Clinical or ATPase domain mutations in ABCD4 disrupt the interaction between the vitamin B₁₂-trafficking proteins ABCD4 and LMBD1.

ABSTRACT: Vitamin B₁₂ (cobalamin (Cbl)), in the cofactor forms methyl-Cbl and adenosyl-Cbl, is required for the function of the essential enzymes methionine synthase and methylmalonyl-CoA mutase, respectively. Cbl enters mammalian cells by receptor-mediated endocytosis of protein-bound Cbl followed by lysosomal export of free Cbl to the cytosol and further processing to these cofactor forms. The integral membrane proteins LMBD1 and ABCD4 are required for lysosomal release of Cbl, and mutations in the genes LMBRD1 and ABCD4 result in the cobalamin metabolism disorders cblF and cblJ. We report a new (fifth) patient with the cblJ disorder who presented at 7 days of age with poor feeding, hypotonia, methylmalonic aciduria, and elevated plasma homocysteine and harbored the mutati

SUBMITTER: Fettelschoss V 

PROVIDER: S-EPMC5512089 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature