Biochemical and molecular basis for mitochondrial cardiomyopathy in neonates and children

Abstract

Defects in myocardial bioenergetics have been reported in patients with cardiomyopathy but their molecular basis and role in pathophysiology remain unclear. We sought to establish a molecular basis for cardiac mitochondrial respiratory enzyme abnormalities frequently present (75%) in a group of 16 children (including 2 neonates) with end-stage cardiomyopathy. Decreased specific activity levels were found in complexes I, III, IV and V but not in II, the only complex that is entirely nuclear encoded. Sequence analysis of cardiac mtDNA revealed 4 patients harbouring heteroplasmic mtDNA mutations in cytb, tRNAArg, and ND5 at highly conserved positions. These mutations were present neither in controls nor in patients without enzymatic defect. In addition, 4 patients exhibited marked reduction in cardiac mtDNA levels. The basis for respiratory enzyme abnormalities can be explained in a subset of our patients as a result of either pathogenic mtDNA mutation or depletion. Patients harbouring both DNA and enzymatic defects fulfil rigorous criteria defining mitochondrial cardiomyopathy.

DOI: 10.1023/A:1005638231195

3 Figures and Tables

Statistics

050100150'03'05'07'09'11'13'15'17
Citations per Year

228 Citations

Semantic Scholar estimates that this publication has 228 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{MarnGarca2000BiochemicalAM, title={Biochemical and molecular basis for mitochondrial cardiomyopathy in neonates and children}, author={Jos{\'e} Mar{\'i}n-Garc{\'i}a and Radha Ananthakrishnan and Michael J. Goldenthal and Mary Ella Pierpont}, journal={Journal of Inherited Metabolic Disease}, year={2000}, volume={23}, pages={625-633} }