Alteration in the copy number of mitochondrial DNA in leukocytes of patients with mitochondrial encephalomyopathies

OBJECTIVES: We investigated whether mutation of mitochondrial DNA (mtDNA) affects the copy number of the mitochondrial genome in patients with mitochondrial myopathy encephalopathy with lactic acidosis and stroke-like episodes (MELAS) and those with myoclonic epilepsy with ragged-red fiber (MERRF) syndromes. MATERIALS AND METHODS: Forty-eight Taiwanese patients with MELAS syndrome and 20 patients with MERRF syndrome were recruited in this study. RESULTS: In relation to controls, the copy numbers of mtDNA in leukocytes of patients with MELAS or MERRF syndrome were significantly higher at a young age but lower at an advanced age. In addition, MELAS patients harboring higher proportions of mtDNA with A3243G transition had lower mtDNA copy numbers. The MELAS or MERRF patients with multi-system disorders had lower mtDNA copy numbers in leukocytes. Furthermore, higher proportions of mtDNA with 4977 bp deletion were found in leukocytes of MERRF patients with multi-system involvement. CONCLUSION: In leukocytes, alteration in the copy number of mtDNA is related to the proportion of mtDNA with a point mutation or large-scale deletion, which may serve as a biomarker in the pathogenesis and disease progression of MELAS and MERRF syndromes.