title: Determination of enzyme activities for prenatal diagnosis of respiratory chain deficiency.
abstract: Genetic counselling and prenatal diagnosis are major issues of mitochondrial respiratory chain deficiency, especially as these conditions are largely untreatable. In the absence of known mitochondrial or nuclear gene mutations, measurement of respiratory chain enzyme activities represents the only possibility to prevent recurrence of the disease in affected families. We carried 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 appeared normal after early and/or late prenatal diagnosis, turned out to be affected. We conclude that a deficient enzyme activity is indicative of recurrence, but a normal result at 10 weeks of gestation does not give conclusive evidence as to the outcome of the pregnancy. We therefore suggest the following procedure: (1) a choriocentesis or an amniocentesis in early pregnancy 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, in combination with: (3) a careful and repeated ultrasound survey for detection of growth failure in the third trimester; (4) prenatal diagnosis should not be performed in case of late onset clinical symptoms in the proband; and (5) parents should be aware of the possibility of false negative results. Prenatal diagnosis should not be proposed for a complex I deficiency as this enzyme activity cannot be accurately measured in fetal cells.
authors.affiliation: Unité de Recherche sur les Handicaps Génétiques de l'Enfant, INSERM U-393 and Département de Génétique, Hôpital Necker Enfants-Malades, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Faivre
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: D
authors.initials: D
authors.lastname: Chrétien
authors.forename: J
authors.initials: J
authors.lastname: Christoph von Kleist-Retzow
authors.forename: J
authors.initials: J
authors.lastname: Amiel
authors.forename: M
authors.initials: M
authors.lastname: Dommergues
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: Y
authors.initials: Y
authors.lastname: Dumez
authors.forename: A
authors.initials: A
authors.lastname: Rötig
authors.forename: P
authors.initials: P
authors.lastname: Rustin
authors.forename: A
authors.initials: A
authors.lastname: Munnich
mesh_terms: D000328:Adult; D000649:Amniocentesis; D015193:Chorionic Villi Sampling; D003241:Consanguinity; D004579:Electron Transport; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000201:enzymology*; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D017240:Mitochondrial Myopathies / Q000175:diagnosis / Q000201:enzymology*; D009249:NADP / Q000172:deficiency / Q000378:metabolism*; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012867:Skin / Q000166:cytology / Q000201:enzymology
chemical_list: D009249:NADP