Table II.

Mitochondrial myopathy typically presenting without PEO.

Syndrome	Clinical symptoms/signs	Onset age	Genetics
Childhood or adult onset
Myopathy, encephalopathy, lactic acidosis, stroke like episodes (MELAS)	Stroke-like episodes with encephalopathy, migraine, seizures. Variable presence of myopathy, cardiomyopathy, deafness, endocrinopathy, ataxia. A minority of patients have PEO	Typically < 40 years of age but childhood more common	mtDNA point mutations (m.3243A>Gin 80%)
Myoclonus, epilepsy, and ragged red fibres (MERRF)	Stimulus-sensitive myoclonus, generalized seizures, ataxia, cardiomyopathy. A minority of patients have PEO	Childhood	mtDNA point mutations (m.8344A>Gmost common)
Ataxia neuropathy syndromes (ANS): Including MIRAS, SCAE, SANDO, MEMSA	Sensory axonal neuropathy with variable degrees of sensory and cerebellar ataxia. PEO in 50%. Epilepsy and dysarthria are present in some	Adult onset	nDNA mutations (POLG, TWINKLE, OPA1)
Mitochondrial myopathy (isolated) Congenital or infant-onset	Axial/proximal myopathy. May have other features of mitochondrial disease (ataxia, polyneuropathy)	Any age of onset	mtDNA point mutations (multiple, including A3243G); mtDNA single large-scale deletions
Congenital or infant-onset
Mitochondrial DNA depletion syndrome	Diffuse myopathy or hepatocerebral syndrome	Congenital or infantile presentation, with hypotonia, respiratory weakness, and death within few years of life. Infantile COX-deficiency myopathy occasionally reverses after first year of life	nDNA mutations (DGK, TK2, TWINKLE, POLG)
Infantile myopathy with COX-deficiency	Diffuse myopathy, lactic acidosis, encephalopathy	Congenital/infantile onset. Fatal in first year, or reversible after first year in some patients	mtDNA mutation (m.l4674T>C) in the reversible form

MEMSA = myoclonic epilepsy myopathy sensory ataxia; MIRAS = mitochondrial recessive ataxia syndrome; SANDO = sensory ataxia neuropathy dysarthria ophthalmoplegia; SCAE = spinocerebellar ataxia with epilepsy.