title: Prenatal diagnosis of NADH:ubiquinone oxidoreductase deficiency.
abstract: NADH:ubiquinone oxidoreductase (complex I of the mitochondrial respiratory chain) deficiency is a severe disorder with an often early fatal outcome. Prenatal diagnosis for complex I defects currently relies mainly on biochemical assays of complex I in fetal tissues such as chorionic villi (CV), and is only in a minority of cases possible by means of mutational analysis of nuclear-encoded genes of complex I. We report on our experience to date with prenatal diagnosis in pregnancies at risk for complex I deficiency. We measured complex I activity in native CV and/or cultured CV in 23 pregnancies in 15 families. In accordance with the results of the investigations in CV, 15 children were born clinically unaffected. Two prenatally diagnosed unaffected fetuses and two prenatally diagnosed affected fetuses were lost prematurely with spontaneous or provoked abortions, respectively. Two affected children were born (prenatally found to be affected). In two pregnancies a discrepancy between native and cultured cells was found. We conclude that prenatal diagnosis for complex I deficiency can be reliably performed. Pitfalls were encountered in using cultured CV as a result of maternal cell contamination (MCC). Future research on pathogenic nuclear mutations underlying complex I deficiency will extend the possibilities for prenatal diagnosis at the molecular level.
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors.forename: L E
authors.initials: LE
authors.lastname: Niers
authors.forename: J A
authors.initials: JA
authors.lastname: Smeitink
authors.forename: J M
authors.initials: JM
authors.lastname: Trijbels
authors.forename: R C
authors.initials: RC
authors.lastname: Sengers
authors.forename: A J
authors.initials: AJ
authors.lastname: Janssen
authors.forename: L P
authors.initials: LP
authors.lastname: van den Heuvel
mesh_terms: D001706:Biopsy; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000201:enzymology; D042967:Electron Transport Complex I; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005865:Gestational Age; D006801:Humans; D018482:Muscle, Skeletal / Q000201:enzymology; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency* / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome; D011296:Prenatal Diagnosis / Q000379:methods*; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I