Abstract
Summary: From 1989 to 2001, 1 336 145 newborns were screened for biotinidase deficiency in Hungary. Fifty-eight children with the disorder were identified as enzyme-deficient. We have characterized the clinical and biochemical features and mutations of 20 of these children. Eleven children had profound biotinidase deficiency, 7 had partial biotinidase deficiency, and 2 were found to be heterozygous for profound deficiency by mutation analysis. Seventeen different mutations were identified in this population including seven novel mutations. Six of these new mutations are missense, 245C>A, 334G>A, 652G>C, 832C>G, 1253G>C, 1511T>A, and one is a unique allelic double mutation [212T>C;236G>A]. Of five Romanian Gypsies, four were homozygous for the 1595C>T mutation and one was heterozygous for this mutation. Most of the children with profound deficiency have been asymptomatic on therapy; however, four exhibited minimal brain abnormalities, motor delay and abnormal blood chemistries. Compliance with therapy must be questioned in these cases. Of clinical importance, all of the children with partial deficiency exhibited mild symptoms at the time of diagnosis, at several weeks to months of age. These symptoms resolved following biotin therapy. This is in contrast to the experience in the United States, where the children with partial deficiency have been asymptomatic at the time of diagnosis. This finding further indicates that children with partial deficiency should be treated. The incidence of biotinidase deficiency in Hungary is more than twice that observed in a worldwide survey. These results indicate that newborn screening in Hungary is effective and warranted.
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REFERENCES
Havass Z (1991) Neonatal screening for biotinidase deficiency in east Hungary. J Inherit Metab Dis 14: 928–931.
Heard GS, Secor McVoy JR, Wolf B (1984) A screening method for biotinidase deficiency in newborns. Clin Chem 30: 125–127.
Hymes J, Stanley CM, Wolf B (2001) Mutations in BTD causing biotinidase deficiency. Hum Mutat 200: 375–381.
Swango KL, Demirkol M, Huner G, et al (1998) Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene. Hum Genet 102: 571-575.
Wolf B (1991) Worldwide survey of neonatal screening for biotinidase deficiency. J Inherit Metab Dis 14: 923–927.
Wolf B (2001) Disorders of biotin metabolism. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 3935–3962.
Wolf B, Grier RE, Allen RJ, Goodman SI, Kien CL (1983) Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. Clin Chim Acta 131: 273–281.
Wolf B, Jensen K, Huner G, et al (2002) Seventeen novel mutations that cause profound biotinidase deficiency. Mol Genet Metab 77: 108–112.
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László, Á., Schuler, É.Á., Sallay, É. et al. Neonatal screening for biotinidase deficiency in Hungary: Clinical, biochemical and molecular studies. J Inherit Metab Dis 26, 693–698 (2003). https://doi.org/10.1023/B:BOLI.0000005622.89660.59
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DOI: https://doi.org/10.1023/B:BOLI.0000005622.89660.59