The
enzyme catalase is the main regulator of
hydrogen peroxide metabolism. Recent findings suggest that a low concentration of
hydrogen peroxide may act as a messenger in some signalling pathways whereas high concentrations are toxic for many cells and cell components.
Acatalasemia is a genetically heterogeneous condition with a worldwide distribution. Yet only two Japanese and three Hungarian syndrome-causing mutations have been reported. A large-scale (23 130 subjects)
catalase screening program in Hungary yielded 12 hypocatalasemic families. The V family with four hypocatalasemics (60.6 +/- 7.6 MU/L) and six normocatalasemic (103.6 +/- 23.5 MU/L) members was examined to define the mutation causing the syndrome. Mutation screening yielded four novel polymorphisms. Of these, three intron sequence variations, namely G-->A at the
nucleotide 60 position in intron 1, T-->A at position 11 in intron 2, and G-->T at position 31 in intron 12, are unlikely to be responsible for the decreased blood
catalase activity. However, the novel G-->A mutation in exon 9 changes the
essential amino acid Arg 354 to Cys 354 and may indeed be responsible for the decreased
catalase activity. This inherited
catalase deficiency, by inducing an increased
hydrogen peroxide steady-state concentration in vivo, may be involved in the early manifestation of
type 2 diabetes mellitus for the 35-year old proband.