Tay Sachs Disease: Analysis Of Australian Screening Strategies (1995-2013)

Abstract

Introduction: Tay Sachs Disease (TSD) is a fatal genetic disorder with autosomal recessive inheritance, occurring more frequently in Ashkenazi Jewish (AJ) populations. No cure or effective treatment exists. Carrier couples have a 1 in 4 risk that a baby will have TSD. The desire to prevent TSD inspired the first pre-conception genetic screening programs. The development of assisted reproductive technologies and pre-implantation genetic diagnosis of embryos has broadened reproductive options available for carrier-couples to avoid having a child with a serious genetic condition. Aim: My aims were to discover: • The allelic distribution of HEXA mutations in the Australian AJ community • The accuracy of TSD carrier risk self-determination in AJ individuals aged 20 to 40 years when questioned by health professionals • Evidence that TSD carrier screening prevents cases • Evidence of reported access to TSD screening • Evidence to make recommendations for primary care clinicians about TSD screening. • Clinical impacts and ethical issues raised by expanded genetic screening strategies. Methods: This thesis by publication represents my research work with Australian TSD screening programs (2008-2013). Results: A high TSD carrier frequency exists amongst Australian AJ individuals currently aged 20-40 years. Disclosure of AJ heritage can accurately predict TSD carrier risk. Screening programs have been effective in preventing TSD cases. Systematic review of the international literature on TSD screening formed NHMRC graded evidence-based best practice recommendations for primary care clinicians. Australasian clinical practice guidelines for genetic screening in Ashkenazi Jews are presented. Conclusion: Preconception genetic screening is effective in rare recessive disease prevention, with important implications for Australian health-economic policy.