Mitochondrial Encephalomyopathy: Know Your TCA Cycle?

Two reports expand our understanding of mitochondrial disease associated with nuclear DNA mutations — but questions remain as to the mechanism.

The mitochondrial genome (mtDNA) encodes the genes for the mitochondrial respiratory chain. Mutations in mtDNA are well-recognized causes of human diseases, usually inherited through maternal lineage, that often affect the skeletal muscle and nervous system. However, mutations of nuclear DNA (nDNA) are increasingly recognized as causes of mitochondrial diseases because some nDNA genes code for proteins that affect the stability of mtDNA. A report in 2005 first described homozygous mutations in the SUCLA2 gene in a small consanguineous Israeli-Muslim family with mitochondrial encephalomyopathy associated with combined complex I, III, and IV deficiency and mtDNA depletion in muscle. The clinical features were suggestive of Leigh syndrome.

Two …

Reviewing Author

Edward H. Koo, MD