Mitochondrial dysfunction in skeletal muscle of children with cardiomyopathy

Objectives. This study sought to examine skeletal muscle of children with c ardiomyopathy (CM) for changes in mitochondrial enzyme activities and in mi tochondrial DNA (mtDNA). Background. Heart mitochondrial enzymatic activity defects have been often found in dilated and hypertrophic CM. The defects primarily involve the act ivities of the electron transport system and oxidative phosphorylation path way including respiratory complexes I, III, IV, and V. Methods, Skeletal muscle biopsies of 8 children with CM were examined for s pecific mitochondrial enzyme activities, mtDNA copy number and the presence of pathogenic mutations and deletions in mtDNA. Results. A marked deficiency in specific mitochondrial enzyme activities wa s found in 6 of 8 patients in skeletal muscle as well as in 2 of 3 hearts o f those in whom cardiac tissue was available. Specific activity defects wer e found in complex I (2 cases), complex III (5 cases), complex IV (3 cases) , and complex V (4 cases). Complex II and citrate synthase activities were unaffected, None of the previously reported pathogenic mutations associated with CM were detected, nor was there any evidence of mtDNA depletion. The incidence of defective respiratory complex activities in skeletal muscle wa s similar to the incidence of defective complex activities previously repor ted in cardiac tissue. Conclusions, Mitochondrial analysis of skeletal muscle is warranted in the overall clinical evaluation of children with CM, and particularly before co nsideration for cardiac transplantation.