Delivery of a normal baby after preimplantation genetic diagnosis for non-ketotic hyperglycinaemia

Abstract Non-ketotic hyperglycinaemia (NKH), or glycine encephalopathy, is an autosomal recessive neurometabolic disease caused by defective activity of the glycine cleavage system. Up to 80% of NKH cases are caused by mutations in the P protein encoded by the glycine decarboxylase ( GLDC ) gene. GLDC deletions were identified in approximately 20% of NKH mutant alleles and resulted in a severe neonatal form of the disease. Given the difficult management of NKH caused by GLDC deletion, it was decided to adopt a preventative approach in a family with a history of this disease by using preimplantation genetic diagnosis (PGD). In this family, there is a deletion in the 5′ UTR (untranslated region) up to the third intron of GLDC . PGD was carried out using multiple displacement amplification (MDA) and fluorescent polymerase chain reaction (PCR). This resulted in a singleton pregnancy after transfer of three unaffected embryos. Post-natal DNA testing of the newborn confirmed the PGD result. This is the first report of a successful PGD cycle intended to prevent the occurrence of NKH in a family with a history of the disease. The use of MDA coupled with fluorescent PCR is a very encouraging strategy leading to both low allele drop-out (2/40) and failure of amplification (0/40) rates.