Mitochondrial Causes of Epilepsy: Evaluation, Diagnosis, and Treatment

Hannah E. Steele, MBBS, MRCP; Patrick F. Chinnery, PhD, FRCP, FRCPath


Semin Neurol. 2015;35(3):300-309. 

In This Article

Mitochondrial Disease Overview

Mitochondrial disorders are genetically determined metabolic diseases arising due to biochemical deficiency of the respiratory chain. They affect around 1 in 5,000 of the population in the United Kingdom (UK).[16]

The mitochondrial respiratory chain sits in the inner mitochondrial membrane and is responsible for the efficient generation of ATP through the process of oxidative phosphorylation (OXPHOS). The chain comprises five complexes, each with multiple subunits, which are coded for by both mitochondrial and nuclear genomes. A relevant mutation in either genome may therefore compromise respiratory chain function with resultant cellular ATP deficiency. Consequently, the clinical features of mitochondrial disorders are most evident in tissues with high-energy demands, with the central and peripheral nervous systems being particularly susceptible.

Recognition of mitochondrial phenotypes may be complex. However, there are certain features (Fig. 1) that suggest a bioenergetic deficit. Specific symptom combinations may enable a clinician to diagnose one of the canonical mitochondrial disorders such as MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), or MERRF (myoclonic epilepsy and ragged-red fibers). However, many individuals are oligo-symptomatic and consequently do not fulfil requirements for a syndromic diagnosis.

Figure 1.

An illustration of the common systemic features of mitochondrial disease. CNS, central nervous system; CPEO, chronic progressive ophthalmoplegia; ENT, ear, nose, and throat; PNS, peripheral nervous system.