Cystathionine beta-synthase deficiency in Central Europe: discrepancy between biochemical and molecular genetic screening for homocystinuric alleles
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
PubMed
11748855
DOI
10.1002/humu.1239
PII: 10.1002/humu.1239
Knihovny.cz E-zdroje
- MeSH
- alely MeSH
- cystathionin-beta-synthasa krev genetika moč MeSH
- DNA chemie genetika MeSH
- genotyp MeSH
- homocystinurie enzymologie epidemiologie genetika MeSH
- incidence MeSH
- lidé MeSH
- mutace MeSH
- mutační analýza DNA MeSH
- novorozenec MeSH
- novorozenecký screening metody MeSH
- prevalence MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- cystathionin-beta-synthasa MeSH
- DNA MeSH
Recent reports suggested that homocystinuria due to cystathionine beta-synthase (CBS) deficiency is a more common inborn error of metabolism than originally thought. In this study we compared the prevalence of homocystinuric alleles ascertained by two different approaches. First, the incidence of homocystinuria estimated by selective biochemical screening in the Czech and Slovak Republics was 1:349,000 (95% CI 1:208,000-1:641,000). The two most common pathogenic mutant alleles found subsequently in these patients, IVS11-2A>C and c.833T>C, had a calculated population prevalence of 0.00042 (95% CI 0.00031-0.00055) and 0.00018 (95% CI 0.00013-0.00023), respectively. Second, to examine the possible negative detection bias of mildly affected patients we determined the prevalence of these two pathogenic mutations in a sample of 1284 unselected newborns. Indeed, the observed prevalence of the c.833T>C allele (0.00195, 95% CI 0.00063-0.00454) was 11x higher than in the previous group suggesting that many homozygotes for the c.833T>C had not been diagnosed by selective biochemical screening. The IVS11-2A>C allele was not detected among 2,568 newborn CBS alleles. The estimated incidence of homocystinuria of 1:83,000, calculated in a combined model, suggests that selective biochemical screening may ascertain only approximately 25% of all homocystinuric patients. In conclusion, homocystinuria in Central Europe may be sufficiently common to consider sensitive newborn screening programs for this disease.
Citace poskytuje Crossref.org
Vascular presentation of cystathionine beta-synthase deficiency in adulthood
OMIM
236200
