Determination of enzyme activities for prenatal diagnosis of respiratory chain deficiency

Genetic counselling and prenatal diagnosis are major issues of mitochondria l respiratory chain deficiency, especially as these conditions are largely untreatable. In the absence of known mitochondrial or nuclear gene mutation s, measurement of respiratory chain enzyme activities represents the only p ossibility to prevent recurrence of the disease in affected families. We ca rried out enzymatic prenatal diagnosis in 21 pregnancies from 10 unrelated couples using uncultured choriocytes and/or amniocytes. Twelve babies were born and are healthy, seven pregnancies were discontinued early on because of an enzyme deficiency detected prenatally. In two cases, a fetus which ap peared normal after early and/or late prenatal diagnosis, turned out to be affected. We conclude that a deficient enzyme activity is indicative of rec urrence, but a normal result at 10 weeks of gestation does not give conclus ive evidence as to the outcome of the pregnancy. We therefore suggest the f ollowing procedure: (1) a choriocentesis or an amniocentesis in early pregn ancy when the proband expresses the disease in cultured skin fibroblasts; ( 2) a second amniocentesis at 28 weeks' gestation should be offered to avoid false negative results due to a possible late expression of the disease, i n combination with: (3) a careful and repeated ultrasound survey for detect ion of growth failure in the third trimester; (4) prenatal diagnosis should not be performed in case of late onset clinical symptoms in the proband; a nd (5) parents should be aware of the possibility of false negative results . Prenatal diagnosis should not be proposed for a complex I deficiency as t his enzyme activity cannot be accurately measured in fetal cells. Copyright (C) 2000 John Wiley & Sons, Ltd.