Prenatal Therapy Of Holocarboxylase Synthetase Deficiency

A 25y.o. G4P3Ab. woman who had previously delivered at least one and possibly two infants affected with a holocarboxylase synthetase deficiency was given biotin, 10mg p.o. daily over the last 4 wks. of pregnancy. No attempt at amniocentesis was made because of the late gestational stage of presentation. Twin male infants were delivered by elective C-section at 40 wks. gestation. Fibroblast cultures were begun immediately after birth, assay of which subsequently showed one infant to be normal and the other affected. However, daily monitoring of organic acids in urine and plasma over the first week of life showed no abnormality in either infant, both of whom appeared phenotypically normal. The subsequent clinical course of the affected baby has been reported elsewhere and documented clear biotin-responsiveness of the defect in vivo. Biotin measurements provided evidence that biotin administration during late pregnancy was effective in raising cord blood biotin to 4-7 fold control levels (30-48ng/ml vs. 7.34±0.55ng/ml). We conclude that it is possible to safely and effectively raise fetal blood biotin to therapeutic levels by oral administration of 10mg daily to the mother, in this case obviating the need for prenatal diagnosis and its attendant risks.