Table 2.
Typical mitochondrial syndromes. Many patients do not show these full-blown clinical pictures and are affected by a variety of complex or partial pictures (myopathies, neuropathies, cardiomyopathies, encephalomyopathies, multisystemic diseases, and so on). The relative frequencies are indicative (specifically designed epidemiological studies are not available). mtDNA, mitochondrial DNA.
| Syndrome | Relative Frequency | Typical Feature(s) | Associated Feature(s) |
Inheritance | Most Frequent Genetic Findings | Treatment of Choice |
|---|---|---|---|---|---|---|
| Alpers syndrome | Very rare | Childhood myocerebrohepatopathy | Autosomal recessive | POLG mutations with secondary mtDNA depletion | Symptomatic (avoid valproate) |
|
| Autosomal dominant optic atrophy (ADOA) | Rare | Optic neuropathy (blindness) | Autosomal dominant | OPA1 mutations | Symptomatic | |
| Coenzyme Q10 deficiency | Very rare | Ataxia or myopathy or multi-system disease | Autosomal recessive | Various nuclear genes | Coenzyme Q10 | |
| Kearns–Sayre Syndrome (KSS) | Frequent | Ocular myopathy (ptosis, ophthalmoparesis) | Ataxia, cardiac conduction defects | Sporadic | Single large-scale deletion of mtDNA | Symptomatic |
| Leber hereditary optic neuropathy (LHON) | Very frequent | Optic neuropathy (blindness) | Maternal (low penetrance, higher in male smokers) | Various mtDNA mutations | Idebenone | |
| Leigh syndrome | Frequent | Severe pediatric encephalopathy | Autosomal recessive, X-linked or maternal | Various nuclear or mtDNA mutations (e.g., m.8993T > G) | Symptomatic | |
| Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) | Frequent | Stroke-like episodes | Cardiac involvement, hearing loss, diabetes | Maternal | m.3243A > G | Symptomatic |
| Myoclonic encephalopathy with ragged-red fiber (MERRF) | Frequent | Myoclonus | Ataxia, myopathy | Maternal | m.8344A > G | Symptomatic (e.g., Levetiracetam) |
| Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) | Very rare | Gastrointestinal dysmotility | Leukodystrophy, ocular myopathy, peripheral neuropathy | Autosomal recessive | TYMP mutations | Liver transplantation |
| Neuropathy, Ataxia, Retinitis Pigmentosa (NARP) | Rare | Ataxia | Neuropathy, retinitis pigmentosa | Maternal | m.8993T > G | Symptomatic |
| Non syndromic hearing loss (NSHL) | Frequent | Hearing loss | Maternal | m.1555A > G | Symptomatic (avoid aminoglycosides) |
|
| Progressive external ophthalmoplegia (PEO) | Very frequent | Ocular myopathy | Myopathy | Autosomal dominant, recessive, maternal, or sporadic | Various nuclear genes with secondary mtDNA multiple deletions, various mtDNA point mutations, mtDNA single large-scale deletion | Symptomatic |