Mitochondrial myopathy is a group of disorders caused by dysfunctional mitochondria, leading to impaired muscle function. These tiny structures, often called the “powerhouses” of cells, generate most of the chemical energy needed for cellular processes. When they do not function correctly, cells—especially muscle cells with high energy demands—cannot produce enough energy, resulting in muscle weakness and fatigue.
Understanding Mitochondrial Myopathy
Mitochondria are double-membraned organelles located within the cytoplasm of eukaryotic cells. Their primary function is to generate adenosine triphosphate (ATP), the cell’s main energy currency, through a process called oxidative phosphorylation (OXPHOS). Muscle cells, along with brain, heart, and kidney cells, contain a large number of mitochondria due to their high energy requirements.
When mitochondria are dysfunctional, this energy production is impaired, leading to a deficit in ATP, especially in skeletal muscle. This energy shortage prevents muscle cells from functioning properly, resulting in muscle weakness, fatigue, and exercise intolerance seen in mitochondrial myopathy. Mitochondrial myopathies are genetic disorders, arising from mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA), both of which control mitochondrial function. While mtDNA is inherited solely from the mother, nDNA mutations follow Mendelian inheritance patterns.
Different Forms of Mitochondrial Myopathy
Mitochondrial myopathy manifests in various forms, each with distinct symptoms and affected body systems. These conditions are often progressive, meaning symptoms worsen over time.
MELAS Syndrome
MELAS, an acronym for Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes, affects the nervous system and muscles. Symptoms appear in childhood or adolescence, though onset can occur at any age. Early signs can include muscle weakness and pain, recurrent headaches, and vomiting. A hallmark of MELAS is the occurrence of stroke-like episodes, which can cause temporary muscle weakness, altered consciousness, vision abnormalities, and seizures. Repeated stroke-like episodes can lead to progressive brain damage, resulting in vision loss, movement problems, and intellectual decline.
Individuals with MELAS experience a buildup of lactic acid in the body, known as lactic acidosis, which contributes to fatigue, muscle weakness, and breathing difficulties. Other frequent complications include hearing loss, diabetes, and issues with gait and balance. Mutations in genes like MT-TL1 are a common cause.
MERRF Syndrome
MERRF, or Myoclonic Epilepsy with Ragged-Red Fibers, is a rare mitochondrial disease affecting multiple body parts, particularly the muscles and nervous system. Symptoms emerge during childhood or adolescence. The most distinguishing feature is myoclonus, characterized by sudden, brief, jerking muscle spasms that can affect limbs or the entire body.
Individuals with MERRF also experience seizures, difficulty coordinating movements (ataxia), and progressive muscle weakness. A muscle biopsy reveals “ragged-red fibers,” which are muscle cells with an abnormal appearance due to dysfunctional mitochondria. Other potential symptoms include dementia, optic atrophy, bilateral deafness, peripheral neuropathy, and heart abnormalities such as cardiomyopathy. The clinical presentation varies widely among affected individuals.
Kearns-Sayre Syndrome (KSS)
Kearns-Sayre Syndrome (KSS) is a mitochondrial myopathy that presents before 20 years of age. It is characterized by a specific triad of symptoms: progressive external ophthalmoplegia, pigmentary retinopathy, and cardiac conduction defects. Progressive external ophthalmoplegia involves weakness or paralysis of the eye muscles, leading to drooping eyelids (ptosis) and impaired eye movement. This causes individuals to tilt their head to see.
Pigmentary retinopathy is a degeneration of the light-sensing tissue at the back of the eye (retina), causing a speckled appearance and potentially vision loss. Cardiac conduction defects can lead to abnormal heart rhythms and sometimes require a pacemaker. Other symptoms that may accompany KSS include limb muscle weakness, deafness, kidney problems, and a decline in cognitive function. KSS is associated with large-scale deletions in mitochondrial DNA.
Chronic Progressive External Ophthalmoplegia (CPEO)
Chronic Progressive External Ophthalmoplegia (CPEO) is a disorder characterized by the slow, progressive paralysis of the extraocular muscles, which control eye movement. This leads to drooping eyelids (ptosis) and limited eye movements, requiring individuals to turn their head to look in different directions. CPEO can begin at any age, manifesting in young adulthood, and progresses over several years.
While it can be an isolated condition, CPEO may also occur as part of a broader mitochondrial disease, such as Kearns-Sayre Syndrome. Some individuals with CPEO may also experience muscle weakness in the arms and legs, difficulty swallowing (dysphagia), and hearing loss. Genetic mutations, including deletions in mitochondrial DNA, are common causes of CPEO, though some cases arise spontaneously.
Identifying Mitochondrial Myopathy
Diagnosing mitochondrial myopathy involves a comprehensive evaluation, starting with a review of a patient’s physical symptoms and family medical history. A thorough clinical assessment, considering the wide range of symptoms and affected organs, is the initial step to guide further investigations.
Various diagnostic tests are used to confirm the presence of mitochondrial myopathy. Blood tests can measure levels of lactate and pyruvate, which may be elevated due to impaired energy metabolism. A muscle biopsy is a standard test, where a small sample of muscle tissue is examined under a microscope. This can reveal “ragged-red fibers,” an abnormal appearance due to dysfunctional mitochondria.
Genetic testing is increasingly used as a primary diagnostic tool to identify mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Techniques like next-generation sequencing (NGS) can detect a wide range of genetic changes. Imaging studies, such as MRI scans of the brain or muscle tissue, can also provide visual evidence of disease impact.
Living With Mitochondrial Myopathy
There is currently no cure for mitochondrial myopathy, so management focuses on alleviating symptoms and improving a patient’s overall quality of life. Treatment plans are individualized, considering the specific symptoms and organs affected. A multidisciplinary care team, including neurologists, cardiologists, dieticians, and therapists, often addresses the varied manifestations of the condition.
Physical therapy can help maintain muscle strength and mobility, while occupational therapy assists with daily activities. Speech therapy may be beneficial for individuals experiencing slurred speech or difficulty swallowing due to muscle weakness. For cardiac issues, a cardiologist monitors heart function, and in some cases, a pacemaker may be necessary to manage abnormal heart rhythms.
Nutritional support and supplements are used, though their efficacy varies. Coenzyme Q10 (CoQ10), L-carnitine, and riboflavin are commonly used, sometimes in combination. CoQ10, an antioxidant and component of the electron transport chain, has shown promise in some individuals. Exercise training, including aerobic or resistance exercises, can also improve strength and reduce fatigue in some patients.