title: Treatment of the cbl B form of methylmalonic acidaemia with adenosylcobalamin.
abstract: A 30-month-old girl was found to have the cbl B mutant form of methylmalonic aciduria by complementation analysis of fibroblasts. She was unresponsive to hydroxycobalamin and was treated with intramuscular adenosylcobalamin (AdoCbl), the deficient coenzyme, at a dose of 1 mg/24h during a period of clinical stability. Serum cobalamin increased from 770 to 54 200 pg/ml. Mean urinary methylmalonic acid excretion was 409 mg/24 h prior to therapy. There was a transient fall in methylmalonic acid excretion during the first 5 days of therapy (range 167-245 mg/24h) followed by a rise in excretion toward pretreatment levels (range 317-485 mg/24h) during the second week of AdoCbl treatment. There was no change in plasma ammonia, glycine or serum bicarbonate level. We interpret the failure of this child to have a sustained and clinically significant response to AdoCbl as indicating that AdoCbl did not reach or enter the mitochondria intact, or in some other way was unavailable as a coenzyme for the methylmalonyl CoA mutase apoenzyme.
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000188:drug therapy / Q000235:genetics*; D000641:Ammonia / Q000097:blood; D001639:Bicarbonates / Q000097:blood; D002675:Child, Preschool; D003038:Cobamides / Q000627:therapeutic use*; D005260:Female; D005998:Glycine / Q000097:blood; D006801:Humans; D008314:Malonates / Q000097:blood*; D008764:Methylmalonic Acid / Q000097:blood* / Q000652:urine; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D001639:Bicarbonates; D003038:Cobamides; D008314:Malonates; D000641:Ammonia; D008764:Methylmalonic Acid; C000913:cobamamide; D014805:Vitamin B 12; D005998:Glycine