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 methylmalonylcoenzyme 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 methyltetrahydrofolate. MP and MU MMA levels were measured biweekly. B12doses 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 ges4tation, 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.
- Fetal therapy
- Methylmalonic aciduria
- Prenatal diagnosis
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Radiology Nuclear Medicine and imaging
- Obstetrics and Gynecology