Mutation (Q456H) is the most common cause of profound biotinidase deficiency in children ascertained by newborn screening in the United States

Karen J. Norrgard, Robert J. Pomponio, Katie L. Swango, Jeanne Hymes, Thomas R. Reynolds, Gregory A. Buck, Barry Wolf*

*Corresponding author for this work

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Biotinidase deficiency is an autosomal recessive disorder that can result in neurologic and cutaneous symptoms if not treated with biotin supplementation. We have identified the most common cause of profound biotinidase deficiency in children ascertained by newborn screening in the United States. 1368A → C results in a substitution of histidine for glutamine 456 (Q456H) in exon D of the biotinidase gene. This mutation was found in at least one allele in 14 unrelated children from 27 different families or 15 of 54 alleles studied (28%). This mutation was not identified in 41 normal adults using SSCA, nor was it found in 296 normal newborns using allele-specific oligonucleotide analysis, suggesting that this change is not a polymorphism. In addition, biochemical data from a child homozygous for Q456H suggest that the aberrant enzyme has very low biotinyl-hydrolase activity, lacks biotinyl-transferase activity, and is not recognized by antibody prepared to purified, normal human biotinidase. The ethnic backgrounds of the parents contributing the Q456H allele are varied but are generally northern European.

Original languageEnglish (US)
Pages (from-to)22-27
Number of pages6
JournalBiochemical and Molecular Medicine
Volume61
Issue number1
DOIs
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Biochemistry

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