Acatalasemia

A number sign (#) is used with this entry because acatalasemia is caused by homozygous mutation in the CAT gene (115500) on chromosome 11p13.

Description

Acatalasemia, also known as acatalasia, is a metabolic disorder characterized by a total or near total loss of catalase activity in erythrocytes. About half of cases originate from ulcerating oral gangrenes, and these cases are referred to as having Takahara disease. Half-normal levels of catalase in heterozygotes is referred to as hypocatalasemia or hypocatalasia (Ogata, 1991).

Clinical Features

Acatalasemia was first discovered in Japan by Takahara, an otolaryngologist who found that in cases of progressive oral gangrene, hydrogen peroxide applied to the ulcerated areas did not froth in the usual manner (Takahara and Miyamoto, 1948). Heterozygotes have an intermediate level of catalase in the blood. The frequency of heterozygotes is 0.09% in Hiroshima and Nagasaki but is of the order of 1.4% in other parts of Japan (Hamilton et al., 1961).

Acatalasia has been detected in Switzerland (Aebi et al., 1962) and in Israel (Szeinberg et al., 1963). In the Swiss and the Israelis the homozygotes showed some residual catalase activity, suggesting that this may be a different mutation from that responsible for the Japanese disease in which catalase activity is zero and no cross-reacting material has been identified.

Ogata (1991) compared the properties of residual catalase in the Japanese and Swiss forms of the disease and in the mutant mouse.

Shibata et al. (1967) found that an immunologically reactive but enzymatically inactive protein about one-sixth the size of active catalase is present in red cells of individuals with acatalasemia.

Goth and Eaton (2000) reported an increased frequency of diabetes in catalase-deficient (hypo/acatalasemic) Hungarian patients as compared with unaffected first-degree relatives and the general Hungarian population. The authors speculated that quantitative deficiency of catalase might predispose to cumulative oxidant damage of pancreatic beta-cells and resulting diabetes.

Inheritance

Acatalasemia is inherited as an autosomal recessive trait (Ogata, 1991).

Population Genetics

Ogata (1991) reported that 90 of 107 known individuals with acatalasemia were Japanese.

Goth et al. (2000) stated that the incidence of acatalasemia in Hungary in 5:106.

Molecular Genetics

In a Japanese patient with acatalasemia, Wen et al. (1990) identified a homozygous splice site mutation in the CAT gene (115500.0001).

In a Japanese patient with acatalasemia, Hirono et al. (1995) identified 1-bp deletion in the CAT gene (115500.0002).

In a Hungarian patient with acatalasemia, Goth et al. (2000) identified a homozygous insertion mutation in the CAT gene (115500.0003).

Animal Model

Hypocatalasia has been found in the guinea pig, dog, and domestic fowl (see review by Lush, 1966). In the acatalasemic mouse, Shaffer and Preston (1990) demonstrated that a CAG (glutamine)-to-CAT (histidine) transversion in the third position of codon 11 was responsible for the deficiency.