Clinicopathologic Classification of Mitochondrial Disorders 

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Diversity: The presentations of mitochondrial disorders are very variable. This variability reflects the interplay between genetics, dosage effect, distribution of abnormal mitochondria, and the mitochondrial function being affected. This diversity is not limited to clinical presentation but also in the age of initial presentation. In some cases, a mitochondrial disease presents abruptly in a child or adult who up to that point had developed normally. Straight forward diagnosis of a mitochondrial disease is rare.

Common clinical presentations: Head

• MERRF syndrome type presentation: Combinations of ataxia, seizures, and myoclonus.

• MELAS syndrome type presentation: recurrent small strokes, migraine, and the unusual type of seizures.

• Ophthalmoplegic retinitis pigmentosa with polyneuropath, optic atrophy (Leber type), or deafness (Kearns-Sayre syndrome)

• Lactate level: Most but not all patients with mitochondrial abnormalities show elevated level of lactate or of lactate to pyruvate ratios in the blood and CSF. Such elevation is most provoked by exercise, however, even this is not always fool proof.

Classification:  Head  

It is inappropriate to classify mitochondrial diseases based simply on genetics, enzymology, or clinicopathologic features. The same genetic mutation can produce different clinical symptoms and signs. Critical parameters influencing the eventual clinicopathologic characteristics include the nature of mutation, particularly point mutation vs. deletion, and proportion of abnormal mitochondria in the cells. Albeit, the followings are the core syndromes that can be recognized and each may have their own variants:

• Alpers disease (etiology is disputable)

• Myopathy, encephalopathy, lactic-acidosis, and stroke like episodes (MELAS)

• Myoclonus epilepsy, ragged-red fibers (MERRF)

• Ragged red fibers polymyopathy (RRFP)

• Kearns-Sayre syndrome (KSS)

• Leigh's disease (subacute necrotizing encephalomyelopathy)

• Congenital lactic acidosis and recurrent ketoacidosis (CLARK)

• Leber's hereditary optic neuropathy (LHON)

• Neuropathy, ataxia, and retinitis pigmentosa (NARP)

• Chronic progressive external ophthalmoplegia (CPEO)

• Myoneurogastrointestinal encephalopathy (MNGIE)

• Luft syndrome

• mtDNA breakage syndrome

• mtDNA depletion syndrome

  For Comment: KarMing-Fung@ouhsc.edu