Coelho et al. have identified a new disease that results in failure to release vitamin B12 from lysosomes. Affected patients present with methylmalonic aciduria and hyperhomocysteinemia. This disorder is caused by mutations in ABCD4, a gene that encodes for an ABC transporter, which was previously thought to have peroxisomal localization and function. ABCD4 colocalizes with the lysosomal proteins LAMP1 and LMBD1, the latter of which is deficient in the cblF defect.

Posted by Nicola Brunetti-Pierri, MD, FACMG