The prenatal diagnosis and prenatal treatment of a fetus with the neonatal-onset variant of biotin-responsive multiple carboxylase deficiency are described. Pre-amniocentesis maternal urinary organic-acid profiles were normal. Amniotic-fluid methylcitrate (17 weeks' gestation) was ten standard deviations above the control mean. Amniotic-fluid-cell propionyl CoA carboxylase, pyruvate carboxylase, and 3-methylcrotonyl CoA carboxylase activities were indistinguishable from activities in controls after cell growth in biotin-supplemented media. In contrast, growth in biotin-restricted media resulted in carboxylase activities significantly below control values. The fetus was considered to be affected, and the mother was begun on oral biotin at 231/2 weeks' gestation. The full-term baby girl exhibited no clinical or chemical aberrations during the first 4 days of life, before the start of postnatal biotin supplementation. Cord-blood biotin was 34 times the upper normal neonatal concentration. The diagnosis was confirmed by carboxylase assays on cultured skin fibroblasts obtained after birth; by slightly raised urinary organic-acid levels later in infancy; and by demonstration of· fibroblast holocarboxylase synthetase with an elevated Km(biotin) and a depressed Vmax. Growth and development of the baby have been normal to age 11/4 years on oral biotin. The prenatal diagnosis of neonatal-onset biotin-responsive multiple carboxylase deficiency can be made by means of enzymatic studies of amniotic-fluid cells. Amniotic-fluid methylcitrate should be a useful adjunct to enzymatic studies. Prenatal treatment was effective in our patient, and there was no apparent toxicity to mother or baby from biotin supplementation during the last 16 weeks of pregnancy.
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