Prenatal Diagnosis in Families with Impaired Activityof Cytochrome c Oxidase

Overview

Objective:
Cytochrome c oxidase (COX) deficiency presents with severe impairment of brain,muscle or heart. Prenatal diagnosis in affected families is difficult because the disease may be caused by mutations in nuclear or mtDNA. This study shows the results of prenatal diagnosis intwo families where the first child died because of a generalised COX defect. In both cases the lowactivity of COX was accompanied by a low content of the enzyme.Subjects: In the first family the amniocentesis was performed during the second pregnancy andcultured amniocytes showed a marked decrease of COX activity and ATP production. Based ondecision of the parents the pregnancy was terminated. Analysis of the foetal tissues confirmeda generalised COX defect. In the second family the nuclear origin of the COX defect was foundusing transmitochondrial cybrids derived from COX-deficient fibroblasts of the affected child. Inthe successive pregnancy with dizygotic twins a combined amniocentesis and chorionic villi bio-psy has been performed. Prenatal diagnosis was based in both foetuses on three independentapproaches. COX activity, the ATP production and protein content of COX complex was measuredin cultivated foetal cells. The results of all investigations excluded a putative COX defect and bothchildren are healthy at the age of 2 and half years.Conclusion: Prenatal diagnosis of COX disorders is available in families with the generalised formof the disease based on a nuclear origin of COX deficiency. Three independent approaches tocharacterise COX at a functional, enzymatic and protein level may be used.

Key words:
cytochrome c oxidase, transmitochondrial cybrids, mtDNA