They are generally genetic defects (inborn errors of metabolism) that interfere with the ability to create energy, causing a low ATP reservoir within the muscle cell.

The main categories of metabolic myopathies are listed below:[5] In the event more ATP is needed from the affected pathway, the lack of it becomes an issue and symptoms develop.

[1][20] At the cellular level, metabolic myopathies lack some kind of enzyme or transport protein that prevents the chemical reactions necessary to create adenosine triphosphate (ATP).

Some people with a metabolic myopathy never develop symptoms due to the body's ability to produce enough ATP through alternative pathways (e.g. the majority of those with AMP-deaminase deficiency are asymptomatic[1][21]).

As genetic sequencing research progresses, a non-invasive neuromuscular panel DNA test can help make a diagnosis.

[7][9] A 12 Minutes Walk Test (12MWT) can also be used to determine "second wind" which is also seen in McArdle disease (GSD-V) and phosphoglucomutase deficiency (PGM1-CDG/CDG1T/GSD-XIV).

[34] Glycogen storage diseases may show transient exercise-induced alkalosis (high pH), hyperammonemia, and myogenic hyperuricemia.

[2] Some fatty acid oxidation disorders show lactic acidosis, hypoketotic hypoglycaemia and hyperammonemia, while others are asymptomatic.

[7][18] Those with muscle glycogenoses can maintain a healthy life of exercise by learning activity adaptations, utilizing the bioenergetic systems that are available to them.

Depending on the type of activity and whether they are in second wind, they slow their pace or rest briefly when need be, to make sure not to empty their "ATP reservoir.

[11][47][43][48] Once a correct diagnosis has been made, in adult years, looking back symptoms were present since childhood, but either brushed-off as growing pains, laziness, or told that they just needed to exercise more.

[11][20][43] Sitting in a doctor's office (at rest) or doing movements that only last a few seconds (within the time limit of the phosphagen system) the patient wouldn't display any noticeable abnormalities (such as muscle fatigue, cramping, or breathlessness).

In the absence of severe symptoms (such as hepatomegaly, cardiomyopathy, hypoglycemia, lactic acidosis, myoglobinuria, rhabdomyolysis, acute compartment syndrome or renal failure), it is understandable that a disease would not be noticed by medical professionals for years, when at rest the patient appears completely normal.

[citation needed] Depending on what enzyme is affected, a high-protein or low-fat diet may be recommended along with mild exercise.

[52][43] For the regularly active patients, it took more strenuous exercise (very brisk walking/jogging or bicycling) for them to experience both the typical symptoms and relief thereof, along with the sign of an increased heart rate dropping, demonstrating second wind.