Mitochondrial Myopathies (MM)

Types of Mitochondrial Myopathies

Clinical classifications

Primary mitochondrial diseases are diverse and may present differently in different individuals. They can be generally organized into four main clinical groups, based on which organs are affected and what symptoms occur. These include:

Isolated Myopathic Forms - Primarily affect skeletal muscle. Common features include exercise intolerance, proximal muscle weakness, and in some cases, breathing problems (respiratory insufficiency). Examples include:

• Isolated mitochondrial myopathy caused by mtDNA or nDNA variants
• TK2-related myopathy
• Myopathic form of coenzyme Q10 deficiency

Ocular / Ophthalmoplegic Forms - Primarily affect the eye muscles, leading to drooping eyelids (ptosis) and eye movement weakness (ophthalmoplegia). Some patients may experience mild systemic involvement, but the eye symptoms are usually most prominent. Examples include:

• Chronic progressive external ophthalmoplegia (CPEO)
• Kearns–Sayre syndrome (KSS)

Encephalomyopathic Forms - Affect both skeletal muscle and the central nervous system (CNS). Infants and children may present with low muscle tone (hypotonia), developmental delay, seizures, or buildup of lactic acid in the blood (lactic acidosis). Examples include:

• Leigh syndrome
• Alpers–Huttenlocher syndrome (POLG-related mitochondrial disease)

Multisystem Forms - The most complex mitochondrial diseases, affecting muscle along with multiple organs, including the brain, heart, liver, kidneys, endocrine system, and gastrointestinal tract. Examples include:

• Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS)
• Myoclonic Epilepsy with Ragged-Red Fibers (MERRF)
• Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP)
• Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE)
• Maternally Inherited Diabetes and Deafness (MIDD)
• Pearson Bone Marrow–Pancreas Syndrome (Pearson syndrome)
• Barth Syndrome (Barth syndrome)
• Primary Coenzyme Q10 Deficiency, multisystem forms (multisystem forms of CoQ10 deficiency)

Mechanistic classifications

Alternatively, mitochondrial myopathies may also be categorized by the types of genetic or biochemical defects that cause them, rather than solely by clinical features (as above). These categories reflect the nature of the underlying mutations. For example:

Single large-scale mtDNA deletion syndromes – Caused by sporadic, single large deletions of mitochondrial DNA (typically not inherited). Examples include:

• CPEO
• KSS
• Pearson syndrome

mtDNA point mutations – Single changes in mtDNA affecting specific mitochondrial proteins. Examples include:

• MELAS
• MERRF
• NARP

Nuclear gene disorders of mtDNA maintenance (including depletion and multiple deletions) - Caused by mutations in nuclear genes required for mitochondrial DNA replication, repair, and nucleotide supply, leading to mtDNA depletion and/or multiple deletions. Examples (by gene) include:

• TK2
• RRM2B
• TWNK
• DGUOK
• POLG

Coenzyme Q10 biosynthesis defects – Mutations in nuclear genes that reduce production of coenzyme Q10, a key mitochondrial molecule. Examples include:

• Primary CoQ10 deficiency

Additional reading

• Ahuja AS. Understanding mitochondrial myopathies: a review. PeerJ. 2018 May 21;6:e4790. doi: 10.7717/peerj.4790. PMID: 29844960; PMCID: PMC5967365.
• Wen H, Deng H, Li B, Chen J, Zhu J, Zhang X, Yoshida S, Zhou Y. Mitochondrial diseases: from molecular mechanisms to therapeutic advances. Signal Transduct Target Ther. 2025 Jan 10;10(1):9. doi: 10.1038/s41392-024-02044-3. PMID: 39788934; PMCID: PMC11724432.

Last reviewed May 2026.