Genetic and Biochemical Studies of Hereditary Methemoglobinemia (NADH-Cytochrome b5 Reductase Deficiency

Genetic and Biochemical Studies of Hereditary Methemoglobinemia (NADH-Cytochrome b5 Reductase Deficiency

Creators Shirabe Komei

Creators Yubisui Toshitsugu

Creators Takeshita Masazumi

Hereditary methemoglobinemia is an autosomal recessive disorder caused by a deficiency of NADH-cytochrome b5 reductase. In most cases enzyme deficiency occurs in red cells and symptom is only cyanosis due to elevated methemoglobin (type I). In about 10% of the cases deficiency is demonstrated in all the examined tissues and is accompanied by methemoglobinemia and severe neurological disorders (type II). Gene analyses of five independent families with I disease showed that point mutations leading to amino acid substitutions occur in all cases. Mutations found in three patients of type II disease were a point mutation, a deletion of 3 bases that leads to one amino acid deletion, and a mutation of splicing acceptor site of exon 9. Charasterization of recombinant type I and type II mutant enzymes syowed that type Ienzymes retained high enzyme activity but were unstable, wherews type II enzymes had low catalytic ability. Mutations in type I disease on three dimensional styucture of the enzyme residein the marginal portion of the enzyme that seem to participate in maintaining the enzyme structure, explain low catalytic efficiency of mutants.

[ISSN]0513-1812

[NCID]AA00594272