .635 T > G (p.Met212Arg)."
Exome sequencing established the molecular diagnosis in affected siblings with a periodontal phenocopy.
📈

Progression

3
Lifelong biochemical state
Age: Birth onward
Marked erythrocyte catalase deficiency is lifelong, but most affected individuals remain clinically asymptomatic and may be recognized through family investigation or biochemical testing rather than symptoms.
Show evidence (2 references)
PMID:24522161 SUPPORT Human Clinical
"Although usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present (Takahara's disease)."
The report distinguishes the usually asymptomatic biochemical disorder from its oral symptomatic presentation.
PMID:13668563 SUPPORT Human Clinical
"Affected homozygotes have no blood catalase activity, whereas heterozygotes show activities intermediate between this inactivity and the activity of normal controls, without overlap."
Biochemical family data establish the marked lifelong activity difference in affected homozygotes and carriers.
Oral Takahara presentation
Age: Variable; classic reports include childhood
In a symptomatic subset, gingival injury can progress to necrotic ulcers, oral gangrene, severe periodontal and alveolar destruction, tooth mobility, and premature tooth loss. Childhood cases are well documented, but childhood onset is not asserted as universal.
Show evidence (2 references)
PMID:120431 SUPPORT Human Clinical
"The oral findings in two Peruvian brothers, 10- and 11-years-old, with acatalasia are presented. Gingival necrosis and severe alveolar bone destruction were the main oral manifestations."
The sibling report documents a childhood oral-disease presentation with necrosis and alveolar destruction.
PMID:39085062 SUPPORT Other
"symptomatic acatalasemia has decreased"
The review supports a treatment- and environment-modified decline in the symptomatic oral presentation.
Treatment-modified periodontal course
Age: Long-term follow-up
Disease-specific management evidence is limited to case-level experience. In one patient, sustained periodontal therapy over 15 years was associated with improved periodontal measurements and stable periodontal status.
Show evidence (2 references)
PMID:24522161 SUPPORT Human Clinical
"After 15-y treatments, the periodontal pocket depth ≥4mm and clinical attachment loss reduced to 30% and 3.7±1.2mm."
The long-term case documents improvement in periodontal measures during treatment.
PMID:24522161 SUPPORT Human Clinical
"the periodontal therapies have achieved a stable periodontal status."
The report concludes that long-term periodontal therapy achieved clinical stability.
📊

Prevalence

1
Japan
Unknown 0.416667 per 100,000 1–9 per 1,000,000
A 2024 historical and genetic review reports a Japanese frequency of 1 in 240,000. The source calls this a frequency without specifying a point, birth, or period-prevalence denominator, so the measure type remains explicitly unknown.
Show evidence (1 reference)
PMID:39085062 SUPPORT Other
"acatalasemia in Japan is low (1/240,000)"
The contemporary review reports the Japanese population frequency used for this estimate.
🔀

Differential Diagnoses

1

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

Ehlers-Danlos syndrome, periodontitis type Not Yet Curated MONDO:0007527
Overlapping Features Periodontal Ehlers-Danlos syndrome can present with early destructive periodontitis, tooth mobility or loss, and connective-tissue findings. A recent acatalasia family was initially investigated for this condition because of joint hyperlaxity and gangrenous periodontitis.
Distinguishing Features
  • Markedly reduced erythrocyte catalase activity and biallelic CAT variants favor acatalasia.
  • A pathogenic C1R or C1S finding with the periodontal Ehlers-Danlos phenotype favors periodontal Ehlers-Danlos syndrome.
Show evidence (2 references)
PMID:39079473 SUPPORT Human Clinical
"The patients were clinically suspected to have the periodontal type of Ehlers-Danlos syndrome and thus genetic testing of C1S and C1R causative genes was carried out first"
The affected family directly demonstrates the periodontal Ehlers-Danlos clinical differential.
PMID:39079473 SUPPORT Human Clinical
"No pathogenic variants were detected in C1S and C1R genes then ES revealed a new homozygous missense variant in the CAT gene segregating in the family"
Molecular testing resolved the phenocopy in favor of CAT-related acatalasia.
{ }

Source YAML

click to show 
name: Acatalasia
creation_date: "2026-07-06T06:09:44Z"
category: Mendelian
description: >-
  Acatalasia (acatalasemia) is a rare autosomal recessive inborn error caused
  by biallelic CAT pathogenic variants and defined biochemically by marked,
  often near-total deficiency of catalase activity in erythrocytes. Most
  affected people are clinically asymptomatic. In the symptomatic oral
  presentation historically called Takahara disease, hydrogen peroxide
  produced by oral microorganisms at gingival wounds is not efficiently
  detoxified. A proposed local blood-oxidation and oxygen-deprivation mechanism
  may then promote necrotic ulceration, gangrene, severe periodontitis, and tooth
  loss. Exogenous hydrogen
  peroxide is an important methemoglobinemia hazard. An association with type 2
  diabetes has been reported in selected populations, but its generalizability
  and causal mechanism remain uncertain.
disease_term:
  preferred_term: acatalasia
  term:
    id: MONDO:0013571
    label: acatalasia
synonyms:
- Acatalasemia
- Catalase deficiency
- CAT-related acatalasemia
parents:
- Inborn Error of Metabolism
notes: >-
  OMIM:614097; ORPHA:926. Takahara disease is used here for the symptomatic
  oral-ulceration and gangrene presentation, not as an unconditional synonym
  for every person with acatalasia. Heterozygous partial catalase deficiency is
  termed hypocatalasemia and represents the carrier state rather than the
  biallelic disease modeled in this entry.
classifications:
  harrisons_chapter:
  - classification_value: GENETICS_ENVIRONMENT_DISEASE
    evidence:
    - reference: PMID:24522161
      reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Acatalasemia is a rare genetic catalase deficiency that is inherited as an autosomal recessive trait."
      explanation: The clinical report supports classification as a Mendelian genetic disorder.
  icimd_category:
  - classification_value: intermediary_metabolism_miscellaneous
    notes: >-
      ICIMD category 13.2, other miscellaneous or unassigned disorders of
      intermediary metabolism. Acatalasia is an inherited enzyme-activity
      deficiency affecting hydrogen peroxide metabolism.
    evidence:
    - reference: PMID:24025477
      reference_title: "Inherited catalase deficiency: is it benign or a factor in various age related disorders?"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Acatalasemia means the inherited near-total deficiency of catalase activity, usually in reference to red cell catalase."
      explanation: >-
        The review supports the inherited metabolic enzyme-deficiency basis for
        the retained ICIMD placement; the specific miscellaneous category is a
        curator-applied nosology assignment.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0013571
      label: acatalasia
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: MONDO:0013571 is the canonical acatalasia concept used by this entry.
inheritance:
- name: Autosomal recessive inheritance
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Acatalasemia is a rare genetic catalase deficiency that is inherited as an autosomal recessive trait."
    explanation: The report explicitly states the autosomal recessive inheritance pattern.
  - reference: PMID:120431
    reference_title: Acatalasia in two Peruvian siblings.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The inheritance pattern in the kindred was compatible with an autosomal recessive disorder."
    explanation: The multigeneration pedigree independently supports recessive inheritance.
prevalence:
- population: Japan
  measure_type: UNKNOWN
  prevalence_class: BAND_1_9_PER_1000000
  rate_per_100000: 0.416667
  notes: >-
    A 2024 historical and genetic review reports a Japanese frequency of 1 in
    240,000. The source calls this a frequency without specifying a point,
    birth, or period-prevalence denominator, so the measure type remains
    explicitly unknown.
  evidence:
  - reference: PMID:39085062
    reference_title: The discovery of acatalasemia (lack of catalase in the blood) and its significance in human genetics.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "acatalasemia in Japan is low (1/240,000)"
    explanation: The contemporary review reports the Japanese population frequency used for this estimate.
progression:
- phase: Lifelong biochemical state
  age_range: Birth onward
  notes: >-
    Marked erythrocyte catalase deficiency is lifelong, but most affected
    individuals remain clinically asymptomatic and may be recognized through
    family investigation or biochemical testing rather than symptoms.
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Although usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present (Takahara's disease)."
    explanation: The report distinguishes the usually asymptomatic biochemical disorder from its oral symptomatic presentation.
  - reference: PMID:13668563
    reference_title: Carrier state in human acatalasemia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Affected homozygotes have no blood catalase activity, whereas heterozygotes show activities intermediate between this inactivity and the activity of normal controls, without overlap."
    explanation: Biochemical family data establish the marked lifelong activity difference in affected homozygotes and carriers.
- phase: Oral Takahara presentation
  age_range: Variable; classic reports include childhood
  notes: >-
    In a symptomatic subset, gingival injury can progress to necrotic ulcers,
    oral gangrene, severe periodontal and alveolar destruction, tooth mobility,
    and premature tooth loss. Childhood cases are well documented, but
    childhood onset is not asserted as universal.
  evidence:
  - reference: PMID:120431
    reference_title: Acatalasia in two Peruvian siblings.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The oral findings in two Peruvian brothers, 10- and 11-years-old, with acatalasia are presented. Gingival necrosis and severe alveolar bone destruction were the main oral manifestations."
    explanation: The sibling report documents a childhood oral-disease presentation with necrosis and alveolar destruction.
  - reference: PMID:39085062
    reference_title: The discovery of acatalasemia (lack of catalase in the blood) and its significance in human genetics.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "symptomatic acatalasemia has decreased"
    explanation: The review supports a treatment- and environment-modified decline in the symptomatic oral presentation.
- phase: Treatment-modified periodontal course
  age_range: Long-term follow-up
  notes: >-
    Disease-specific management evidence is limited to case-level experience.
    In one patient, sustained periodontal therapy over 15 years was associated
    with improved periodontal measurements and stable periodontal status.
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "After 15-y treatments, the periodontal pocket depth ≥4mm and clinical attachment loss reduced to 30% and 3.7±1.2mm."
    explanation: The long-term case documents improvement in periodontal measures during treatment.
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the periodontal therapies have achieved a stable periodontal status."
    explanation: The report concludes that long-term periodontal therapy achieved clinical stability.
mechanistic_hypotheses:
- hypothesis_group_id: canonical_cat_deficiency_oral_injury_model
  hypothesis_label: Canonical CAT Deficiency and Oral Injury Model
  status: CANONICAL
  description: >-
    Biallelic CAT variants produce marked erythrocyte catalase deficiency and
    impaired hydrogen peroxide decomposition. Most affected people remain
    asymptomatic, but at gingival wounds hydrogen peroxide-producing oral
    microorganisms can create a local oxidant burden. Historical patient-blood
    agar experiments propose that oxyhemoglobin oxidation, reduced oxygen
    availability, and a self-reinforcing necrotic ulcer and periodontal-injury
    cycle follow. The same
    catalase deficit makes exogenous hydrogen peroxide an acute
    methemoglobinemia hazard.
  notes: >-
    The oral co-trigger is conditional rather than inevitable. The graph does
    not treat acatalasia as a generalized peroxisome-biogenesis disorder and
    does not infer chronic hemolysis or universal systemic oxidative injury.
  evidence:
  - reference: PMID:120431
    reference_title: Acatalasia in two Peruvian siblings.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It is postulated that the gingival lesions resulted from damage to tissue from hydrogen peroxide generated by organisms in gingival plaque."
    explanation: Human oral-pathology observations directly motivate the plaque hydrogen peroxide co-trigger.
  - reference: PMID:39085062
    reference_title: The discovery of acatalasemia (lack of catalase in the blood) and its significance in human genetics.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "depriving it of oxygen and causing necrosis."
    explanation: The modern review summarizes the proposed local oxygen-deprivation and necrosis mechanism derived from patient-blood agar experiments.
- hypothesis_group_id: emerging_diabetes_susceptibility_model
  hypothesis_label: Emerging Diabetes Susceptibility Model
  status: EMERGING
  description: >-
    Selected human series associate inherited catalase deficiency broadly with a higher
    frequency of diabetes, and an alloxan-exposed acatalasemic mouse model
    suggests increased pancreatic beta-cell vulnerability to oxidant injury.
    These observations support a possible susceptibility mechanism but do not
    establish diabetes as an inevitable consequence of acatalasia, isolate risk
    in molecularly confirmed biallelic disease, or show that the experimental
    alloxan mechanism generalizes to unexposed humans.
  evidence:
  - reference: PMID:11117918
    reference_title: Hereditary catalase deficiencies and increased risk of diabetes.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "there is a higher frequency of diabetes than in unaffected first-degree relatives and the general Hungarian population."
    explanation: The Hungarian series supplies cautious human association evidence.
  - reference: PMID:19883754
    reference_title: Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "This study suggests that catalase plays a crucial role in the defense against oxidative-stress-mediated pancreatic beta cell death in an alloxan-induced diabetes mouse model."
    explanation: The mouse experiment supports a possible beta-cell mechanism while clearly limiting it to an alloxan-induced model.
pathophysiology:
- name: Biallelic CAT Pathogenic Variation
  description: >-
    Biallelic pathogenic CAT variants reduce the amount or function of catalase,
    initiating the acatalasia biochemical phenotype.
  role: trigger
  gene:
    preferred_term: CAT
    term:
      id: hgnc:1516
      label: CAT
  molecular_functions:
  - preferred_term: catalase activity
    term:
      id: GO:0004096
      label: catalase activity
    modifier: DECREASED
  evidence:
  - reference: PMID:39079473
    reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Acatalasemia is a very rare disorder characterized by gangrenous oral ulcerations and is caused by biallelic variants in the CAT gene"
    explanation: The affected-family report identifies biallelic CAT variants as the cause.
  downstream:
  - target: Marked Erythrocyte Catalase Deficiency
    causal_link_type: DIRECT
    description: Biallelic CAT dysfunction produces the marked erythrocyte enzyme deficiency that defines acatalasia.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    - emerging_diabetes_susceptibility_model
    evidence:
    - reference: PMID:24522161
      reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Direct sequencing showed a clear splicing mutation of guanine to adenine substitution at the fifth position of intron 4 in the patient. Erythrocyte catalase activity of the patient (5.2MU/l, 4.6%)"
      explanation: Molecular and erythrocyte-enzyme findings in the same patient directly link a CAT splice variant to marked catalase deficiency.
- name: Marked Erythrocyte Catalase Deficiency
  description: >-
    Affected homozygotes have absent or very low catalase activity in blood.
    Heterozygous carriers have intermediate activity and are termed
    hypocatalasemic.
  role: mediator
  cell_types:
  - preferred_term: erythrocyte
    term:
      id: CL:0000232
      label: erythrocyte
  locations:
  - preferred_term: blood
    term:
      id: UBERON:0000178
      label: blood
  molecular_functions:
  - preferred_term: catalase activity
    term:
      id: GO:0004096
      label: catalase activity
    modifier: DECREASED
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Erythrocyte catalase activity of the patient (5.2MU/l, 4.6%)"
    explanation: Quantitative human testing documents the marked erythrocyte catalase deficit.
  - reference: PMID:13668563
    reference_title: Carrier state in human acatalasemia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Affected homozygotes have no blood catalase activity, whereas heterozygotes show activities intermediate between this inactivity and the activity of normal controls, without overlap."
    explanation: Family biochemistry distinguishes affected homozygotes from heterozygous carriers.
  downstream:
  - target: Impaired Hydrogen Peroxide Detoxification
    causal_link_type: DIRECT
    description: Catalase deficiency reduces enzymatic decomposition of hydrogen peroxide.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    - emerging_diabetes_susceptibility_model
    evidence:
    - reference: PMID:39079473
      reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "the CAT gene which encodes the catalase enzyme that decomposes the hydrogen peroxide molecules to remove their toxic effect."
      explanation: The human report states the hydrogen peroxide-decomposition function lost in CAT-related acatalasia.
  - target: Reduced circulating catalase activity
    causal_link_type: DIRECT
    description: Markedly reduced erythrocyte enzyme activity is the defining measurable phenotype.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    - emerging_diabetes_susceptibility_model
    evidence:
    - reference: PMID:24522161
      reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Erythrocyte catalase activity of the patient (5.2MU/l, 4.6%)"
      explanation: The quantitative erythrocyte assay directly supports the reduced-catalase phenotype.
- name: Impaired Hydrogen Peroxide Detoxification
  description: >-
    Reduced catalase activity impairs conversion of hydrogen peroxide to water
    and oxygen. Other antioxidant systems can permit clinical compensation in
    many individuals, but local oral or exogenous hydrogen peroxide challenges
    can exceed that protection.
  role: mediator
  biological_processes:
  - preferred_term: detoxification of hydrogen peroxide
    term:
      id: GO:0061691
      label: detoxification of hydrogen peroxide
    modifier: DECREASED
  - preferred_term: hydrogen peroxide catabolic process
    term:
      id: GO:0042744
      label: hydrogen peroxide catabolic process
    modifier: DECREASED
  evidence:
  - reference: PMID:39079473
    reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the catalase enzyme that decomposes the hydrogen peroxide molecules to remove their toxic effect."
    explanation: The disease report supports impaired hydrogen peroxide detoxification when catalase is deficient.
  - reference: PMID:24025477
    reference_title: "Inherited catalase deficiency: is it benign or a factor in various age related disorders?"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Acatalasemia means the inherited near-total deficiency of catalase activity, usually in reference to red cell catalase."
    explanation: The review defines the near-total red-cell activity deficit underlying impaired peroxide handling.
  downstream:
  - target: Oral Plaque Hydrogen Peroxide at Gingival Wounds
    causal_link_type: DIRECT
    description: Failure to degrade microorganism-derived hydrogen peroxide permits persistence at gingival lesions.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    evidence:
    - reference: PMID:120431
      reference_title: Acatalasia in two Peruvian siblings.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The hydrogen peroxide cannot be degraded by gingival tissue or by leukocytes genetically lacking the enzyme catalase."
      explanation: The human oral-pathology report directly links catalase deficiency to failed local peroxide degradation.
  - target: Exogenous Hydrogen Peroxide-Triggered Blood Oxidation
    causal_link_type: DIRECT
    description: Exogenous hydrogen peroxide can acutely oxidize blood when catalase-mediated clearance is deficient.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    evidence:
    - reference: PMID:24025477
      reference_title: "Inherited catalase deficiency: is it benign or a factor in various age related disorders?"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "During anesthesia for a Japanese acatalasemic patient the disinfection with hydrogen peroxide solution caused severe methemoglobinemia."
      explanation: The clinical hazard summarized by the review directly connects hydrogen peroxide exposure to blood oxidation in acatalasia.
  - target: Pancreatic Beta-Cell Oxidant Vulnerability
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Catalase deficiency may increase beta-cell vulnerability to oxidant stress, but the human causal intermediates remain uncertain.
    hypothesis_groups:
    - emerging_diabetes_susceptibility_model
    evidence:
    - reference: PMID:11117918
      reference_title: Hereditary catalase deficiencies and increased risk of diabetes.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "We speculate that quantitative deficiency of catalase might predispose to cumulative oxidant damage of pancreatic beta-cells and diabetes."
      explanation: The human paper explicitly labels the beta-cell pathway as a speculation rather than an established mechanism.
    - reference: PMID:19883754
      reference_title: Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "A higher dose of alloxan accelerated severe atrophy of pancreatic islets and induced pancreatic beta cell apoptosis in acatalasemic mice in comparison to wild-type mice."
      explanation: The alloxan-exposed mouse model supplies experimental evidence for increased beta-cell vulnerability.
- name: Oral Plaque Hydrogen Peroxide at Gingival Wounds
  description: >-
    Small gingival wounds provide a local niche for hydrogen peroxide-producing
    oral organisms. In catalase-deficient tissues and blood, this peroxide is
    not efficiently neutralized.
  role: mediator
  locations:
  - preferred_term: gingiva
    term:
      id: UBERON:0001828
      label: gingiva
  - preferred_term: periodontium
    term:
      id: UBERON:0001758
      label: periodontium
  chemical_entities:
  - preferred_term: hydrogen peroxide
    term:
      id: CHEBI:16240
      label: hydrogen peroxide
    modifier: INCREASED
  evidence:
  - reference: PMID:120431
    reference_title: Acatalasia in two Peruvian siblings.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It is postulated that the gingival lesions resulted from damage to tissue from hydrogen peroxide generated by organisms in gingival plaque."
    explanation: The sibling report identifies plaque organisms as the local peroxide source.
  - reference: PMID:39085062
    reference_title: The discovery of acatalasemia (lack of catalase in the blood) and its significance in human genetics.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Small wounds on the gingiva"
    explanation: The review specifies the gingival wound context for the bacterial peroxide mechanism.
  downstream:
  - target: Local Oxyhemoglobin Oxidation and Oxygen Deprivation
    causal_link_type: DIRECT
    description: Patient-blood agar experiments suggest that locally generated peroxide oxidizes oxyhemoglobin and reduces oxygen availability around the lesion.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    evidence:
    - reference: PMID:39085062
      reference_title: The discovery of acatalasemia (lack of catalase in the blood) and its significance in human genetics.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "likely oxidized the oxyhemoglobin"
      explanation: Patient-blood agar experiments support this proposed peroxide-mediated oxyhemoglobin oxidation step ex vivo.
- name: Local Oxyhemoglobin Oxidation and Oxygen Deprivation
  description: >-
    Historical patient-blood agar experiments suggest that hydrogen peroxide
    oxidizes hemoglobin around an oral lesion. The proposed resulting loss of
    local oxygen delivery may promote tissue necrosis and further microbial
    growth; this sequence is not directly proven in vivo.
  role: mediator
  cell_types:
  - preferred_term: erythrocyte
    term:
      id: CL:0000232
      label: erythrocyte
  locations:
  - preferred_term: gingiva
    term:
      id: UBERON:0001828
      label: gingiva
  evidence:
  - reference: PMID:39085062
    reference_title: The discovery of acatalasemia (lack of catalase in the blood) and its significance in human genetics.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "depriving it of oxygen and causing necrosis."
    explanation: The review describes the proposed local oxidation, oxygen-deprivation, and necrosis sequence from patient-blood agar experiments.
  downstream:
  - target: Necrotic Oral and Periodontal Injury
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: The proposed local blood-oxidation and oxygen-deprivation sequence may help convert a gingival wound into a necrotic oral lesion.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    evidence:
    - reference: PMID:39085062
      reference_title: The discovery of acatalasemia (lack of catalase in the blood) and its significance in human genetics.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "This process can transform a small wound into a deep ulcer characterized by prominent necrosis"
      explanation: The review proposes that the local oxidation cycle can transform a small wound into a deep necrotic ulcer.
- name: Necrotic Oral and Periodontal Injury
  description: >-
    The conditional Takahara presentation includes necrotic oral ulcers,
    gangrene, destructive periodontitis, alveolar bone loss, loose teeth, and
    premature tooth loss.
  role: consequence
  locations:
  - preferred_term: gingiva
    term:
      id: UBERON:0001828
      label: gingiva
  - preferred_term: periodontium
    term:
      id: UBERON:0001758
      label: periodontium
  evidence:
  - reference: PMID:120431
    reference_title: Acatalasia in two Peruvian siblings.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Gingival necrosis and severe alveolar bone destruction were the main oral manifestations."
    explanation: The siblings had direct clinical evidence of necrotic gingival and alveolar injury.
  - reference: PMID:39079473
    reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "two siblings from a consanguineous Egyptian family presenting with joint hyperlaxity, loose dentitions with gangrenous periodontitis, and early loss of teeth."
    explanation: A recent affected family documents destructive periodontal disease and early tooth loss.
  downstream:
  - target: Oral ulcer
    causal_link_type: DIRECT
    description: Necrotic oral injury manifests as oral ulceration.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    evidence:
    - reference: PMID:24522161
      reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "a syndrome of oral ulcerations and gangrene may be present (Takahara's disease)."
      explanation: The clinical report identifies oral ulceration as part of Takahara disease.
  - target: Gangrene
    causal_link_type: DIRECT
    description: Progressive necrotic oral injury can manifest as gangrene.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    evidence:
    - reference: PMID:24522161
      reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "a syndrome of oral ulcerations and gangrene may be present (Takahara's disease)."
      explanation: The report identifies gangrene as the defining symptomatic oral presentation.
  - target: Severe periodontitis
    causal_link_type: DIRECT
    description: Destructive injury of the periodontium manifests as severe or gangrenous periodontitis.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    evidence:
    - reference: PMID:39079473
      reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "loose dentitions with gangrenous periodontitis"
      explanation: The affected siblings directly demonstrate severe gangrenous periodontitis.
  - target: Premature loss of teeth
    causal_link_type: DIRECT
    description: Advanced periodontal destruction can cause early tooth loss.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    evidence:
    - reference: PMID:39079473
      reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Premature loss of teeth is an emerging finding in our cases"
      explanation: The recent family report explicitly records premature tooth loss as an emerging case feature.
- name: Exogenous Hydrogen Peroxide-Triggered Blood Oxidation
  description: >-
    Hydrogen peroxide used for disinfection or oral procedures can overwhelm
    the catalase-deficient blood antioxidant system and oxidize hemoglobin.
    This is an exposure-conditioned complication rather than a baseline
    manifestation.
  role: consequence
  cell_types:
  - preferred_term: erythrocyte
    term:
      id: CL:0000232
      label: erythrocyte
  locations:
  - preferred_term: blood
    term:
      id: UBERON:0000178
      label: blood
  chemical_entities:
  - preferred_term: hydrogen peroxide
    term:
      id: CHEBI:16240
      label: hydrogen peroxide
    modifier: INCREASED
  evidence:
  - reference: PMID:24025477
    reference_title: "Inherited catalase deficiency: is it benign or a factor in various age related disorders?"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "During anesthesia for a Japanese acatalasemic patient the disinfection with hydrogen peroxide solution caused severe methemoglobinemia."
    explanation: The review summarizes an acute human exposure complication during anesthesia.
  downstream:
  - target: Methemoglobinemia
    causal_link_type: DIRECT
    description: Oxidation of hemoglobin after exogenous peroxide exposure produces methemoglobinemia.
    hypothesis_groups:
    - canonical_cat_deficiency_oral_injury_model
    evidence:
    - reference: PMID:24025477
      reference_title: "Inherited catalase deficiency: is it benign or a factor in various age related disorders?"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Hydrogen peroxide may cause methemoglobinemia in patients with catalase deficiency."
      explanation: The review directly states the exposure-conditioned methemoglobinemia relationship.
- name: Pancreatic Beta-Cell Oxidant Vulnerability
  description: >-
    Catalase deficiency may reduce protection of pancreatic beta cells from
    oxidant injury. Human evidence concerns catalase deficiency broadly rather
    than molecularly confirmed biallelic acatalasia and is associative and
    speculative; experimental support comes from an alloxan-induced mouse model
    rather than spontaneous human diabetes.
  role: consequence
  mechanism_confidence: PROVISIONAL
  cell_types:
  - preferred_term: pancreatic beta cell
    term:
      id: CL:0000169
      label: type B pancreatic cell
  evidence:
  - reference: PMID:11117918
    reference_title: Hereditary catalase deficiencies and increased risk of diabetes.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We speculate that quantitative deficiency of catalase might predispose to cumulative oxidant damage of pancreatic beta-cells and diabetes."
    explanation: The human authors explicitly present this beta-cell pathway as speculation.
  - reference: PMID:19883754
    reference_title: Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "The incidence of diabetes was higher in acatalasemic mice treated with a high dose (180 mg/kg body weight) of alloxan."
    explanation: The exposure model demonstrates increased diabetes susceptibility in catalase-deficient mice.
  downstream:
  - target: Type II diabetes mellitus
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Catalase deficiency is associated with increased type 2 diabetes risk, but causal direction and generalizability remain unresolved.
    hypothesis_groups:
    - emerging_diabetes_susceptibility_model
    evidence:
    - reference: PMID:11117918
      reference_title: Hereditary catalase deficiencies and increased risk of diabetes.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "there is a higher frequency of diabetes than in unaffected first-degree relatives and the general Hungarian population."
      explanation: The selected Hungarian series supports an association, not deterministic causation.
    - reference: PMID:22365890
      reference_title: Acatalasemia and diabetes mellitus.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Inherited catalase deficiency may increase the risk of type 2 diabetes mellitus, especially for females."
      explanation: The review explicitly calibrates the finding as possible increased risk.
phenotypes:
- name: Reduced circulating catalase activity
  category: Biochemical
  description: >-
    Markedly reduced erythrocyte catalase activity is the defining biochemical
    finding; heterozygous carriers have intermediate activity.
  phenotype_term:
    preferred_term: Reduced circulating catalase activity
    term:
      id: HP:0012517
      label: Reduced circulating catalase activity
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Erythrocyte catalase activity of the patient (5.2MU/l, 4.6%)"
    explanation: Quantitative testing documents marked reduction in an affected patient.
  - reference: PMID:13668563
    reference_title: Carrier state in human acatalasemia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Affected homozygotes have no blood catalase activity, whereas heterozygotes show activities intermediate between this inactivity and the activity of normal controls, without overlap."
    explanation: Family testing establishes the affected and carrier biochemical ranges.
- name: Oral ulcer
  category: Oral
  description: >-
    Oral ulceration occurs in the symptomatic Takahara presentation but is not
    required for diagnosis because most affected people are asymptomatic.
  phenotype_term:
    preferred_term: Oral ulcer
    term:
      id: HP:0000155
      label: Oral ulcer
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Although usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present (Takahara's disease)."
    explanation: The report explicitly limits oral ulceration to a symptomatic subset.
- name: Gangrene
  category: Oral
  description: >-
    Progressive necrotic oral disease can produce gangrene in the Takahara
    presentation.
  phenotype_term:
    preferred_term: Gangrene
    term:
      id: HP:0100758
      label: Gangrene
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a syndrome of oral ulcerations and gangrene may be present (Takahara's disease)."
    explanation: The report identifies gangrene as part of the symptomatic oral syndrome.
- name: Severe periodontitis
  category: Oral
  description: Severe or gangrenous periodontitis is documented in symptomatic cases.
  phenotype_term:
    preferred_term: Severe periodontitis
    term:
      id: HP:0000166
      label: Severe periodontitis
  evidence:
  - reference: PMID:39079473
    reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "loose dentitions with gangrenous periodontitis"
    explanation: The affected siblings directly demonstrate destructive periodontitis.
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis."
    explanation: The long-term clinical report centers on severe periodontitis in acatalasia.
- name: Premature loss of teeth
  category: Oral
  description: >-
    Premature tooth loss has been reported with gangrenous periodontitis in a
    recent affected family and should not be interpreted as a population
    frequency estimate.
  phenotype_term:
    preferred_term: Premature loss of teeth
    term:
      id: HP:0006480
      label: Premature loss of teeth
  evidence:
  - reference: PMID:39079473
    reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Premature loss of teeth is an emerging finding in our cases"
    explanation: The authors explicitly scope premature tooth loss to their reported cases.
- name: Methemoglobinemia
  category: Exposure-conditioned complication
  description: >-
    Methemoglobinemia can occur after exogenous hydrogen peroxide exposure,
    including hydrogen peroxide disinfection during anesthesia; it is not
    modeled as a baseline manifestation.
  phenotype_term:
    preferred_term: Methemoglobinemia
    term:
      id: HP:0012119
      label: Methemoglobinemia
  evidence:
  - reference: PMID:24025477
    reference_title: "Inherited catalase deficiency: is it benign or a factor in various age related disorders?"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "During anesthesia for a Japanese acatalasemic patient the disinfection with hydrogen peroxide solution caused severe methemoglobinemia."
    explanation: The review documents the exposure-conditioned complication.
- name: Type II diabetes mellitus
  category: Associated susceptibility
  description: >-
    Increased type 2 diabetes risk has been reported in selected
    catalase-deficient populations without isolating molecularly confirmed
    biallelic acatalasia. This association is not a defining phenotype, may not
    generalize across populations, and does not establish direct causation.
  phenotype_term:
    preferred_term: Type II diabetes mellitus
    term:
      id: HP:0005978
      label: Type II diabetes mellitus
  evidence:
  - reference: PMID:11117918
    reference_title: Hereditary catalase deficiencies and increased risk of diabetes.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "there is a higher frequency of diabetes than in unaffected first-degree relatives and the general Hungarian population."
    explanation: The Hungarian series supports a population-specific association.
  - reference: PMID:22365890
    reference_title: Acatalasemia and diabetes mellitus.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Inherited catalase deficiency may increase the risk of type 2 diabetes mellitus, especially for females."
    explanation: The review appropriately frames the relationship as possible increased risk.
biochemical:
- name: Reduced erythrocyte catalase activity
  presence: DECREASED
  context: >-
    Quantitative blood catalase activity is markedly reduced in affected
    homozygotes and intermediate in heterozygous carriers. It is a defining
    diagnostic readout rather than evidence of generalized peroxisome failure.
  readouts:
  - target: Marked Erythrocyte Catalase Deficiency
    relationship: READOUT_OF
    direction: NEGATIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Lower erythrocyte catalase activity directly reports the defining enzyme-deficiency node.
    evidence:
    - reference: PMID:24522161
      reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Erythrocyte catalase activity was measured by ultraviolet spectrophotometer."
      explanation: The patient report identifies the quantitative erythrocyte assay used for diagnosis.
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Erythrocyte catalase activity of the patient (5.2MU/l, 4.6%)"
    explanation: The assay result demonstrates marked activity reduction.
  - reference: PMID:13668563
    reference_title: Carrier state in human acatalasemia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "heterozygotes show activities intermediate between this inactivity and the activity of normal controls, without overlap."
    explanation: Carrier-state data support the discriminatory biochemical range.
genetic:
- name: CAT pathogenic variants
  gene_term:
    preferred_term: CAT
    term:
      id: hgnc:1516
      label: CAT
  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:24522161
      reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Acatalasemia is a rare genetic catalase deficiency that is inherited as an autosomal recessive trait."
      explanation: The clinical report states the recessive disease model.
  notes: >-
    Reported disease alleles include splice-disrupting and missense variants.
    The 2024 Egyptian family carried a homozygous p.Met212Arg CAT variant; this
    entry does not infer broad genotype-phenotype correlations from individual
    families.
  evidence:
  - reference: PMID:39079473
    reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "ES revealed a new homozygous missense variant in the CAT gene segregating in the family, c .635 T > G (p.Met212Arg)."
    explanation: Exome sequencing identified a segregating homozygous CAT missense variant in affected siblings.
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Direct sequencing showed a clear splicing mutation of guanine to adenine substitution at the fifth position of intron 4 in the patient."
    explanation: A second human case documents a splice-region CAT disease allele.
treatments:
- name: Periodontal treatment and preventive oral care
  description: >-
    Individualized periodontal therapy and preventive oral care are the main
    case-supported management for symptomatic oral disease. A single long-term
    report found improved periodontal measurements and stable status after 15
    years; this is not evidence for a disease-modifying cure.
  action_category: THERAPEUTIC
  treatment_term:
    preferred_term: Dental Procedure
    term:
      id: NCIT:C38052
      label: Dental Procedure
  target_phenotypes:
  - preferred_term: Severe periodontitis
    term:
      id: HP:0000166
      label: Severe periodontitis
  - preferred_term: Oral ulcer
    term:
      id: HP:0000155
      label: Oral ulcer
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Besides, periodontal treatments and 15y follow-up were performed."
    explanation: The report directly documents sustained periodontal treatment and follow-up.
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the periodontal therapies have achieved a stable periodontal status."
    explanation: The observed stable status supports case-level periodontal management.
- name: Dental and periodontal surveillance
  description: >-
    Longitudinal dental evaluation can identify and follow destructive
    periodontitis in patients with oral disease. No universal visit interval is
    inferred from the single published long-term case.
  action_category: MONITORING
  treatment_term:
    preferred_term: dentist evaluation
    term:
      id: NCIT:C158323
      label: Dental Examination
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "periodontal treatments and 15y follow-up were performed."
    explanation: The case provides direct evidence for long-term periodontal follow-up without establishing a fixed schedule.
- name: Avoidance of hydrogen peroxide exposure
  description: >-
    Patients and procedural teams should avoid hydrogen peroxide-containing
    disinfection or oral-care exposures when alternatives are available because
    severe methemoglobinemia has occurred in catalase-deficient patients. The
    same review warns that rasburicase generates hydrogen peroxide and can
    produce methemoglobinemia and hemolysis in catalase deficiency.
  action_category: COUNSELING_INFORMATIONAL
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:24025477
    reference_title: "Inherited catalase deficiency: is it benign or a factor in various age related disorders?"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "During anesthesia for a Japanese acatalasemic patient the disinfection with hydrogen peroxide solution caused severe methemoglobinemia."
    explanation: The reported procedural complication supports an explicit peroxide-exposure precaution.
  - reference: PMID:24025477
    reference_title: "Inherited catalase deficiency: is it benign or a factor in various age related disorders?"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Patients with inherited catalase deficiency, who are treated with uric acid oxidase (rasburicase) may experience very high concentrations of hydrogen peroxide and may suffer from methemoglobinemia and hemolysis."
    explanation: The review supports specific caution when a therapy generates a high hydrogen peroxide burden.
- name: Genetic counseling and family evaluation
  description: >-
    Counseling can explain autosomal recessive recurrence and the distinction
    between biallelic acatalasia and heterozygous hypocatalasemia. Family enzyme
    testing and targeted molecular testing can identify affected relatives and
    carriers after a familial CAT variant is established.
  action_category: COUNSELING_INFORMATIONAL
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: NCIT:C15240
      label: Genetic Counseling
  evidence:
  - reference: PMID:13668563
    reference_title: Carrier state in human acatalasemia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The heterozygous carrier state of a rare hereditary disease, acatalasemia, has been defined biochemically."
    explanation: Family biochemistry demonstrates that the heterozygous carrier state can be identified.
  - reference: PMID:120431
    reference_title: Acatalasia in two Peruvian siblings.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Thirteen hypocatalasemic individuals, including both parents, were found among 29 relatives of the probands examined from four generations."
    explanation: Multigeneration family evaluation detected numerous hypocatalasemic carriers.
diagnosis:
- name: Quantitative erythrocyte catalase activity assessment
  description: >-
    Quantitative erythrocyte catalase activity is the defining biochemical
    assay. Marked or near-total deficiency supports acatalasia, while
    intermediate activity can suggest heterozygous hypocatalasemia; testing for
    a familial CAT variant is preferred for carrier confirmation. Oral findings
    alone are neither necessary nor sufficient because most affected people are
    asymptomatic.
  diagnosis_term:
    preferred_term: erythrocyte enzyme activity assessment
    term:
      id: NCIT:C25294
      label: Laboratory Procedure
  results: Markedly reduced erythrocyte catalase activity supports acatalasia; intermediate activity suggests carrier status and should be confirmed molecularly when a familial variant is known.
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Erythrocyte catalase activity was measured by ultraviolet spectrophotometer."
    explanation: The human report describes quantitative erythrocyte catalase measurement for diagnostic confirmation.
  - reference: PMID:13668563
    reference_title: Carrier state in human acatalasemia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Affected homozygotes have no blood catalase activity, whereas heterozygotes show activities intermediate between this inactivity and the activity of normal controls, without overlap."
    explanation: This historical family study supports a biochemical distinction among affected, carrier, and normal ranges without establishing universal modern cutoffs.
- name: CAT molecular genetic testing
  description: >-
    Sequencing CAT confirms the molecular diagnosis when biallelic pathogenic
    variants are identified and enables family-specific testing. Molecular
    confirmation is especially useful when oral phenotypes overlap other
    inherited periodontal disorders.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: NCIT:C19770
      label: Molecular Analysis
  results: Biallelic pathogenic CAT variants confirm CAT-related acatalasia in the appropriate biochemical context.
  evidence:
  - reference: PMID:24522161
    reference_title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "To confirm the diagnosis of acatalasemia, intron 4 of the catalase gene was amplified and sequenced."
    explanation: The report explicitly used CAT sequencing for diagnostic confirmation.
  - reference: PMID:39079473
    reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "ES revealed a new homozygous missense variant in the CAT gene segregating in the family, c .635 T > G (p.Met212Arg)."
    explanation: Exome sequencing established the molecular diagnosis in affected siblings with a periodontal phenocopy.
differential_diagnoses:
- name: Ehlers-Danlos syndrome, periodontitis type
  description: >-
    Periodontal Ehlers-Danlos syndrome can present with early destructive
    periodontitis, tooth mobility or loss, and connective-tissue findings. A
    recent acatalasia family was initially investigated for this condition
    because of joint hyperlaxity and gangrenous periodontitis.
  disease_term:
    preferred_term: Ehlers-Danlos syndrome, periodontitis type
    term:
      id: MONDO:0007527
      label: Ehlers-Danlos syndrome, periodontitis type
  distinguishing_features:
  - Markedly reduced erythrocyte catalase activity and biallelic CAT variants favor acatalasia.
  - A pathogenic C1R or C1S finding with the periodontal Ehlers-Danlos phenotype favors periodontal Ehlers-Danlos syndrome.
  evidence:
  - reference: PMID:39079473
    reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The patients were clinically suspected to have the periodontal type of Ehlers-Danlos syndrome and thus genetic testing of C1S and C1R causative genes was carried out first"
    explanation: The affected family directly demonstrates the periodontal Ehlers-Danlos clinical differential.
  - reference: PMID:39079473
    reference_title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "No pathogenic variants were detected in C1S and C1R genes then ES revealed a new homozygous missense variant in the CAT gene segregating in the family"
    explanation: Molecular testing resolved the phenocopy in favor of CAT-related acatalasia.
references:
- reference: PMID:120431
  title: Acatalasia in two Peruvian siblings.
- reference: PMID:11117918
  title: Hereditary catalase deficiencies and increased risk of diabetes.
- reference: PMID:13668563
  title: Carrier state in human acatalasemia.
- reference: PMID:19883754
  title: Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice.
- reference: PMID:22365890
  title: Acatalasemia and diabetes mellitus.
- reference: PMID:24025477
  title: "Inherited catalase deficiency: is it benign or a factor in various age related disorders?"
- reference: PMID:24522161
  title: Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
- reference: PMID:39079473
  title: "A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease)."
- reference: PMID:39085062
  title: The discovery of acatalasemia (lack of catalase in the blood) and its significance in human genetics.
review_notes: >-
  Re-reviewed comprehensively in July 2026. The revision narrows the disease
  identity to biallelic CAT-related, marked erythrocyte catalase deficiency;
  distinguishes usually asymptomatic acatalasia from the symptomatic Takahara
  oral presentation; rebuilds the oral peroxide-oxidation-necrosis mechanism;
  separates exposure-conditioned methemoglobinemia and an emerging,
  non-deterministic diabetes hypothesis; and adds structured genetics,
  biochemical diagnosis, case-calibrated management, a direct periodontal-EDS
  differential, and complete reference-catalog closure. Remaining gaps include
  unbiased modern natural-history cohorts, population-specific penetrance of
  oral disease, validated genotype-phenotype correlations, and prospective
  evidence for diabetes risk or management recommendations.
clinical_trials: []
datasets: []
📚

References & Deep Research

References

9
PMID:120431
Acatalasia in two Peruvian siblings.
No top-level findings curated for this source.
PMID:11117918
Hereditary catalase deficiencies and increased risk of diabetes.
No top-level findings curated for this source.
PMID:13668563
Carrier state in human acatalasemia.
No top-level findings curated for this source.
PMID:19883754
Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice.
No top-level findings curated for this source.
PMID:22365890
Acatalasemia and diabetes mellitus.
No top-level findings curated for this source.
PMID:24025477
Inherited catalase deficiency: is it benign or a factor in various age related disorders?
No top-level findings curated for this source.
PMID:24522161
Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis.
No top-level findings curated for this source.
PMID:39079473
A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease).
No top-level findings curated for this source.
PMID:39085062
The discovery of acatalasemia (lack of catalase in the blood) and its significance in human genetics.
No top-level findings curated for this source.