Tay-Sachs disease: current perspectives from Australia.

Tay-Sachs disease (TSD) is a fatal, recessively inherited neurodegenerative condition of infancy and early childhood. Although rare in most other populations, the carrier frequency is one in 25 in Ashkenazi Jews. Australian high-school-based TSD preconception genetic screening programs aim to screen, educate, and optimize reproductive choice for participants. These programs have demonstrated high uptake, low psychological morbidity, and have been shown to result in fewer than expected Jewish TSD-affected births over 18 years of operation. The majority of Jewish individuals of reproductive age outside of the high school screening program setting in Australia have not accessed screening. Recent recommendations advocate supplementing the community high school screening programs with general practitioner- and obstetrician-led genetic screening of Ashkenazi Jewish individuals for TSD and other severe recessive diseases for which this group is at risk. Massively parallel DNA sequencing is expected to become the testing modality of choice over the coming years.

Ashkenazi Jewish population screening for Tay-Sachs disease: the international and Australian experience.

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.

Tay Sachs disease in Australia: reduced disease incidence despite stable carrier frequency in Australian Jews.

OBJECTIVES: To evaluate the outcomes of preconception screening of Jewish Australians for Tay Sachs disease (TSD) carrier status on Jewish TSD-affected births. DESIGN, PARTICIPANTS AND SETTING: Epidemiological observational study involving a complete retrospective audit of infantile and intermediate TSD cases diagnosed in Sydney and Melbourne between 1 January 1995 and 31 December 2011 (Royal Children's Hospital Melbourne; Pacific Laboratory Medicine Services, Pathology North, NSW Health Pathology, Sydney; Victorian Clinical Genetics Services, Melbourne; and SA Pathology, Adelaide), and carrier frequency among Jewish high school students attending schools participating in TSD screening programs over the same period. MAIN OUTCOME MEASURES: Jewish TSD carrier frequency; and expected versus observed Jewish TSD-affected births. RESULTS: The 2006 Census indicated that most of the total 88,826 Jewish Australians live in Melbourne (46%) and Sydney (40%). The 7,756 Jewish high school students screened for TSD in Sydney and Melbourne during the study period had a carrier frequency of one in 31 (3.26%; 95% CI, 2.89%-3.68%).The estimated expected number of TSD-affected births in Melbourne and Sydney in 1995-2011 was 4.1 for Jewish births and 7.4 for other births (a ratio of Jewish to non-Jewish births of 1:2). The actual number was 12 (four in Sydney and eight in Melbourne), of which two were Jewish (a ratio of Jewish to non-Jewish births of 1:5). This finding of fewer than expected Jewish TSD cases coincided with a period during which screening programs were operating. There have been no Jewish TSD-affected children born to parents who were screened previously. CONCLUSION: Community education, appreciation of autosomal recessive inheritance and genetic carrier screening before pregnancy are the likely factors in our finding of fewer than expected Jewish babies with TSD. Ongoing outcome monitoring must continue.