Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Evans, M.I. et al.

Modulation of B12 dosage and response in fetal treatment of methylmalonic aciduria (MMA): titration of treatment dose to serum and urine MMA.

OBJECTIVE: Prenatally diagnosed methylmalonic aciduria (MMA) has been treated in only a few fetuses, and has been done empirically with maternally administered cyanocobalamin ( B12) in attempts to ameliorate sequelae that include failure to thrive, developmental delay, dehydration, and coma. There has not been a systematic attempt to titrate doses to fetal response. We investigated the alterations in maternal dosage necessary to keep maternal plasma (MP) and urine (MU) levels of MMA in the normal range secondary to the ability of pharmacological doses of B12 to catalyze the reaction of methylmalonyl-coenzyme A to succinyl-coenzyme A. METHODS: A 28-year-old woman, with a 3-year-old son affected with MMA, underwent amniocentesis at 15 weeks which showed a normal karyotype, elevated amniotic fluid MMA, and decreased amniocyte 5'-deoxyadenosylcobalamin, propionate, and methyl-tetrahydrofolate. MP and MU MMA levels were measured biweekly. B12 doses were altered periodically according to laboratory-determined levels. RESULTS: MP and MU levels varied with gestational age and in response to increases in maternally administered B12. CONCLUSIONS: With increasing gestation, fetal, and placental size, increasing doses of B12 are necessary to maintain MP and MU levels of MMA within normal range. The data suggest that close surveillance and frequent measurements of MMA are necessary to properly titrate B12 treatment.[1]

References

Modulation of B12 dosage and response in fetal treatment of methylmalonic aciduria (MMA): titration of treatment dose to serum and urine MMA. Evans, M.I., Duquette, D.A., Rinaldo, P., Bawle, E., Rosenblatt, D.S., Whitty, J., Quintero, R.A., Johnson, M.P. Fetal. Diagn. Ther. (1997) [Pubmed]

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