Multiple system atrophy (MSA) is a progressive disorder, characterized by cerebellar ataxia, parkinsonism, and autonomic dysfunction. Brains of patients with MSA show extensive glial cytoplasmic inclusions that contain α-synuclein in the oligodendrocytes as well as extensive neurodegeneration in the cerebellum and basal ganglia. The pathophysiologic mechanism of MSA is poorly understood; therefore, it has been difficult to develop effective therapy for this disorder.
Although MSA is predominantly sporadic, rare familial cases have been identified in Japan. Using whole-genome sequencing technology, COQ2 mutations have been identified as a genetic cause for MSA in these families.1 Heterozygous mutations of COQ2, in particularly the V393A mutation, are genetic risk factors for sporadic MSA in Japan but not in Europe or North America. Follow-up studies confirmed the association of COQ2 with MSA in a Taiwanese cohort and a Chinese cohort,2,3 but the association was not replicated in other studies from East Asia.4-6 Other European and North American studies also did not find the association between COQ2 mutations and MSA.7,8 These data suggest that the association between COQ2 mutation and MSA might be population-specific. A meta-analysis of East Asian cohorts (Japan, Taiwan, Korea, and China) supports the association of COQ2 mutations and MSA.3 Indeed, patients with MSA in different geographic regions have diverse clinical presentations: Japanese patients have primarily the cerebellar subtype, whereas European patients have mostly the parkinsonism subtype. Consistent with this finding, COQ2 mutations seem to be more common in patients with the cerebellar subtype of MSA.2
Kuo S, Quinzii CM. Coenzyme Q10 as a Peripheral Biomarker for Multiple System Atrophy. JAMA Neurol. 2016;73(8):917–919. doi:10.1001/jamaneurol.2016.1810
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