Mitochondrial respiratory chain defects: underlying etiology in various epileptic conditions.

PURPOSE: To determine if defects in mitochondrial respiratory chain enzyme complexes (MRCs) contribute to the etiology of childhood epilepsy.

METHODS

We reviewed the clinical and laboratory features of 48 epileptic patients (23 male, 25 female) with MRC defects that were confirmed by biochemical assays using muscle biopsies.

RESULTS

(1) Thirty-five cases (72.9%) were MRC I deficient, one case (2.1%) was MRC II deficient, 11 cases (22.9%) were MRC IV deficient, and one case (2.1%) had combined MRC I and IV deficiencies. (2) In our clinical diagnosis, there were 10 cases (20.8%) with Leigh disease and one case each with myopathy, encephalopathy, lactic acidosis, stroke-like episodes (MELAS) or Alpers' disease (2.1%). Most of the remaining cases (75.0%) had uncategorized mitochondrial cytopathy with nonspecific encephalopathy. (3) For epileptic classification, there were two cases (4.2%) of Ohtahara syndrome, 10 cases (20.8%) of West syndrome, 12 cases (25.0%) of Lennox-Gastaut syndrome, two cases (4.2%) of Landau-Kleffner syndrome, 14 cases (29.2%) of generalized epilepsy, and eight cases (16.7%) of partial epilepsy. (4) The mean age of seizure onset was 2.68 +/- 2.21 (range: 1 month - 5.5 years). (5) Magnetic resonance imaging (MRI) showed diffuse cortical atrophy in 34 cases (70.8%), basal ganglia signal changes in 18 cases (37.5%) and thalamus signal changes in 12 cases (25.0%). (6) A ketogenic diet produced clinical improvements, including seizure reduction and global functional improvement in 75% of 24 patients.

CONCLUSIONS

MRC defects are one of the important causes of probably symptomatic childhood epilepsy. A ketogenic diet should be carefully considered for treatment of intractable epilepsy related to MRC defects.