A high rate (20%-30%) of parental consanguinity in cytochrome-oxidase deficiency.
By studying a large series of 157 patients, we found that complex I (33%), complex IV (28%), and complex I+IV (28%) deficiencies were the most common causes of respiratory chain (RC) defects in childhood. Truncal hypotonia (36%), antenatal (20%) and postnatal (31%) growth retardation, cardiomyopathy (24%), encephalopathy (20%), and liver failure (20%) were the main clinical features in our series. No correlation between the type of RC defect and the clinical presentation was noted, but complex I and complex I+IV deficiencies were significantly more frequent in cases of cardiomyopathy (P<.01) and hepatic failure (P<.05), respectively. The sex ratio (male/female) in our entire series was mostly balanced but was skewed toward males being affected with complex I deficiency (sex ratio R=1.68). Interestingly, a high rate of parental consanguinity was observed in complex IV (20%) and complex I+IV (28%) deficiencies. When parental consanguinity was related to geographic origin, an even higher rate of inbreeding was observed in North African families (76%, P<.01). This study gives strong support to the view that an autosomal recessive mode of inheritance is involved in most cases of mitochondrial disorders in childhood, a feature that is particularly relevant to genetic counseling for this devastating condition.
von Kleist-Retzow
J C
JC
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Paris, France.
Cormier-Daire
V
V
de Lonlay
P
P
Parfait
B
B
Chretien
D
D
Rustin
P
P
Feingold
J
J
Rötig
A
A
Munnich
A
A
D000015:Abnormalities, Multiple / Q000201:enzymology / Q000235:genetics*; D002648:Child; D003241:Consanguinity; D030401:Cytochrome-c Oxidase Deficiency; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000172:deficiency / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D006801:Humans; D008297:Male; D009097:Multienzyme Complexes / Q000172:deficiency / Q000235:genetics*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency / Q000235:genetics*; D009679:Nuclear Family; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D013385:Succinate Dehydrogenase / Q000172:deficiency / Q000235:genetics*
D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III