TY - CHAP M1 - Book, Section TI - Cytochrome b5 Reductase Deficiency and Enzymopenic Hereditary Methemoglobinemia A1 - Jaffé, Ernst R. A1 - Hultquist, Donald E. A2 - Valle, David L. A2 - Antonarakis, Stylianos A2 - Ballabio, Andrea A2 - Beaudet, Arthur L. A2 - Mitchell, Grant A. PY - 2019 T2 - The Online Metabolic and Molecular Bases of Inherited Disease AB - The major pathway for the reduction of methemoglobin to functional hemoglobin in human erythrocytes involves a NADH-dependent methemoglobin reductase system. In addition to NADH, this system requires the presence in the cytosol of both cytochrome b5 reductase, a 32,000-dalton protein, and cytochrome b5, a 12,000-dalton protein. These proteins are presumed to arise from larger parent molecules in the erythroid precursors by proteolytic cleavage of their hydrophobic tails.Enzymopenic hereditary methemoglobinemia (MIM 250800) is a rare recessively inherited disorder caused, in most cases, by deficiency of cytochrome b5 reductase only in erythrocytes (type I). Generalized cytochrome b5 reductase deficiency, demonstrable in all tissues that have been examined, occurs in 10 to 15 percent of cases and is accompanied by methemoglobinemia and severe, progressive, lethal neurologic disability (type II). Cytochrome b5 reductase deficiency limited to hematopoietic cells is also manifested by methemoglobinemia, but without neurologic effects (type III). Deficiency of cytochrome b5 may also lead to methemoglobinemia (type IV).The gene regulating the synthesis of cytochrome b5 reductase has been assigned to chromosome 22. Deficiency of cytochrome b5 reductase has a worldwide distribution, and electrophoretic variants of the enzyme with normal catalytic properties may have an incidence as high as 1:100. Heterozygotes for cytochrome b5 reductase deficiency are asymptomatic but have an increased propensity to develop toxic methemoglobinemia induced by drugs or other chemicals.The diagnosis of enzymopenic hereditary methemoglobinemia may be made by relatively simple laboratory determinations, but definition of the specific defect requires more sophisticated studies.Effective treatment may be provided by the administration of methylene blue, ascorbic acid, or riboflavin but is often not indicated, except for cosmetic reasons. Such therapy, however, has had no demonstrable effect on the neurologic aberrations in the generalized type II disorder. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/10/10 UR - ommbid.mhmedical.com/content.aspx?aid=1181456408 ER -