Acatalasemia - what is it ?

Maybe most of us don't familiar with this kind of disease. Acatalasemia is A disorder of peroxisomes characterized by a deficiency of erythrocyte catalase inherited as an autosomal recessive trait resulting in 2 clinical variants. Acatalasemia is often characterized by infection of the gums . Here's some facts about this disease :

EPIDEMIOLOGY

1. incidence: 1/250,000
2. age of onset: prior to puberty
3. 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