Abstract
A 30-month-old girl was found to have thecbl 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/24 h 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/24 h) followed by a rise in excretion toward pretreatment levels (range 317–485 mg/24 h) 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.
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Batshaw, M.L., Thomas, G.H., Cohen, S.R. et al. Treatment of thecbl B form of methylmalonic acidaemia with adenosylcobalamin. J Inherit Metab Dis 7, 65–68 (1984). https://doi.org/10.1007/BF01805805
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DOI: https://doi.org/10.1007/BF01805805