Prenatal diagnosis of non‐ketotic hyperglycinaemia: enzymatic diagnosis in 28 families and DNA diagnosis detecting prevalent Finnish and Israeli–Arab mutations

Prenatal diagnosis for non-ketotic hyperglycinaemia (NKH) was performed by enzymatic analysis of chorionic villus samples in 28 families and by DNA analysis in two families. In 26 families, enzymatic analysis of the glycine cleavage multi-enzyme system (GCS) yielded an unambiguous diagnosis; inconclusive results in two families were due to borderline GCS activitiy. We analysed a second chorionic sample in these two families. In one case, GCS activity was normal in the second specimen, and the baby did not have NKH. In the other case, we again found extremely low GCS activity in the second specimen, but a healthy baby was born. The cause of this false-positive result is unknown. Molecular analysis of NKH has identified two prevalent mutations to date; the S564I mutation in a gene encoding the P-protein, a component of the GCS, in a Finnish population, and the H42R mutation in a gene encoding the T-protein in the Israeli–Arab population. These prevalent mutations allow us to obtain unambiguous prenatal diagnoses in both Finnish and Israeli–Arab families. GCS activity in samples from a Finnish family demonstrated a good agreement with DNA analysis, but the fetus of the Israeli–Arab family had an upper limit activity of the affected range, suggesting an advantages for DNA analysis. Copyright © 1999 John Wiley & Sons, Ltd.