What are mitochondrial myopathies (Mitochondrial Myopathies)?

From the Guidelines

Mitochondrial myopathies are a diverse group of genetic disorders that affect the mitochondria, leading to multisystem dysfunction, particularly in energy-demanding tissues like muscles and the nervous system. These disorders result from mutations in either mitochondrial DNA or nuclear DNA that affect mitochondrial proteins, disrupting cellular energy production 1. The clinical presentation of mitochondrial myopathies can vary widely, but they often involve a combination of neuromuscular and non-neuromuscular symptoms, including muscle weakness, cardiomyopathy, and neurological abnormalities 1.

Key Characteristics of Mitochondrial Myopathies

• Affect any part of the body, with organs with high energy requirements being particularly vulnerable 1
• Can present with a variety of clinical syndromes, including Barth Syndrome, a rare X-linked recessive mitochondrial myopathy 1
• Often involve a combination of neuromuscular and non-neuromuscular symptoms, including muscle weakness, cardiomyopathy, and neurological abnormalities 1
• Can be caused by mutations in either mitochondrial DNA or nuclear DNA that affect mitochondrial proteins 1

Management and Treatment

• Treatment focuses on symptom management and supportive care, as there is no definitive cure 1
• A multidisciplinary approach is recommended, including neurologists, cardiologists, and other specialists based on affected systems
• Coenzyme Q10, L-carnitine, and riboflavin are commonly prescribed supplements that may help improve mitochondrial function and energy production
• Physical therapy and occupational therapy are essential to maintain muscle strength and prevent contractures, and to help patients adapt to limitations in daily activities
• Regular cardiac and respiratory monitoring is necessary, as these systems are often affected 1
• A balanced diet rich in antioxidants is beneficial, though specialized "mitochondrial diets" have limited evidence
• Patients should avoid medications known to impair mitochondrial function, including certain antibiotics like aminoglycosides, valproic acid, and statins in some cases
• Genetic counseling is important for family planning 1

From the Research

Definition and Overview of Mitochondrial Myopathies

• Mitochondrial myopathies (MM) are a group of rare disorders characterized by impaired oxidative phosphorylation, leading to energy production defects in cells and organs 2.
• These disorders can cause severe disease and death, with genetic mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) being the primary cause 2.
• MM can present with a multitude of symptoms, affecting virtually all organ systems, with prominent muscular symptoms such as muscle weakness being common 2.

Clinical Presentation and Diagnosis

• The clinical presentation of MM may include isolated myopathy with muscle weakness, exercise intolerance, chronic ophthalmoplegia/ophthalmoparesis (cPEO), and eyelids ptosis, or multisystem conditions with extramuscular signs and symptoms 3.
• Diagnostic approaches utilize genetic sequencing, including next-generation sequencing techniques, to aid in molecular diagnosis and heteroplasmy detection in MM patients 4.
• Adjunctive tests such as functional and exercise testing can aid in surveillance of MM patients 4.

Management and Treatment

• Management of MM requires a multi-disciplinary approach, including systemic screening for comorbidities, cofactor supplementation, avoidance of substances that inhibit the respiratory chain, and exercise training 4.
• Treatment is generally supportive and emphasizes symptom management, with no cure available for these diseases as of today 2.
• Some therapies, such as speech therapy, physical therapy, and respiratory therapy, have been used in MM with variable results, but are not curative and aim to maintain a patient's current abilities to move and function 2.

Awareness and Research

• There is a lack of awareness and expertise in the medical community regarding MM, presenting huge obstacles to diagnosis and provision of coordinated multidisciplinary care for these patients 5.
• Research funding levels for MM tend to be low compared to more common diseases, but identifying genetic defects responsible for MM has led to investigations into potential treatments 2.
• Recent advances in next-generation sequencing techniques have substantially improved diagnosis, and new therapeutic targets have been identified, leading to promising clinical trials 3.