High frequencies of biotinidase (BTD) gene mutations in the Hungarian population

J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S289-92. doi: 10.1007/s10545-010-9152-0. Epub 2010 Jun 15.


Biotinidase deficiency, an autosomal recessively inherited disorder, is characterized by neurologic and cutaneous symptoms and can be detected by newborn screening. In Hungary the national screening programme was launched in 1989 with two screening centres. Over 1,070,000 neonates from western Hungary were screened for biotinidase deficiency in the Budapest Screening Centre between 1989 and December 2008. In this period, 57 patients with profound or partial biotinidase deficiency from 50 families were identified through routine newborn screening. The incidence of the disorder in western Hungary is 1 in 18,700, which is about three times the worldwide incidence. Twenty-four different mutations were identified in patients including the c.406delC novel mutation in exon 3, which is a frameshift mutation. To better understand the background of the unusually high disease incidence, 100 healthy subjects from the Hungarian population were screened by PCR and RFLP for the frequencies of p.D444H, p.Q456H and p.A171T;p.D444H, the three most common BTD mutations. The frequencies were found to be 5.5, 0.5 and 0%, respectively. The results demonstrate that the frequencies of two of the most common biotinidase variant alleles are higher in the Hungarian population than in other Caucasian populations. This and the presence of a unique Hungarian mutation may explain the high incidence of biotinidase deficiency in Hungary.

MeSH terms

  • Adult
  • Biotinidase / genetics*
  • Biotinidase Deficiency / diagnosis
  • Biotinidase Deficiency / enzymology
  • Biotinidase Deficiency / epidemiology
  • Biotinidase Deficiency / genetics*
  • Case-Control Studies
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Hungary / epidemiology
  • Incidence
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mutation*
  • Neonatal Screening / methods
  • Predictive Value of Tests
  • Young Adult


  • Biotinidase

Associated data

  • OMIM/253260