Department of Human Genetics, McGill University, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Department of Human Genetics, McGill University, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Vitam Horm. 2022;119:355-376. doi: 10.1016/bs.vh.2022.01.010. Epub 2022 Feb 21.
Cobalamin (vitamin B) is required for activity of the enzymes methylmalonyl-CoA mutase and methionine synthase in human cells. Inborn errors affecting cobalamin uptake or metabolism are characterized by accumulation of the substrates for these enzymes, methylmalonic acid and homocysteine, in blood and urine. Inborn errors affecting synthesis of the adenosylcobalamin coenzyme required by methylmalonyl-CoA mutase (cblA and cblB) result in isolated methylmalonic aciduria; inborn errors affecting synthesis of the methylcobalamin coenzyme required by methionine synthase (cblE and cblG) result in isolated homocystinuria. Combined methylmalonic aciduria and homocystinuria is seen in patients with impaired intestinal cobalamin absorption (intrinsic factor deficiency, Imerslund-Gräsbeck syndrome) and with defects affecting synthesis of both cobalamin coenzymes (cblC, cblD, cblF and cblJ). A series of disorders caused by pathogenic variant mutations affecting gene regulators (transcription factors) of the MMACHC gene have recently been described (HCFC1 [cblX disorder] and deficiencies of THAP11, and ZNF143 [the cblK disorder]).
钴胺素（维生素 B）是人体内甲基丙二酰辅酶 A 变位酶和蛋氨酸合成酶活性所必需的。影响钴胺素摄取或代谢的先天性错误的特征是这些酶的底物，甲基丙二酸和同型半胱氨酸，在血液和尿液中的积累。影响甲基丙二酰辅酶 A 变位酶所需的腺苷钴胺素辅酶合成的先天性错误（cblA 和 cblB）导致孤立性甲基丙二酸尿症；影响蛋氨酸合成酶所需的甲基钴胺素辅酶合成的先天性错误（cblE 和 cblG）导致孤立性同型胱氨酸尿症。吸收不良（内因子缺乏症，Imerslund-Gräsbeck 综合征）和影响两种钴胺素辅酶合成的缺陷（cblC、cblD、cblF 和 cblJ）的患者会出现甲基丙二酸尿症和同型胱氨酸尿症。最近描述了一系列由影响 MMACHC 基因基因调节剂（转录因子）的致病性变异突变引起的疾病（HCFC1[cblX 疾病]和 THAP11 缺乏症，以及 ZNF143[cblK 疾病]）。
