Mitochondrial myopathies are disorders caused by the failure of mitochondria to generate sufficient energy for the body’s cells. Mitochondria produce the vast majority of the body’s energy supply. A myopathy is a disease that affects the muscles, leading to functional problems like weakness. This class of diseases results when mitochondrial dysfunction primarily impacts muscle tissue, though the effects often extend far beyond the muscles. This energy crisis causes a wide range of symptoms that can affect multiple organ systems, particularly those with high energy demands.
The Role of Mitochondria in Muscle Function
Mitochondria’s primary function is generating Adenosine Triphosphate (ATP), the energy used by nearly all cells. This process, known as oxidative phosphorylation, occurs within the inner mitochondrial membrane via the electron transport chain (ETC). The ETC uses oxygen to convert energy stored in food molecules into ATP.
Muscle tissue, especially skeletal and cardiac muscle, has an extremely high energy requirement, making it heavily reliant on efficient mitochondrial function. Mitochondria in muscle cells have numerous folds called cristae, enhancing their capacity for ATP production. If mitochondria cannot perform this function effectively, muscle cells become energy-starved and cannot contract properly. This explains why muscle weakness and fatigue are the hallmark symptoms of mitochondrial myopathies.
How Defects Lead to Disease
Mitochondrial myopathies are caused by genetic defects that compromise energy production. Mutations occur in either the mitochondrial DNA (mtDNA) or the nuclear DNA (nDNA). The mtDNA is a small, circular genome containing 37 genes essential for the ETC, and mutations are inherited exclusively from the mother.
The majority of proteins required for mitochondrial function are encoded by genes located in the nDNA, which is inherited from both parents. The severity of an mtDNA mutation depends on heteroplasmy, where a cell contains a mixture of normal and mutated mitochondrial DNA copies. A threshold of mutated mtDNA must be reached before the energy deficit causes symptoms, accounting for wide variation in disease presentation among individuals.
Recognizing the Signs
Mitochondrial myopathies range from muscle-limited issues to severe multi-system disorders. Primary symptoms include progressive skeletal muscle weakness, particularly in proximal muscles like the hips and shoulders. This weakness often manifests as exercise intolerance, where physical activity quickly leads to profound fatigue and muscle pain.
Since mitochondria are present in nearly every cell, energy failure often affects other high-energy organs, leading to multi-systemic disease. Neurological problems are frequent, including seizures, ataxia, and stroke-like episodes. Cardiac involvement commonly presents as cardiomyopathy or conduction defects such as arrhythmias. Other signs include sensorineural hearing loss and visual impairment involving the optic nerve or retina. The combination of multiple, seemingly unrelated symptoms across different organ systems is a strong clinical indicator.
Confirming a Diagnosis
Diagnosis requires a combination of clinical assessment and specific laboratory tests. Blood tests often reveal metabolic abnormalities, such as elevated lactate and pyruvate levels, especially after exercise, indicating reliance on less efficient energy pathways. These findings alone are not definitive.
A muscle biopsy involves analyzing a small sample of muscle tissue under a microscope. A characteristic finding is “ragged red fibers” (RRFs), which are muscle cells containing abnormal accumulations of mitochondria. Histochemical staining can also detect a deficiency in specific electron transport chain enzymes, such as cytochrome c oxidase (COX). Genetic testing provides definitive confirmation by sequencing mitochondrial and nuclear DNA to identify the specific mutation.
Treatment and Supportive Care
There is no cure for mitochondrial myopathies, and treatment focuses on supportive care and managing symptoms to maintain quality of life. A multidisciplinary approach involving specialists in neurology, cardiology, and physical therapy is necessary to address the diverse affected systems. Regular physical and occupational therapy are recommended to prevent muscle deconditioning and improve strength and endurance.
Nutritional support often includes dietary supplements aimed at enhancing mitochondrial function. Coenzyme Q10 (CoQ10), an electron carrier in the ETC, is a common supplement, especially for patients with a primary CoQ10 deficiency. Other supplements are often recommended to optimize metabolic pathways, including:
- L-carnitine
- L-arginine
- B vitamins like riboflavin
Patients are also advised to avoid fasting and certain medications that could inhibit the compromised respiratory chain.