Cystathionine beta-synthase deficiency in Central Europe: Discrepancy between biochemical and molecular genetic screening for homocystinuric alleles

SOKOLOVÁ, Jitka, B. JANOŠÍKOVÁ, JD TERWILLIGER, Tomáš FREIBERGER, JP KRAUS and Viktor KOŽICH. Cystathionine beta-synthase deficiency in Central Europe: Discrepancy between biochemical and molecular genetic screening for homocystinuric alleles. Human Mutation. 2001, vol. 18, No 6, 2 pp. ISSN 1059-7794.

Basic information

Original name

Cystathionine beta-synthase deficiency in Central Europe: Discrepancy between biochemical and molecular genetic screening for homocystinuric alleles

Name in Czech

Diskrepance mezi biochmeickým a molekulárně genetickým screeningem homocystinurických alel

Authors

SOKOLOVÁ, Jitka (203 Czech Republic), B. JANOŠÍKOVÁ (203 Czech Republic), JD TERWILLIGER (840 United States of America), Tomáš FREIBERGER (203 Czech Republic, guarantor), JP KRAUS (840 United States of America) and Viktor KOŽICH (203 Czech Republic)

Edition

Human Mutation, 2001, 1059-7794

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Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 6.134

RIV identification code

RIV/00216224:14110/01:00036078

Organization unit

Faculty of Medicine

Keywords in English

homocystinuria; prevalence; mutation screening; cystathione beta-synthase; CBS; Czech; Slovak; ARMS-PCR

Tags

ARMS-PCR, CBS, cystathione beta-synthase, Czech, homocystinuria, mutation screening, prevalence, Slovak

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Abstract

V originále

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 25% of all homocystinuric patients. In conclusion, homocystinuria in Central Europe may be sufficiently common to consider sensitive newborn screening programs for this disease.

In Czech

V této studii byla porovnána prevalence alel spojených s homocystinurií dvěma přístupy. Incidence homocystinurie na základě výsledků biochemického screeningu je 1:349000. Dvě nejběžnější alely genu pro cystathionin beta-syntázu (IVS11-2A>C a c.833T>C)detekované u těchto pacientů, mají kalkulovanou populační frekvenci 0.00042, resp. 0,00018. Výskyt obou alel byl stanoven v souboru 1284 neselektovaných novorozenců (0.0, resp. 0.00195) a z kombinovaného modelu byla vypočtena frekvence onemocnění v české populaci 1:83000. To znamená, že biochemický screening zachytí pouze 25 % pacientů s homocystinurií.