MODULATION OF B-12 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 mate rnally administered cyanocobalamin (B-12) in attempts to ameliorate se quelae that include failure to thrive, developmental delay, dehydratio n, 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 B-12 to catalyze the reaction of methylmalonyl-coenzyme A to succinyl -coenzyme A. Methods. A 28-year-old woman, with a 3-year-old son affec ted with MMA, underwent amniocentesis at 15 weeks which showed a norma l karyotype, elevated amniotic fluid MMA, and decreased amniocyte 5'-d eoxyadenosylcobalamin, propionate, and methyl-tetrahydrofolate. MP and MU MMA levels were measured biweekly. B-12 doses were altered periodi cally according to laboratory-determine levels. Results. MP and MU lev els varied with gestational age and in response to increases in matern ally administered B-12 Conclusions. With increasing gestation, fetal, and placental size, increasing doses of B-12 are necessary to maintain MP and MU levels of MMA within normal range. The data suggest that cl ose surveillance and frequent measurements of MMA are necessary to pro perly titrate B-12 treatment.