[1] Adenosine triphosphate (ATP), the chemical used to provide energy for the cell, cannot be produced sufficiently by oxidative phosphorylation when the mitochondrion is either damaged or missing necessary enzymes or transport proteins.

With ATP production deficient in mitochondria, there is an over-reliance on anaerobic glycolysis which leads to lactic acidosis either at rest or exercise-induced.

[6][8] Some mitochondrial myopathies are limited to disease expression only in skeletal muscle, with fibroblasts (from skin biopsy) appearing normal.

[6][2] Electrolyte panel, anion gap, glucose, vitamin D, TSH, anti-HMGCR and AChR autoantibodies to rule-out pseudometabolic myopathies.

[6][8] Even among siblings with the same inherited mutation, different muscle groups were affected, with unaffected tissues having near normal levels of mtDNA.

[6] DNA testing is helpful for determining between the similar presenting, but different in bioenergetic system origin, metabolic myopathies.

If symptoms of muscle fatigue improve after approximately 10 minutes of low-moderate intensity aerobic exercise, or after approximately 10 minutes of rest following aerobic exercise, this would be indicative of the second wind phenomenon seen in select muscle glycogenoses.

However, it is important to note as a differential diagnosis as not only do the symptoms overlap with mitochondrial myopathies, but also muscle biopsies of some individuals with MADD show COX-negative fibres, respiratory chain impairment, and deficiency of coenzyme Q10.

[62] Myopathies involving the DMD gene, such as Duchenne and Becker muscular dystrophy, have secondary mitochondrial dysfunction impairing oxidative phosphorylation.

[3] Three unrelated young boys, with a mutation in the DMD gene, exhibited a pseudometabolic presentation with symptoms of exercise intolerance manifesting as exercise-induced myalgia, muscle stiffness, myoglobinuria and rhabdomyolysis.

[63][66] MICU1-related myopathy with extrapyramidal signs has disrupted calcium uptake causing secondary mitochondrial dysfunction.

Deoxynucleoside monophosphates and deoxynucleotide taken orally, may help in TK2 deficiency (Mitochondrial DNA depletion syndrome 2 myopathic type).

[6] Avoiding physically stressful situations that deplete glycogen reserves, such as fasting and endurance exercise (which rely predominantly on oxidative phosphorylation), may help.