EPIDEMIOLOGY
- incidence: 1/250,000
- age of onset: prior to puberty
- risk factors:
- familial - autosomal recessive
- chrom. #: 11p13
- gene: catalase
PATHOGENESIS
1. Catalase
structure:
- gene 34 kb in length with 12 introns and 13 exons
- gene codes for a protein of 526 aa but the erythrocycte catalase is 517 aa suggesting some sort of post-translational processing takes place
- a tetramer containing a ferric (heme) iron which reacts readily with hydrogen peroxide
- function:
-
- the main function is the conversion of hydrogen peroxide to water and oxygen
- catalase is part of a cluster of antioxidant enzymes (superoxide dismutase, peroxidases) which act in concert to protect cells against activated oxygen species (oxygen with an extra oxygen usually produced by neutrophils)
- protects hemoglobin against oxidation by hydrogen peroxoide and perhaps peroxide-mediated damage to DNA
2. Acatalasemia
considered to be a disorder of lipid metabolism and particularly the peroxisomes and a genetically heterogeneous disease with two major variants:
1. Japanese Variant
- mutation in the regulatory portion of the gene
- deficiency of catalase activity arises from the synthesis of an enzyme with low specific activity or from diminished synthesis
2. Swiss Variant
- mutation in the structural portion of the gene
- deficiency of catalase activity arises from the production of an unstable form of catalase
- catalase activity deficiency predisposes patients to infection by peroxide-generating bacteria such as streptococci and pneumococci as erythrocycte catalase may not be able to protect heterologous tissue from damage by exogenous hydrogen peroxide
- another hypothesis is that hydrogen peroxide accumulation in areas of infection may induce neutrophil dysfunction
- heterozygotes present as hypocatalasemia and are unaffected
CLINICAL FEATURES
1. Japanese Variant (Takahara Disease)
1. Oral Manifestations (50%)
- oral ulcerations and gangrene (streptococcal and pneumococcal infections may start as small lesions around the gingival-dental border or on the tonsils and develop into fulminating inflammatory processes causing extensive tissue destruction, i.e., gums)
- a relatively benign disease with no other clinical features
2. Swiss Variant
asymptomatic
INVESTIGATIONS
1. Serum
- reduced catalase activity in RBC's
- blood placed in contact with hydrogen peroxide turns brown and does not produce oxygen bubbles
MANAGEMENT
1. Supportive
- no treatment for underlying disorder
- multidisciplinary approach:
aggressive treatment of streptococcal and pneumococcal infections
close dental monitering and surgery if necessary