Ashkenazi Jewish population screening for Tay–Sachs disease: The International and Australian experience

Abstract

Internationally, Tay-Sachs disease (TSD) preconception screening of Ashkenazi Jewish (AJ) individuals and couples has led to effective primary prevention of TSD. In Australia, adolescent preconception genetic screening programs operate mainly in Jewish community high schools. These existing programs offer an effective means of primary prevention of TSD, are cost effective and safe. However, in the broader Australian community TSD screening is not systematically performed and cases still occur in unscreened AJ individuals. In order to improve the effectiveness of Australian screening, there is a need for definitive guidelines for healthcare professionals to facilitate extension of the proven benefits of preconception TSD screening to all AJ individuals at risk. We performed a systematic review of the relevant literature relating to AJ pre-conception and antenatal screening for TSD. The evidence was assessed using an established National Health and Medical Research Council evidence grading system. Evaluations of efficacy of TSD screening programs design and execution, cost-benefit and cost-utility health economic evaluation, and population outcomes were undertaken. The results have been used to propose a model for universal AJ TSD preconception and antenatal screening for the primary care setting.

Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents

“…These studies, performed over 20 years, have shown high uptake rates and have not demonstrated adverse psychological consequences. 30,31 Ross summarizes many of these early studies and discusses potential concerns-including those about potential coercion, confidentiality, and the informed-consent process-with similar implementation in the US. 32 d ASHG recommends that carrier testing in children and adolescents not be performed through institutional or population-based approaches at this time.…”

Tay-Sachs disease

“…(35) In America, the total Jewish population is 6 470 600; the United States, Canada, Argentina, Mexico, Brazil and Uruguay have the highest figures. (35) Etiology By 2014, 134 mutations in the HexA gene (15q23-q24) encoding for subunit α of β-hexosaminidase A had been reported (13); some of these mutations are characteristic or common in some ethnic groups and geographic locations. (25,36,37) Jamali et al (38) established that in Ashkenazi Jewish patients, there were three prevalent mutations: an insertion of four-base duplications in exon 11 of the HexA gene (c.1274_1277dupTATC, 81%), a splicing mutation (c.1421 + 1G4C IVS12 + 1G4C, 15%) and a delayed mutation (c.805G4A, 2%).…”

“…(16) Prenatal screening for TSD was introduced in 1971 in the U.S. and throughout history its application has been directed only at Ashkenazi Jewish populations. (9,13,17) Between 2006 and early 2011, the median number of tests per month was 2 900, with an annual rate of 35 000; the analytical sensitivity and specificity for U.S. participants were 97.2% and 99.8%, respectively. (17) This screening has been associated with a >90% reduction in the incidence of the disease in populations that have been intervened, mainly in the USA, Israel and Canada.…”

Approach to diagnosis of metabolic diseases

“…However, it should be noted that some of these disorders are quite rare now in the era of prenatal diagnosis. For instance, the incidence of Tay Sachs disease in targeted Jewish populations is extremely low worldwide [28,29].…”