title: Prenatal diagnosis of heterozygosity for biotinidase deficiency by enzymatic and molecular analyses.
abstract: 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.
authors.affiliation: Department of Human Genetics, Medical College of Virginia/Virginia Commonwealth University, Richmond 23233, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Pomponio
authors.forename: J
authors.initials: J
authors.lastname: Hymes
authors.forename: A
authors.initials: A
authors.lastname: Pandya
authors.forename: B
authors.initials: B
authors.lastname: Landa
authors.forename: P
authors.initials: P
authors.lastname: Melone
authors.forename: R
authors.initials: R
authors.lastname: Javaheri
authors.forename: R
authors.initials: R
authors.lastname: Mardach
authors.forename: S W
authors.initials: SW
authors.lastname: Morton
authors.forename: G A
authors.initials: GA
authors.lastname: Meyers
authors.forename: T
authors.initials: T
authors.lastname: Reynolds
authors.forename: G
authors.initials: G
authors.lastname: Buck
authors.forename: W E
authors.initials: WE
authors.lastname: Nance
authors.forename: B
authors.initials: B
authors.lastname: Wolf
mesh_terms: D000581:Amidohydrolases / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D000653:Amniotic Fluid / Q000737:chemistry / Q000166:cytology; D043523:Biotinidase; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis*; D009154:Mutation; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D000581:Amidohydrolases; D043523:Biotinidase