Cytochrome c oxidase (
COX) deficiency has been associated with a wide spectrum of clinical features and may be caused by mutations in different genes of both the mitochondrial and the nuclear
DNA. In an attempt to correlate the clinical phenotype with the genotype in 16 childhood cases,
mtDNA was analysed for deletion, depletion, and mutations in the three genes encoding COX subunits and the 22
tRNA genes. Furthermore, nuclear
DNA was analysed for mutations in the SURF1, SCO2, COX10, and COX17 genes and cases with
mtDNA depletion were analysed for mutations in the TK2 gene. SURF1-mutations were identified in three out of four cases with
Leigh syndrome while a mutation in the mitochondrial
tRNA (trp) gene was identified in the fourth. One case with
mtDNA depletion had mutations in the TK2 gene. In two cases with
leukoencephalopathy, one case with
encephalopathy, five cases with fatal infantile
myopathy and
cardiomyopathy, two cases with benign infantile
myopathy, and one case with
mtDNA depletion, no mutations were identified. We conclude that
COX deficiency in childhood should be suspected in a wide range of clinical settings and although an increasing number of genetic defects have been identified, the underlying mutations remain unclear in the majority of the cases.