Mitochondrial myopathies
Mitochondrial myopathies are inherited disorders of oxidative phosphorylation, most caused by maternally transmitted mitochondrial DNA mutations, that preferentially disable skeletal muscle, brain, retina, and heart. Named syndromes include MELAS, MERRF, Kearns-Sayre syndrome, chronic progressive external ophthalmoplegia, and Leigh syndrome. Diagnosis proceeds from lactate and muscle biopsy to genetic testing; management is supportive, built around seizure control and toxin avoidance.
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What this article covers
- Overview
Definition: the mitochondrial myopathies are genetic disorders of oxidative phosphorylation, the respiratory chain process that generates cellular energy; skeletal muscle and the central nervous…
- Epidemiology
Onset spans childhood to early adulthood: the mitochondrial myopathies follow a fluctuating course with a wide spectrum of systemic comorbidity, from an isolated myopathy to combined neurologic…
- Risk factors
Maternal family history: a relative in the maternal line with unexplained fluctuating weakness, ophthalmoplegia, hearing or vision loss, or stroke-like episodes raises suspicion, since mitochondrial…
- Pathophysiology
Two genomes, two inheritance rules: mitochondrial DNA is transmitted only through the egg, so a pathogenic mtDNA mutation follows a maternal pattern, while nuclear genes encoding many respiratory…
- Clinical features
Shared pattern across the syndromes: fluctuating, often proximal, exercise-intolerant weakness varying in severity between relatives with the same mutation, commonly with ophthalmoplegia, bulbar…
- Differential diagnosis
Idiopathic inflammatory myopathy (dermatomyositis or polymyositis): proximal weakness too, but onset is acute to subacute, the course is not fluctuating, and creatine kinase is highly elevated (dermatomyositis).
- Diagnosis
Diagnosis rests on a compatible clinical pattern confirmed by elevated lactate, muscle biopsy showing ragged red fibers, and genetic testing of mitochondrial or nuclear DNA; first exclude the mimics…
- Management
No disease-modifying or curative treatment exists for the underlying oxidative phosphorylation defect, so management centers on symptom control, avoidance of added mitochondrial or muscle stress, and organ surveillance.
- Complications
Stroke-like episodes and their sequelae: in MELAS, episodes that do not respect a vascular territory can leave residual cognitive impairment, focal deficits, or recurrent encephalopathy.
- Prognosis
Course tracks heteroplasmy and organ involvement, not one fixed trajectory: the mutant mtDNA load differs between tissues and between people, so the same mutation can range from an isolated, slowly…
- Prevention
Genetic counseling for maternal-line relatives: a mother carrying a pathogenic mtDNA mutation transmits it to all of her children regardless of sex, so genetic counseling before pregnancy is appropriate for a known carrier.
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