CONGENITAL DEFECT IN INTRACELLULAR COBALAMIN METABOLISM RESULTING IN HOMOCYSTINURIA AND METHYLMALONIC ACIDURIA .2. BIOCHEMICAL INVESTIGATIONS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 34  (5) , 483-496
Abstract
Biochemical investigations are reported in an infant with methylmalonic aciduria and homocystinuria who died at 4 mo. of age. Postmortem analysis of liver obtained 2 wk after the child was treated with vitamin B12 revealed deficient activity of cobalamin dependent enzymes: N5-methyltetrahydrofolate: homocysteine methyltransferase [MeTHF-HCy] (requiring Me-Cbl [methylcobalamin]), and methylmalonyl CoA [MMA-CoA] mutase (requiring Ado-Cbl [5''-deoxyadenosylcobalamin], MMA-CoA mutase activity could be restored to normal in vitro by added Ado-Cbl, but MeTHF-HCy transferase activity was not significantly enhanced by addition of Me-Cbl. Although the serum total cobalamin was normal, total cobalamin in liver and kidney was abnormally low. In the kidney Me-Cbl and Ado-Cbl were disproportionally decreased, whereas in the liver only Ado-Cbl was significantly reduced. At least some of the CN-Cbl administered was apparently converted to the coenzymes in liver which would explain the reduction of MMA- and HCy-excretion during therapy. This infant suffered from a congenital defect in 1 of the steps of intracellular cobalamin metabolism or transport common to the synthesis of both coenzymes; life-long treatment with vitamin B12 (OH-Cbl) may be of value in similar cases, particularly if given early in the course of the disease.