Prenatal diagnosis of heterozygosity for biotinidase deficiency by enzymatic and molecular analyses.

Biotinidase deficiency is characterized by neurological and cutaneous abnormalities that can be prevented or ameliorated by oral biotin therapy. A child with biotinidase deficiency went undiagnosed for a long period and has irreversible neurological deficits despite biotin treatment. This child is homozygous for the most common mutation (G98:d7i3) found in symptomatic children with the disorder. The parents insisted on having prenatal diagnosis in a subsequent pregnancy to alleviate their anxiety about having another affected child. Mutation analysis of DNA obtained directly from amniotic fluid and from cultured amniocytes revealed that the fetus was heterozygous for the mutation. Maternal cell contamination of the amniocytes was excluded by genotype analysis. Biotinidase activity in extracts of cultured amniocytes revealed 40 per cent of mean normal activity. At birth, the infant was confirmed to be heterozygous by serum enzyme analysis. This is the first report of the use of molecular analysis for the prenatal diagnosis for biotinidase deficiency.