Mitochondrial Encephalomyopathies


Mitochondrial functions:

•         cellular energy metabolism

•         cell signaling

•         apoptosis

•         intermediary metabolism

•         metabolism of AA, lipids, cholesterol, steroids and nucleotides

•         intracellular sequestration of calcium

•         detoxification of ammonia



Mitochondrial genetics:

•         circular double stranded ring of DNA

•         2 ribosomal RNAs, 22 transfers RNAs, 13 polypeptides of complexes I, III, IV, and V of the respiratory chain

•         2-10 mtDNA rings per mitochondria

•         cells contain thousands of mitochondria



Clinical testing:

•         resting serum lactate – often elevated due to increase anaerobic metabolism

•         CPK – muscle involvement

•         TSH, glucose, Hgb A1C – endocrine dysfunction

•         serum AA, urine organic acids, VLCFA, serum biotinidase – metabolic screen

•         CSF lactate – more sensitive than serum

•         ECG – cardiac involvement common

•         EEG – may show slowing

•         audiography – often have impaired hearing

•         EMG/NCS – help to localize problem to muscle

•         CT/MRI – often show atrophy and related ventriculomegaly, white matter changes, calcification (esp brain stem and BG)

•         Muscle Biopsy

•         H&E,  Succinate Dehydrogenase, Modified Gomori-Trichrome, Cytochrome C Oxidase

•         Molecular Studies (Southern Blot, PCR, biochemistry on cultured fibroblasts for respiratory complex activity)



“Common” mitochondrial encephalomyopathies:


LHON – Leber’s hereditary optic neuropathy


MELAS – Mitchondrial encephalopathy with lactic acidosis and stroke-like episodes


MERFF – Myoclonic epilepsy with ragged red fibers


Leigh syndrome


Kearns-Sayre syndrome



Management of mitochondrial disorders:





Reference: Taylor RW & Turnbull DM. (2005). Mitochondrial DNA mutations in human disease. Nature Rev Gen. 6:389-402.