Acatalasia (acatalasemia, catalase deficiency) is a rare genetic condition displaying a pattern of autosomal recessive inheritance. The catalase enzyme catalyzes the breakdown of hydrogen peroxide, a dangerous compound with oxidizing potential, into water and oxygen. Low levels of enzyme activity may lead to tissue damage under some conditions such as an infection by certain bacteria because a defense against the oxidative effects of hydrogen peroxide is compromised. However, other enzymes also function in the decomposition of hydrogen peroxide, which helps to ameliorate the effect of low catalase levels. Another reason for the condition being benign is that absence of catalase is rarely complete, and some residual activity can usually be found.

A variety of mutations may be responsible for the enzyme deficiency. As a result, the nature of the defect in the protein and the clinical manifestations vary. Until now, three main types of acatalasia have been distinguished (there are relevant subtypes, too). The first is the Japanese type, which is also the type that was first described. The condition of acatalasia was originally identified when a patient with mouth sores underwent surgery and on rinsing the wounds with hydrogen peroxide no bubbles were observed, indicating the absence of catalase activity [1]. The Japanese type of acatalasia, also called Takahara disease, is often characterized by mouth sores and gangrenes, although the incidence of oral problems is decreasing as oral care keeps improving. The second type was identified in Switzerland [2]. People having this condition are often free of symptoms. The third type of acatalasia, described in Hungary, is variable and is frequently associated with type II diabetes [3].

In addition to diabetes mellitus, atherosclerosis, Wilms tumor, and aniridia can be associated with acatalasia [4]. In patients with acatalasia, the high levels of hydrogen peroxide may lead to methemoglobinemia. This may be a particular concern for acatalasemic patients undergoing uric acid oxidase treatment during chemotherapy because this can result in very high concentrations of hydrogen peroxide [5].

Patient history and physical examination are indispensable for discovering the signs (mainly mouth sores or gangrenes) suggestive of acatalasia. Verification of the disease can be made by the simple test of exposing blood to hydrogen peroxide to observe the features of acatalasia, which are the absence of bubbles and the blood turning very quickly brown. Since many people with acatalasia are asymptomatic, they are often diagnosed through screening.

Full diagnosis requires the physicochemical characterization of the protein and the molecular genetic identification of the defect.

The enzyme activity can be measured in red blood cells. The molecular weight, isoelectric point, thermal stability, and catalytic constants of the catalase from patients with the Japanese acatalasia I condition are the same as those of the normal enzyme; however, the quantity of the protein is severely diminished [6]. In contrast, the Swiss-type enzyme – and some of the Hungarian types - have altered features, among them a decreased stability, showing that the protein is defective.

Molecular characterization of sequence alterations causing acatalasia shows heterogeneity among the patients. In the Japanese acatalasia I condition, sequencing of the gene and other studies demonstrated a splicing mutation [7]. Point mutations causing decreased activity of the enzyme have been observed in some Hungarian type conditions [8], whereas frameshift mutations were found in Hungarian and some Japanese patients [9] [10].

There is no specific cure for acatalasia, but treatment focuses on managing symptoms and preventing complications. Regular dental check-ups and good oral hygiene are crucial to prevent infections. In cases of severe oral gangrene, surgical intervention may be necessary. Antioxidant therapy, such as vitamin C and E supplements, may help reduce oxidative stress. Patients should also avoid exposure to substances that can increase hydrogen peroxide levels, such as certain drugs and foods.

The prognosis for individuals with acatalasia varies depending on the severity of the enzyme deficiency and the presence of symptoms. Many people with acatalasia lead normal, healthy lives with minimal intervention. However, those with severe symptoms may experience recurrent infections and require ongoing medical care. Early diagnosis and management are key to preventing complications and improving quality of life.

Acatalasia is caused by mutations in the CAT gene, which provides instructions for producing catalase. These mutations lead to reduced or absent enzyme activity. The disorder is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. Carriers, with only one mutated gene, typically do not show symptoms.

Acatalasia is an extremely rare condition, with a higher prevalence in certain populations, such as in Japan and Switzerland. The exact incidence is unknown, but it is estimated to affect fewer than 1 in 1,000,000 people worldwide. The rarity of the disorder makes it challenging to study, and many cases may go undiagnosed due to mild or absent symptoms.

In individuals with acatalasia, the lack of catalase activity leads to the accumulation of hydrogen peroxide in cells. This accumulation can cause oxidative stress, damaging cellular components like DNA, proteins, and lipids. The oral cavity is particularly susceptible to damage due to constant exposure to bacteria and other irritants, leading to the characteristic symptoms of mouth ulcers and infections.

As a genetic disorder, acatalasia cannot be prevented. However, genetic counseling is recommended for families with a history of the condition to understand the risks of passing it on to offspring. For affected individuals, preventive measures focus on minimizing exposure to factors that can increase hydrogen peroxide levels and maintaining good oral hygiene to prevent infections.

Acatalasia is a rare genetic disorder resulting from a deficiency of the enzyme catalase, leading to the accumulation of hydrogen peroxide in the body. While many individuals remain asymptomatic, some may experience recurrent oral infections and other complications. Diagnosis involves enzyme activity assays and genetic testing. Management focuses on symptom control and prevention of complications, with a generally favorable prognosis for most patients.

If you or a family member has been diagnosed with acatalasia, it's important to understand that this is a rare genetic condition affecting the body's ability to break down hydrogen peroxide. While it can lead to oral health issues, many people with acatalasia live normal lives with proper care. Regular dental visits and good oral hygiene are essential. If you have concerns about your health or genetic risks, consider speaking with a healthcare provider or genetic counselor for personalized advice and support.

1. Takahara S, Miyamoto H. The progressive, necrotic dental maxillitis that was considered to be the cause of the lack of catalase in the blood. Okayama Igakkai zasshi. 1948;60(1-2):90.
2. Aebi H, Jeunet F, Richterich R, et al. Observations in two Swiss families with acatalasia. Enzymol Biol Clin (Basel). 1962-1963;2:1-22.
3. Góth L, Eaton JW. Hereditary catalase deficiencies and increased risk of diabetes. Lancet. 2000;356(9244):1820-1821.
4. Turleau C, de Grouchy J, Tournade MF, Gagnadoux MF, Junien C. Del 11p/aniridia complex. Report of three patients and review of 37 observations from the literature. Clin Genet. 1984;26(4):356-362.
5. Góth L, Bigler NW. Catalase deficiency may complicate urate oxidase (rasburicase) therapy. Free Radic Res. 2007;41(9):953-935.
6. Ogata M, Tomokuni K, Watanabe S, Osaki H, Sadamoto M. Residual catalase in the blood of Japanese acatalasemia. Tohoku J Exp Med. 1972;107(2):105-114.
7. Wen JK, Osumi T, Hashimoto T, Ogata M. Molecular analysis of human acatalasemia. Identification of a splicing mutation. J Mol Biol. 1990;211(2):383-393.
8. Góth L, Vitai M, Rass P, Sükei E, Páy A. Detection of a novel familial catalase mutation (Hungarian type D) and the possible risk of inherited catalase deficiency for diabetes mellitus. Electrophoresis. 2005;26(9):1646-1649.
9. Góth L, Shemirani A, Kalmár T. A novel catalalase mutation (a 
GA Insertion) causes the Hungarian Type of Acatalasemia. Blood Cells Mol Dis. 2000;26(2):151-154.
10. Hirono A1, Sasaya-Hamada F, Kanno H, Fujii H, Yoshida T, Miwa S. A novel human catalase mutation (358 T-->del) causing Japanese-type acatalasemia. Blood Cells Mol Dis. 1995;21(3):232-234.