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- Title
Molecular characterisation of 34 patients with biotinidase deficiency ascertained by newborn screening and family investigation.
- Authors
Mühl, Adolf; Möslinger, Dorothea; Item, Chike B; Stöckler-Ipsiroglu, Silvia
- Abstract
This study characterises the spectrum of biotinidase mutations in 21 patients (17 families) with profound biotinidase deficiency (BD) and 13 unrelated patients with partial BD using a denaturing gradient gel electrophoretic mutation screening and selective sequencing approach. In 29 from 30 unrelated families we found biallelic mutations including four common mutations, D444H (frequency 23.3%), G98:dTi3(20.0%), Q456H(20.0%), T532M (15.0%) and nine rare mutations (V62M, R157H, A171T+D444H, C423W, D543H, L279W, N172S, V109G, 12236G-A) with frequencies less than 5.0%. Only three profound BD patients with G98:dTi3/G98:dTi3 and Q456H/Q456H genotypes and residual biotinidase activities of 0.0%, and 0.9% of normal activity developed clinical symptoms before biotin supplementation at 8 weeks of age. All other patients remained asymptomatic within the first months of life or even longer without treatment. Two patients homozygous for the frameshift mutation G98:dTi3 had no measurable residual enzyme activity. Twelve patients with partial BD had the D444H mutation in at least one allele. We conclude that, based on mutation analysis and biochemical examinations of the enzyme, it is currently not clearly predictable whether an untreated patient will develop symptoms or not, although it seems that patients with activities lower than 1% are at a high risk for developing symptoms of the disease early in life.
- Subjects
GENETIC disorders; BIOTIN; GENETIC mutation
- Publication
European Journal of Human Genetics, 2001, Vol 9, Issue 4, p237
- ISSN
1018-4813
- Publication type
Article
- DOI
10.1038/sj.ejhg.5200620