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Molybdenum cofactor deficiency: Mutations in GPHN, MOCS1, and MOCS2
Author(s) -
Reiss Jochen,
Hahnewald Rita
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21390
Subject(s) - sulfite oxidase , molybdenum cofactor , aldehyde oxidase , biology , cofactor , biochemistry , enzyme , gene , mutation , xanthine oxidase , oxidase test , xanthine dehydrogenase , genetics
All molybdenum‐containing enzymes other than the bacterial nitrogenase share an identical molybdenum cofactor (MoCo), which is synthesized via a conserved pathway in all organisms and therefore also is called “universal molybdenum cofactor.” In humans, four molybdoenzymes are known: aldehyde oxidase, mitochondrial amidoxime reducing component (mARC), xanthine oxidoreductase, and sulfite oxidase. Mutations in the genes encoding the biosynthetic MoCo pathway enzymes abrogate the activities of all molybdoenzymes and result in the “combined” form of MoCo deficiency, which is clinically very similar to isolated sulfite oxidase deficiency, caused by mutations in the gene for the corresponding apoenzyme. Both deficiencies are inherited as an autosomal‐recessive disease and result in progressive neurological damage and early childhood death in most cases. The majority of mutations leading to MoCo deficiency have been identified in the genes MOCS1 (type A deficiency), MOCS2 (type B deficiency), with one reported in GPHN. For type A deficiency an effective substitution therapy has been described recently. Hum Mutat 32:10–18, 2011. © 2010 Wiley‐Liss, Inc.