Newborn screening for biotinidase deficiency: pilot study and follow-up of identified cases

Biotinidase deficiency is an inborn error of biotin recycling that can result in an organic aciduria and developmental delay, seizures, alopecia, hypotonia and hearing loss. Early presymptomatic biotin treatment may prevent these complications and, on that basis, newborn screening for the disorder has been developed. In Massachusetts we conducted a one-year pilot study of newborn screening for biotinidase deficiency. Among 99,398 screened neonates, we identified three with profound biotinidase deficiency (1:33,000) and seven with partial deficiency (1:14,000). None of the infants had biochemical or clinical complications when evaluated. The three with profound deficiency were begun on biotin therapy and have thrived. Those with partial deficiency have received no therapy and have had normal growth and development. Transient biotinidase deficiency was overrepresented among low birth weight infants, as expected. Just as this pilot study ended, an infant in a neighboring state was diagnosed with biotinidase deficiency after coming to attention because of seizures, developmental delay and hearing loss. His newborn blood specimen retrieved from storage gave no activity on biotinidase screening. Newborn screening for biotinidase deficiency is effective in identifying cases and probably is of value in preventing irreversible complications from this disorder in at least some of the identified infants.