Mitochondrial cytopathies represent a heterogenous group of disorders with abnormal mitochondrial structure or function as the defining entity and with clinical onset across all age groups. Given that the mitochondria provide the majority of cellular adenosine 5′-triphosphate (ATP), the clinical symptoms can manifest with a myriad of presentations. Cellular pathology includes a reduction in aerobic energy transduction, an increase in anaerobic energy utilization (lactate production), and, in some cases, higher oxidative stress. Diagnostic criteria include history (classic multisystem involvement), blood test abnormalities (elevated lactate, alanine, and creatine kinase activity), urine organic acids (3-methylglutaconic acid, ethylmalonic acid, fumarate), muscle enzymology (reduction in activity), exercise testing (low maximum oxygen consumption [V˙O2max], early lactate production) and other ancillary tests, including MRI, MR spectroscopy, and near-infrared spectroscopy. Treatment is multifactorial and supportive, including optimization of nutrition and deficiency (folate and vitamin B12) replacement, gastrostomy tube if necessary (failure to thrive), treatment of secondary neurologic issues, vitamin and cofactor therapy (creatine monohydrate, coenzyme Q10, α-lipoic acid, etc), and exercise.
Relationship Disclosure: Dr Tarnopolsky has received personal compensation for speaking engagements with Transgenomic, Inc., has received personal compensation in an editorial capacity from Medicine & Science in Sports & Exercise, and has received research support from ApoPharma, Inc., and Gilead.
Unlabeled Use of Products/Investigational Use Disclosure: Dr Tarnopolsky has nothing to disclose.