CAT – Acatalasia

The catalase gene (CAT) encodes the antioxidant enzyme catalase, which decomposes hydrogen peroxide into water and oxygen. Loss of function of CAT manifests as autosomal recessive acatalasemia (Acatalasia), characterized by near‐absent erythrocyte catalase activity and a spectrum ranging from asymptomatic to Takahara’s disease with oral ulcerations and gangrene.

Inheritance is autosomal recessive, with three families described: one Chinese boy homozygous for the intron 4 splice variant c.480+5G>A (PMID:24522161), two Egyptian siblings with a novel homozygous missense variant c.635T>G (p.Met212Arg) (PMID:39079473), and three Japanese cases harboring the recurrent c.480+5G>A splice mutation (PMID:1551654).

Segregation analysis demonstrated co‐segregation of biallelic variants with acatalasemia in the Egyptian family (one additional affected relative) and concordant enzymatic deficiency in all subjects tested. The variant spectrum comprises a recurrent intronic splice mutation (c.480+5G>A) and a novel missense change (c.635T>G (p.Met212Arg)), both predicted to abolish catalase activity. No hypomorphic or deep‐intronic alleles beyond these have been reported.

Functional assays consistently reveal <5% of normal erythrocyte catalase activity in affected individuals, confirming loss of enzymatic function. In the Chinese proband and Japanese subjects, ultraviolet spectrophotometry demonstrated residual activity of 4–5% of controls ([PMID:24522161]; [PMID:1551654]). Reporter and promoter studies of CAT variants further support impaired transcription and enzyme stability.

Mechanistically, biallelic loss‐of‐function alleles in CAT result in hydrogen peroxide accumulation, leading to mucosal ulceration, gangrene, and periodontitis under oxidative stress. These clinical and laboratory data have been replicated over >30 years, establishing a definitive gene–disease relationship. Additional polymorphisms in promoter and noncoding regions have been described but lack clear pathogenicity.

Key Take-home: Genetic testing for biallelic CAT variants is clinically actionable for diagnosing autosomal recessive acatalasemia, guiding management of oxidative stress–related complications.

References

• Clinica chimica acta; international journal of clinical chemistry • 2014 • Long-term follow-up evaluation of an acatalasemia boy with severe periodontitis. PMID:24522161
• Archives of oral biology • 2024 • A novel missense variant in CAT gene causing acatalasemia with gangrenous periodontitis (Takahara's disease). PMID:39079473
• Human genetics • 1992 • Detection of a common mutation of the catalase gene in Japanese acatalasemic patients. PMID:1551654

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