RESUMO
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.
