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Mitochondrial dysfunction in skeletal muscle of children with cardiomyopathy
J Marin-Garcia1, R Ananthakrishnan, M J Goldenthal
1The Molecular Cardiology Institute, Highland Park, New Jersey 08904, USA.
Insights
Skeletal muscle mitochondrial enzyme defects are common in children with cardiomyopathy (CM). These findings suggest skeletal muscle analysis is important for evaluating pediatric CM patients, especially before heart transplantation.
Area of Science:
- Pediatric Cardiology
- Mitochondrial Medicine
- Skeletal Muscle Physiology
Background:
- Mitochondrial enzymatic activity defects are frequently observed in pediatric cardiomyopathy.
- Defects often impact the electron transport system and oxidative phosphorylation, including respiratory complexes I, III, IV, and V.
Purpose of the Study:
- To investigate mitochondrial enzyme activities and mitochondrial DNA (mtDNA) in the skeletal muscle of children diagnosed with cardiomyopathy.
- To identify potential diagnostic markers and therapeutic targets in pediatric CM.
Main Methods:
- Analysis of skeletal muscle biopsies from 8 children with cardiomyopathy.
- Assessed specific mitochondrial enzyme activities, mtDNA copy number, and screened for pathogenic mtDNA mutations and deletions.
Main Results:
- Significant deficiencies in specific mitochondrial enzyme activities were identified in the skeletal muscle of 6 out of 8 patients.
- Defects were noted in respiratory complexes I, III, IV, and V, with no abnormalities in complex II or citrate synthase.
- No previously reported pathogenic mtDNA mutations or evidence of mtDNA depletion were found.
Conclusions:
- Mitochondrial analysis of skeletal muscle is a valuable component of the clinical evaluation for children with cardiomyopathy.
- These findings support considering skeletal muscle biopsy in the diagnostic workup, particularly prior to cardiac transplantation evaluation.
Objectives:
This study sought to examine skeletal muscle of children with cardiomyopathy (CM) for changes in mitochondrial enzyme activities and in mitochondrial DNA (mtDNA).
Background:
Heart mitochondrial enzymatic activity defects have been often found in dilated and hypertrophic CM. The defects primarily involve the activities of the electron transport system and oxidative phosphorylation pathway including respiratory complexes I, III, IV, and V.
Methods:
Skeletal muscle biopsies of 8 children with CM were examined for specific 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 was found in 6 of 8 patients in skeletal muscle as well as in 2 of 3 hearts of those in whom cardiac tissue was available. Specific activity defects were 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 was similar to the incidence of defective complex activities previously reported in cardiac tissue.
Conclusions:
Mitochondrial analysis of skeletal muscle is warranted in the overall clinical evaluation of children with CM, and particularly before consideration for cardiac transplantation.