Mutations causing biotinidase deficiency in children ascertained by newborn screening in Western Hungary

In Hungary the national newborn screening programme for the detection of biotinidase deficiency was launched in 1989. In this study, we determined the genotypes of all patients identified at the Budapest Screening Centre that covers half of the country. The incidence of the disorder in Western Hungary is about three times the worldwide incidence. Overall, 21 different mutations were identified in 49 patients, including four novel mutations. Ten mutations proved to be unique to the Hungarian population

Molecular and clinical analysis of patients with classic and Duarte galactosemia in western Hungary

BACKGROUND: Classic galactosemia is an autosomal recessively inherited disorder caused by deficient activity of the enzyme galactose-1-phosphate uridyltransferase. The disorder can be detected by newborn screening and in Hungary the national screening program was launched in 1976 with two screening centers. The aim of this study was the molecular characterization of the genotypes and analysis of genotype-phenotype correlation among patients with classic or variant galactosemia. PATIENTS AND METHODS: DNA samples from 40 patients were analyzed by polymerase chain reaction followed by direct sequencing. RESULTS: 16 different sequence variations were identified, including two novel missense mutations (p.S297P, p.E146D). The two most common mutations were p. Q188R and p.K285N with allele frequencies of 45% and 31.2%, respectively. Clinical data were evaluated with respect to the genotypes found. CONCLUSIONS: The most serious clinical phenotypes in our population were associated with mutations p. Q188R, p.K285N, p.X380R, p.S297P, p.M142K, p.R.204X, p.Q169K and p.R407P, but manifestations depend on other genetic and environmental factors