Cystathionine beta-synthase deficiency in Central Europe: discrepancy between biochemical and molecular genetic screening for homocystinuric alleles
Language English Country United States Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
11748855
DOI
10.1002/humu.1239
PII: 10.1002/humu.1239
Knihovny.cz E-resources
- MeSH
- Alleles MeSH
- Cystathionine beta-Synthase blood genetics urine MeSH
- DNA chemistry genetics MeSH
- Genotype MeSH
- Homocystinuria enzymology epidemiology genetics MeSH
- Incidence MeSH
- Humans MeSH
- Mutation MeSH
- DNA Mutational Analysis MeSH
- Infant, Newborn MeSH
- Neonatal Screening methods MeSH
- Prevalence MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Names of Substances
- Cystathionine beta-Synthase 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.
References provided by Crossref.org
Vascular presentation of cystathionine beta-synthase deficiency in adulthood
OMIM
236200
