Journal of Inherited Metabolic Disease

, Volume 26, Issue 7, pp 693–698

Neonatal screening for biotinidase deficiency in Hungary: Clinical, biochemical and molecular studies


  • Á. László
    • A. Szent-Györgyi Medical CentreUniversity of Szeged
  • É. Á. Schuler
    • PKU LaboratoryBudapest Children's Hospital
  • É. Sallay
    • A. Szent-Györgyi Medical CentreUniversity of Szeged
  • E. Endreffy
    • A. Szent-Györgyi Medical CentreUniversity of Szeged
  • Cs. Somogyi
    • PKU LaboratoryBudapest Children's Hospital
  • Á. Várkonyi
    • A. Szent-Györgyi Medical CentreUniversity of Szeged
  • Z. Havass
    • Department of PediatricsErzsébet Hospital, Laboratory
  • K. P. Jansen
    • General Clinical Research Center, Core LaboratoryUniversity of Connecticut School of Medicine
    • Department of PediatricsConnecticut Children's Medical Center and the University of Connecticut School of Medicine

DOI: 10.1023/B:BOLI.0000005622.89660.59

Cite this article as:
László, Á., Schuler, É.Á., Sallay, É. et al. J Inherit Metab Dis (2003) 26: 693. doi:10.1023/B:BOLI.0000005622.89660.59


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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© Kluwer Academic Publishers 2003