Neonatal Screening for Biotinidase Deficiency: An Update

Abstract

Biotinidase (EC 3.5.1.12) hydrolyses biotin from small biotinyl peptides and biocytin that result from the proteolytic degradation of biotin-dependent holocarboxylases (Pispa, 1965; Craft et al., 1985). The released biotin can then be reutilized by the body. Biotinidase also appears to play an important role in the processing of biotin from dietary protein-bound sources (Wolf et al, 1984). We have shown that most individuals with late-onset multiple carboxylase deficiency have a primary defect in biotinidase activity (Wolf et al, 1983a). Children with this autosomal recessively inherited disorder may exhibit seizures, hypotonia, ataxia, alopecia, skin rashes, hearing loss and developmental delay, which may ultimately result in coma or death (Wolf et al, 1983b). Although most affected individuals have had metabolic ketoacidosis and organic aciduria, some have not. All children who have been diagnosed early have improved markedly after treatment with pharmacologic doses of biotin. Others who are diagnosed late often sustain neurologic abnormalities even after biotin therapy. Therefore, biotinidase deficiency qualifies for inclusion in a newborn screening programme for inherited metabolic disorders by satisfying three major criteria. First, symptoms of the disease do not appear at birth but usually occur at several months of age. Second, affected individuals may manifest serious physical and mental disability. Third, the disorder can be treated easily and effectively with vitamin supplementation. In order to determine the feasibility of screening and the incidence of biotinidase deficiency, we have conducted a pilot neonatal screening programme in the Commonwealth of Virginia.