title: Congenital defect in intracellular cobalamin metabolism resulting in homocystinuria and methylmalonic aciduria. II. Biochemical investigations.
abstract: Biochemical investigations are reported in an infant with methylmalonic aciduria and homocystinuria who died at 4 months of age. Postmortem analysis of liver obtained 2 weeks after the child was treated with vitamin B12 revealed deficient activity of both cobalamin dependent enzymes: N5-methyltetrahydrofolate: homocysteine methyltransferase (requiring Me-Cbl), and methylmalonyl CoA mutase (requiring Ado-Cbl). 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. Though 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. This suggests that at least some of the CN-Cbl administered was converted to the coenzymes in liver which would explain the reduction of MMA- and HCy-excretion during therapy. The results show 1. that this infant suffered from a congenital defect in one of the steps of intracellular cobalamin metabolism or transport common to the synthesis of both coenzymes, 2. that 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.
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D003067:Coenzymes / Q000378:metabolism; D006712:Homocystinuria / Q000209:etiology; D006801:Humans; D007223:Infant; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000378:metabolism*; D008764:Methylmalonic Acid / Q000652:urine; D008765:Methylmalonyl-CoA Mutase / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D000596:Amino Acids; D003067:Coenzymes; D008764:Methylmalonic Acid; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D008765:Methylmalonyl-CoA Mutase; D014805:Vitamin B 12