Kj. Norrgard et al., MUTATION (Q456H) IS THE MOST COMMON-CAUSE OF PROFOUND BIOTINIDASE DEFICIENCY IN CHILDREN ASCERTAINED BY NEWBORN SCREENING IN THE UNITED-STATES, Biochemical and molecular medicine, 61(1), 1997, pp. 22-27
Biotinidase deficiency is an autosomal recessive disorder that can res
ult in neurologic and cutaneous symptoms if not treated with biotin su
pplementation. We have identified the most common cause of profound bi
otinidase deficiency in children ascertained by newborn screening in t
he United States. 1368A --> C results in a substitution of histidine f
or glutamine 456 (Q456H) in exon D of the biotinidase gene. This mutat
ion was found in at least one allele in 14 unrelated children hom 27 d
ifferent families or 15 of 54 alleles studied (28%). This mutation was
not identified in 41 normal adults using SSCA, nor was it found in 29
6 normal newborns using allele-specific oligonucleotide analysis, sugg
esting that this change is not a polymorphism. In addition, biochemica
l data from a child homozygous for Q456H suggest that the aberrant enz
yme has very low biotinyl-hydrolase activity, lacks biotinyl-transfera
se activity, and is not recognized by antibody prepared to purified, n
ormal human biotinidase. The ethnic backgrounds of the parents contrib
uting the Q456H allele are varied but are generally northern European.
(C) 1997 Acadamic Press.