Neuromuscular Junction Abnormalities in Mitochondrial Disease: An Observational Cohort Study

Neurol Clin Pract. 2021 Apr;11(2):97-104. doi: 10.1212/CPJ.0000000000000795.

Abstract

Objective: To determine the prevalence of neuromuscular junction (NMJ) abnormalities in patients with mitochondrial disease.

Methods: Eighty patients with genetically proven mitochondrial disease were recruited from a national center for mitochondrial disease in the United Kingdom. Participants underwent detailed clinical and neurophysiologic testing including single-fiber electromyography.

Results: The overall prevalence of neuromuscular transmission defects was 25.6%. The highest prevalence was in patients with pathogenic dominant RRM2B variants (50%), but abnormalities were found in a wide range of mitochondrial genotypes. The presence of NMJ abnormalities was strongly associated with coexistent myopathy, but not with neuropathy. Furthermore, 15% of patients with NMJ abnormality had no evidence of either myopathy or neuropathy.

Conclusions: NMJ transmission defects are common in mitochondrial disease. In some patients, NMJ dysfunction occurs in the absence of obvious pre- or post-synaptic pathology, suggesting that the NMJ may be specifically affected.