PARTIAL BIOTINIDASE DEFICIENCY IS USUALLY DUE TO THE D444H MUTATION IN THE BIOTINIDASE GENE

Newborn screening for biotinidase deficiency has identified children w ith profound biotinidase deficiency (<10% of mean normal serum activit y) and those with partial biotinidase deficiency (10%-30% of mean norm al serum activity). Children with partial biotinidase deficiency and w ho are not treated with biotin do not usually exhibit symptoms unless they are stressed (i.e., prolonged infection). We found that 18 of 19 randomly selected individuals with partial deficiency have the transve rsion missense mutation G1330>C, which substitutes a histidine for asp artic acid444 (D444H) in one allele of the biotinidase gene. We have p reviously estimated that the D444H mutation results in 48% of normal e nzyme activity for that allele and occurs with an estimated frequency of 0.039 in the general population. The D444H mutation in biotinidase deficiency is similar to the Duarte variant in galactosemia. The D444H mutation in one allele in combination with a mutation for profound de ficiency in the other allele is the common cause of partial biotinidas e deficiency.