THE MEASUREMENT OF 5′ ADENOSYICOBALAMIN IN SERUM MAY PROVIDE A RAPID METHOD OF DETERMINING THE CAUSE OF METHYLMALONIC ACIDEMIA

Abstract

Methylmalonic acidemia (MMA) is either due to a deficiency or a defective form of methylmalonyl-CoA mutase, or from deficient formation of the cobalamin (Cbl) cofactor for this enzyme, 5' deoxyadenosylcobalamin (ado-Cbl). It is important to establish the cause early because defective synthesis of ado-Cbl can respond to treatment with hydroxo-Cbl. A therapeutic trial with hydroxo-Cbl and analysis of fibroblast cultures for the mutase enzyme has been used to distinguish these forms. A 6 week old female was found to have MMA after presenting with vomiting and dehydration. Initial treatment included hydroxo-Cbl with protein restriction and the infant improved. Fibroblast cultures by genetic complementation indicated that the infant has an abnormality of methylmalonyl CoA mutase of mut class of mutations, generally unresponsive to hydroxo-Cbl. A specific RIA for ado-Cbl has become available and the serum concentration of this cofactor was 400pg/ml (normal 60-120pg/ml), while the infant was receiving hydroxo-Cbl indicating that there was no impairment in the synthesis of ado-Cbl. Thus, this provided additional evidence to the genetic complementation studies that established the defect in this infant to rest with the enzyme, methylmalonyl CoA mutase. The improvement continued after withdrawal of hydroxo-Cbl indicating that the initial response was due to the dietary restriction of protein.