Benign methylmalonic aciduria.
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency is usually considered to be a serious, often life-threatening disease. However, through routine screening of urine in neonates or screening of siblings of clinically affected neonates, we have identified eight children who have a benign clinical variant of this disorder. Their urinary methylmalonic acid levels have ranged from 1.0 to 3.4 mg per milligram of creatinine, with serum values ranging from an undetectable level to 1.7 mg per deciliter (130 nmol per liter). The children have not received dietary or vitamin therapy, have had normal growth and development (age range, 18 months to 13 years), and have performed as well as their unaffected siblings on psychometric testing. These children have no evidence of a deficiency of vitamin B12, which acts as a cofactor with methylmalonyl-CoA mutase, and they did not respond to the administration of vitamin B12. Two siblings were found by complementation analysis to have a defect in the methylmalonyl-CoA mutase apoenzyme; complementation analysis was not performed on the other patients. We conclude that the clinical spectrum of methylmalonyl-CoA mutase deficiency is wider than indicated by previously reported cases.
D000293:Adolescent; D001051:Apoenzymes / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D006128:Growth; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007360:Intelligence; D007535:Isomerases / Q000172:deficiency*; D008297:Male; D008314:Malonates / Q000652:urine*; D008764:Methylmalonic Acid / Q000652:urine*; D008765:Methylmalonyl-CoA Mutase / Q000172:deficiency*
D001051:Apoenzymes; D008314:Malonates; D008764:Methylmalonic Acid; D007535:Isomerases; D008765:Methylmalonyl-CoA Mutase