Table 1.

Typical mitochondrial myopathies that are generally multisystem disorders.

Myophathy	Pathogenesis	Inheritance	Age	Mitochondrial Target	Main Symptoms	Prognosis
Kearns-Sayre syndrome (KSS)	single large-scale deletions of mtDNA	generally, not inherited. (sporadic), rare case of mitochondrial, autosomal dominant, or autosomal recessive	before the age of 20	Mainly cyt C oxidase	progressive external ophthalmoplegia, and pigmentary retinopathy. cardiac conduction block, cerebrospinal fluid protein greater than 100 mg/dL, cerebellar ataxia, short stature, deafness, dementia, and endocrine abnormalities	slowly progressive disorder. Prognosis related to level of organs involvment. arrythmias
Chronic progressive external ophthalmoplegia (CPEO)	Deletion/mutation of mtDNA (i.e., tRNA at nucleotide 3243 in which there is an A to G), or nuclear genes: POLG, C10orf2, RRM2B, SLC25A4, POLG2, DGUOK, SPG7	sporadic, mitochondrial, autosomal dominant, or autosomal recessive	Aroud 40s years	defective function of oxidative phosphorylation	Ptosis, Limited eye movements, and Hearing loss, Mild muscle weakness, dysphagia, cataracts	prognosis depends on the associated features,
Leigh syndrome	Different pathogenic mutations identified in over 85 genes	nuclear or mtDNA mutations.	Generally, infancy and childhhod	Dysfunction of pyruvate dehydrogenase complex and oxidative phosphorylation	Mainly developmental delay or psychomotor regression failure to thrive, weakness/hypertonia, ataxia, oculomotor palsy, seizures, lactic acidosis	generally poor
Mitochondrial DNA depletion syndrome (MDS)	Different mutations in the TK2,SUCLA2, SUCLG1, RRM2B, DGUOK, MPV17, POLG, C10orf2; TYMP genes	Maternal and autosomal recessive	newborns, infants, children, or adult	different subunits of mitochondrial respiratory chain complexes	Different clinical pictures: Myopathic; encephalomyopathic; hepatocerebral; neurogastrointestinal	generally poor
Mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS)	mtDNA: m.3243A > G, gene MT-TL (80% of cases) and m.3271T > C tRNA mutation (10%)	maternally inherited	childhood	tRNA and NADH dehydrogenase	stroke-like episode, hemiparesis, hemianopia, or cortical blindness. focal or generalized seizures, recurrent migraine, vomiting, short stature, hearing loss, and muscle weakness.	poor
Myoclonus epilepsy with ragged red fibers (MERRF)	A-to-G transition at nucleotide 8344 (m.8344A > G) of the MT-TK genetRNA (Lys)	Spontaneous mutations, maternally inherited	Childhood, adolescence or early adulthood	oxidative phosphorylation	myoclonus, epilepsy, ataxia, myopathy, dementia, optic atrophy, deafness, peripheral neuropathy, spasticity, cardiomyopathy with WPW syndrome.	Generally poor. It can depend on age, severity of symptoms, organs involved.
Maternally inherited deafness and diabetes (MIDD)	mutation in mtDNA gene MT-TL1, encoding tRNA for leucine, and in rare cases in MT-TE and MT-TK genes, encoding tRNAs for glutamic acid, and lysine, respectively.	maternally inherited	mean age of onset is 30–40 years	defective function of oxidative phosphorylation	Diabetes, deafness, Chorioretinal abnormality, Dyschezia, Macular dystrophy, Malabsorption, Cerebellar hypoplasia, arrhythmias, heart failure, ophthalmoplegia, Muscular weakness,	prognosis for MIDD is better than that for MELAS
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)	Mutations of TYMP gene (nDNA)	autosomal recessive	range from 5–60 years of age	defective function of oxidative phosphorylation	gastrointestinal disorders (dysphagia, cramping, vomiting, diarrhea, gastroparesis intestinal pseudo-obstruction) related to abnormal bowel motility. Neurological symptoms includes chronic progressive ophthalmoplegia, sensorimotor peripheral neuropathy	progressive degenerative disorder with a poor prognosis
Neuropathy, ataxia, and retinitis pigmentosa (NARP)	More frequent: m.8993T > C/G subunit 6 of mt ATPase gene	maternally inherited	Childhood	defective function of oxidative phosphorylation	sensory neuropathy, muscle weakness; ataxia, retinitis pigmentosa, developmental delay, seizures, dementia, deafness, arrhythmias.	poor prognosis