Acatalasaemia

Synonyms: catalase deficiency, Takahara's disease

Superoxide dismutase catalyses the conversion of the superoxide anion into hydrogen peroxide that is a toxic substance. Catalase is an enzyme that catalyses the breakdown of hydrogen peroxide to oxygen plus water.

The genetic abnormality is on chromosome 11 at gene map locus 11p13.¹ Homozygotes for the gene have a marked deficiency of catalase and heterozygotes have an intermediate level. It has been suggested that the affinity of catalase for hydrogen peroxide is poor and that a more important enzyme is glutathione peroxidase.

A number of variants have been described but most cases of acatalasaemia are classified as either Japanese, Swiss or Hungarian type. The Japanese type is most severe. Homozygotes have very little catalase activity and often suffer from ulcerating oral lesions. Heterozygotes have about half normal level and are usually clinically normal. The Swiss type has an abnormal enzyme that still has some activity. The disease is less severe or they are often asymptomatic. The biochemistry and genetics of these 3 varieties are different.

Epidemiology

Although this is said to be a rare condition, the gene frequency in Japan is given as 1.5%. A study on people in Hiroshima and Nagasaki gave figures of 0.09%.² Although the paper came from the Atomic Bomb Casualty Commission in 1961, discussion in the paper centred around inbreeding effects and no suggestion was made that catalase activity may be important in surviving the aftermath of a nuclear explosion, including high levels of radiation. If this were so, it would account for the low level of acatalasaemia amongst survivors and their descendants.

Presentation

Most cases are asymptomatic and acatalasaemia may be seen as disease in search of some symptoms. Its clinical features include oral gangrene, altered metabolism of lipids, carbohydrate and homocysteine and an increased risk of diabetes mellitus.

• Oral lesions, especially progressive gangrene of the gums, appears to be the most common presentation where there is overt disease and severe enzyme deficiency. In the original case, presentation was progressive oral gangrene.³

• In most cases there is some catalase activity and so the disease appears to be benign but there may be risks of exposure to oxidants and a series of Hungarian patients found an excessive incidence of diabetes mellitus amongst those with catalase deficiency.⁴⁵

• The impaired ability to deal with oxidative stress may predispose to atherosclerosis.⁶ However, the levels of atherosclerosis and subsequent related diseases are not as high as one might expect in this group. This suggests that there may other natural antioxidants in vivo. There is extensive research on the role of antioxidants such as vitamins E and C in terms of protection; however, the evidence is inconclusive.

• There is evidence that catalase deficiency predisposes to skin damage by ultraviolet light.⁷

• There is a suggestion that catalase deficiency may be associated with aniridia (absence or defect of the iris), Wilms' tumour and mild-to-moderate mental deficiency.⁸

Investigations

Catalase activity is usually measured in the erythrocytes.

Management

The literature does not offer guidance on progressive oral gangrene, and patients should be referred to specialists urgently. However, prompt treatment of oral infections is advised. This should be followed by attention to oral hygiene.

Vitamin E supplementation in acatalasaemic mice protects against tumour formation.⁹ However, this has not been evaluated in humans.

Some recent work has reported that patients at risk of tumour lysis syndrome can develop very high hydrogen peroxide levels when given uric acid oxidase treatment.¹⁰ The cause of this is unclear and needs to be evaluated further.

Historical note: acatalasia was 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.