Abstract
Biotinidase deficiency is an inherited metabolic disorder characterized by neurological and cutaneous symptoms. Fortunately, it can be treated and the symptoms prevented by oral administration of the vitamin biotin. Using dried blood-soaked filter paper cards, biotinidase activity was determined in the sera of 225,136 newborns in Brazil. Mutation analysis performed on DNA from 21 babies with low serum biotinidase activity confirmed that 3 had profound biotinidase deficiency (less than 10% of mean normal sera biotinidase activity), 10 had partial biotinidase deficiency (10 to 30% of mean normal serum activity), 1 was homozygous for partial biotinidase deficiency, 4 were heterozygous for either profound or partial deficiency, and 3 were normal. Variability in serum enzyme activities and discrepancies with mutation analyses were probably due to inappropriate handling and storage of samples sent to the laboratory. Obtaining an appropriate control serum at the same time as that of the suspected child will undoubtedly decrease the false-positive rate (0.09%). Mutation analysis can be used to confirm the genotype of these children. The estimated incidence of biotinidase deficiency in Brazil is about 1 in 9,000, higher than in most other countries. Screening and treatment of biotinidase deficiency are effective and warranted. These results strongly suggest that biotinidase deficiency should be included in the newborn mass screening program of Brazil.
Highlights
Because biotinidase deficiency meets the criteria for inclusion in newborn screening programs, at least 25 countries have included the disorder in their programs [5]
We report our experience with screening newborns for biotinidase deficiency from October 1995 to November 1999 in a private neonatal screening program in Southern Brazil
Because there are multiple factors that can result in falsely low enzyme activity, the highest enzyme activity of a child was likely to represent the true activity. Based on these enzyme results, it would be expected that some of the children initially thought to have profound or partial biotinidase deficiency would be heterozygous for the disorder or would not have a mutation at all
Summary
Based on the high incidence of biotinidase deficiency found through the currently available private screening programs in Brazil, more widespread screening will undoubtedly identify many more children with the disorder. Confirmation of biotinidase activity in serum was obtained for babies suspected of having the deficiency and for their parents by a quantitative colorimetric assay using biotinyl-p-aminobenzoate as described previously [2]. Blood for DNA was obtained from 21 children with serum enzyme activity below 30% of the mean activity of normal children to confirm and identify mutations by direct sequencing [7,8].
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