Nonspecific mitochondrial disease with epilepsy in children: diagnostic approaches and epileptic phenotypes

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This study sought to characterize epileptic phenotypes in children with nonspecific mitochondrial disease (MD) and to evaluate MD diagnostic approaches. A retrospective analysis of the medical, electroencephalogram, and laboratory records of 142 patients with epilepsy was performed. The patients were evaluated for MD, and 124 patients were included in the final cohort. The MD criteria used included an oral glucose lactate stimulation test (OGLST) and urine organic acid/plasma amino acid (UOA/PAA) assays as metabolic indicators of modified Walker criteria, as suggested by Bernier et al. (Neurology 59:1406-1411, 2002). Twenty-two patients were classified as having definite MD (9), probable MD (5), possible MD (6), or pyruvate dehydrogenase (PDH) deficiency (3), including one patient which showed a respiratory chain (RC) defect and PDH deficiency. Seven out of eight patients in whom significant RC defects were observed showed complex I defects. In 14 patients, epileptic seizures start at infantile ages. Of 17 patients who substantially presented generalized seizures, 4 patients started with partial seizures. Five patients consistently presented only partial seizures. The OGLST and UOA/PAA assays were useful for a more precise diagnosis of MD, although low positive predictive value of the OGLST was regrettable. No patient was classified as definite MD by Walker's original criteria, but the use of our revised MD criteria resulted in the classification of nine additional patients as definite MD. MD manifested considerable diverse epileptic phenotypes and should be considered in the differential diagnosis of epilepsy in children with unexplained encephalomyopathy and progressive and fluctuating clinical courses.