Non-concordance of CVS and liver glycine cleavage enzyme in three familieswith non-ketotic hyperglycinaemia (NKH) leading to false negative prenataldiagnoses

We report three false negative prenatal diagnostic results, using direct me asurement of glycine cleavage enzyme activity in uncultured chorionic villu s tissue from 290 pregnancies at risk for non-ketotic hyperglycinaemia (NKH ). Testing was done by two centres: Vancouver, Canada and Lyon, France. One false negative result had activity near the lower limit of the normal rang e but two samples gave completely normal results well within the control ra nge. All three pregnancies continued and the three children were born affec ted with NKH. Because of the first result, we now counsel that there is a g rey zone of uninterpretable activity where affected and normal enzyme value s overlap. Because of the other two results we now counsel that there is an approximately 1% chance of a pregnancy with a normal CVS activity resultin g in an affected child. The clinical and biochemical findings in the three families are discussed. Copyright (C) 2000 John Wiley & Sons, Ltd.