Defective ABCD4:LMBRD1 does not transport Cbl from lysosomal lumen to cytosol

ATP-binding cassette sub-family D member 4 (ABCD4) is thought to mediate the lysosomal export of cobalamin (Cbl aka vitamin B12) into the cytosol, making it available for the production of Cbl cofactors. Cbl is an important cofactor for correct haematological and neurological functions. Defects in ABCD4 can cause methylmalonic aciduria and homocystinuria, cblJ type (MAHCJ; MIM:614857), a genetically heterogeneous metabolic disorder of Cbl metabolism characterised by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinically, symptoms include feeding difficulties, poor growth, hypotonia, lethargy, anaemia and delayed development. Mutations causing MAHCJ include Y319C and E583Lfs*9 (Coelho et al. 2012).

ATP结合盒家族D亚家族成员4（ABCD4）被认为介导钴胺素（Cbl，亦称维生素B12）从溶酶体向细胞质的外排，使其可用于Cbl辅因子的合成。Cbl是维持血液和神经系统正常功能的重要辅因子。ABCD4基因的缺陷可导致甲基丙二酸尿症和同型半胱氨酸尿症，CblJ型（MAHCJ；MIM:614857），这是一种由Cbl代谢途径中辅酶腺苷钴胺素（AdoCbl）和甲基钴胺素（MeCbl）水平降低为特征的、遗传异质性的代谢性疾病。临床表现为喂养困难、生长不良、肌张力低下、嗜睡、贫血和发育迟缓。导致MAHCJ的突变包括Y319C和E583Lfs*9（Coelho等，2012年）。