Mitochondrial respiratory chain defects: underlying etiology in various epileptic conditions.
OBJECTIVE
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.
Lee
Young Mock
YM
Department of Pediatrics, Severance Children's Hospital, The Institute for Handicapped Children, Yonsei University College of Medicine, Seoul, Korea.
Kang
Hoon Chul
HC
Lee
Joon Soo
JS
Kim
Se Hoon
SH
Kim
Eung Yeop
EY
Lee
Seung Koo
SK
Slama
Abdelhamid
A
Kim
Heung Dong
HD
D000140:Acidosis, Lactic / Q000175:diagnosis; D000367:Age Factors; D017668:Age of Onset; D000927:Anticonvulsants / Q000627:therapeutic use; D001284:Atrophy; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D004569:Electroencephalography / Q000706:statistics & numerical data; D004827:Epilepsy / Q000175:diagnosis / Q000178:diet therapy / Q000209:etiology*; D005260:Female; D006801:Humans; D007662:Ketosis / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D028361:Mitochondrial Diseases / Q000150:complications* / Q000175:diagnosis / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology
D000927:Anticonvulsants