ABSTRACT
Inborn errors of cobalamin metabolism result in problems affecting multiple systems, including hematologic, neurologic, ophthalmologic, dermatologic, cardiovascular and renal. Exogenous cobalamin is internalized by carrier mediated endocytosis and converted to the active cobalamin derivatives adenosylcobalamin and methylcobalamin in the mitochondria and cytoplasm, respectively. In the past, most patients with inborn errors of cobalamin metabolism came to medical attention when they developed symptoms of their disorder. Mild methylmalonic aciduria occurs in patients with mutations affecting the methylmalonyl-CoA epimerase gene, which encodes methylmalonyl-CoA isomerase, the enzyme that catalyzes the step prior to mutase in propionyl-CoA metabolism. The cobalamin deficiency type C disorder is by far the most frequent cause of combined methylmalonic aciduria and homocystinuria. The methylmalonic aciduria type D and homocystinuria disorder was originally identified in 1970 in two brothers with combined methylmalonic aciduria and homocystinuria and relatively mild neurological problems.
