A successful strategy for preimplantation diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

Preimplantation genetic diagnosis (PGD) involves the screening of biopsied cells from in vitro, fertilization (IVF) generated embryos. This procedure allows the selective transfer of unaffected embryos and thus may be prefera ble to prenatal diagnosis for couples at high risk of transmitting genetic defects to their offspring. In this way, termination of pregnancy is avoide d. We describe here the development and first clinical application of PCD f or medium-chain acyl-CoA dehydrogenase deficiency (MCAD). MCAD is a common inherited metabolic disorder affecting fatty acid beta oxidation. The condi tion is autosomal recessive with an incidence of 1/6000 1/15 000 live birth s in the UK. It presents usually within the first two years of life with fa sting-associated hypoketotic hypoglycaemia which may lead to coma and death . The strategy developed was based on multiplex fluorescent PCR, and adapte d for single cell detection, Mutation analysis was carried out using single -strand conformation polymorphism (SSCP) with fluorescent detection. The em bryos generated through IVF arrested on day two post-insemination and conse quently none were available for transfer; all available blastomeres were us ed to confirm the accuracy and reliability of the diagnostic assays. Copyri ght (C) 2000 John Wiley & Sons, Ltd.