MUTATION IN A PUTATIVE GLYCOSYLATION SITE (N489T) OF BIOTINIDASE IN THE ONLY KNOWN JAPANESE CHILD WITH BIOTINIDASE DEFICIENCY

The only known Japanese child with biotinidase deficiency was identifi ed by newborn screening in Japan. He has 10.8% of mean normal serum bi otinyl-hydrolase activity and trace biotinyl-transferase activity. The mutation results in 16% of normal crossreacting material in serum wit h antibody to purified normal biotinidase. He is homozygous for a uniq ue mutation, A(1466) > C (Asn489Thr) in exon 4 of the biotinidase gene . The mutation appears to abolish a putative glycosylation site in a r egion in which other missense mutations have been identified, indicati ng that this region of the enzyme must be important for enzyme activit y. This mutation may affect secretion or stability of the enzyme in se rum. interestingly this child is now 8 years old, has not been on biot in supplementation for 3 years, and has remained asymptomatic. (C) 199 8 Academic Press.