Mitochondrial myopathy

Definitions & Key takeaways

Mitochondrial myopathies refers to a group of neuromuscular disorders caused by damage to the mitochondria, which are the energy-producing organelles in cells. This damage can disrupt the normal function of muscles and organs. Symptoms may include body weakness, exercise intolerance, loss of muscle mass, and problems with breathing, seizures, ophthalmoplegia (paralysis of eye muscles), and hypotonia (abnormally reduced muscle tone).

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Primary mitochondrial myopathy is a rare genetic disorder that occurs when there are mutated mitochondria in muscle cells, especially skeletal muscle cells.
These mitochondria are unable to generate adenosine triphosphate or ATP, which is a form of energy used by our cells. As a result, muscle cells which require a lot of energy to function, stop functioning properly.
The mitochondria are the main energy producing factories of a cell and they do so with the help of the electron transport chain and the enzyme ATP synthase, the electron transport chain is made up of complexes of proteins or lipids called electron carriers embedded within the inner mitochondrial membrane which pass electrons along like the baton in a relay race.
This movement of electrons helps establish a proton gradient that drives ATP synthase to phosphorylate adenosine diphosphate or ADP into ATP.
Primary mitochondrial myopathy is caused by a mutation either in the mitochondrial DNA or nuclear DNA, which results in the abnormal production of mitochondrial proteins.
Impairing the function of the electron transport chain. Mutations in the nuclear DNA are commonly inherited in an autosomal dominant fashion which means one mutated gene is enough to cause the disease or autosomal recessive fashion, which means two mutated genes, one from each parent are needed to cause the disease.
Mutations in the mitochondrial DNA follow maternal inheritance, meaning that only an affected woman can pass on the disease to her Children.
This is because typically during fertilization, the father's mitochondria are left behind while the sperm's nucleus alone enters the egg.
The exception is the mitochondrial DNA single deletion. A common cause of primary mitochondrial myopathy, which is always sporadic and cannot be transmitted to the offspring.
In primary mitochondrial myopathy, muscle cells are unable to generate ATP which results in muscle weakness and fatigue.
Sometimes there may also be muscle pain, cramping, stiffness or even paralysis of the muscle. Individuals typically develop exercise intolerance which is a reduced ability to perform physical activity.
Symptoms vary based on the group of muscles affected in most individuals. The first to be affected are the extraocular muscles which control eye movements which results in progressive external ophthalmoplegia.
Symptoms of progressive external ophthalmoplegia include restricted eye movements, diplopia or double vision and ptosis or drooping of eyelids.
Facial muscle involvement can cause slurred speech and swallowing, difficulty, involvement of chest wall muscles results in respiratory failure, involvement of muscles in the hands and legs can affect day to day activities like walking, eating and riding.
Diagnosis begins with a physical and neurological examination to rule out central nervous system involvement. A muscle biopsy is the gold standard test.
It shows the characteristic ragged red fibers which are caused by compensatory proliferation of abnormal mitochondria. In addition, biochemical tests can be done to look for elevated blood lactate levels.
High blood lactate to pyruvate ratio and elevated serum creatinine kinase. And genetic testing can be done to look for mutations in mitochondrial or nuclear DNA.
While there is no cure for primary mitochondrial myopathy, there are treatment options, supportive care can be given to help manage symptoms.
In addition, individuals may require regular exercise to improve muscle function supplements called mitochondrial cocktails or mito cocktails containing vitamins, creatine antioxidants and coenzyme Q 10, which is a component of the electron transport chain can be given to improve mitochondrial activity.
All right. As a quick recap, primary mitochondrial myopathy is a genetic disorder caused by mutations in the mitochondrial or nuclear DNA, which results in the inability of muscle cells to produce enough ATP common symptoms include restricted eye movements, diplopia, ptosis, slurred, speech, swallowing, difficulty, muscle weakness, and wasting and respiratory failure.
Diagnosis is made with the help of a muscle biopsy. Biochemical tests for blood lactate levels, lactate to pyruvate ratio and creatinine levels and genetic tests to detect mutations in the DNA.
While there is currently no cure. Treatment includes symptomatic management, regular exercise and mitochondrial cocktail supplements.