Table 3.

The systemic manifestations and genetic correlation of main PMDs. POLG (DNA polymerase subunit gamma), OPA (optic atrophy), TYMP (thymidine phosphorylase), RRM2B (Ribonucleotide-diphosphate reductase subunit M2 B).

Mitochondrial Syndromes	Symptoms	Most Frequent Mutations Reported
Mitochondrial Encephalopathy, Lactacidosis, and Stroke-like episodes (MELAS) [26]	Encephalopathy, myopathy, headache, and focal neurological deficits. Other features are cardiac conduction disorders, diabetes, and chronic fatigue.	mtDNA m.3243A>G (80% of cases) m.3271T>C m.3252A>G m.13513G>A
Maternally Inherited Diabetes and Deafness (MIDD) [27]	Family histories of diabetes and SNHL. Other features are encephalatrophy, cerebellar ataxia, migraine, and stroke.	mtDNA m.3243A>G (>80% of cases)
Kearns-Sayre syndrome (KSS) [28] Progressive External Ophthalmoplegia (PEO)	KSS manifests with progressive external ophthalmoplegia (PEO). The main feature is ptosis but can also present as an overlapping syndrome.	nDNA POLG1 or OPA1 mtDNA m.3243A>G 4977bp deletion
Myoclonic Epilepsy with Ragged red Fibers (MERF) [29]	Progressive myoclonic epilepsy is often associated with ataxia.	mtDNA m. 8344A>G
Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) [30]	Progressive gastrointestinal dysmotility, cachexia, PEO, neuropathy, and leukoencephalopathy.	nDNA TYMP, POLG, or RRM2B