Episodic weakness and Charcot-marie-tooth disease due to a mitochondrial MT-ATP6 mutation

Muscle Nerve. 2017 Jun;55(6):922-927. doi: 10.1002/mus.25453. Epub 2017 Feb 12.


Introduction: Episodic muscle weakness is the hallmark of a heterogeneous group of disorders known as periodic paralysis. A majority are due to single nucleotide mutations causing membrane depolarization.

Methods: We report 2 family members with chronic, slowly progressive, distal axonal neuropathy, or Charcot-Marie-Tooth disease type 2 (CMT2) and episodic weakness resembling periodic paralysis.

Results: Next generation sequencing (NGS) identified a mitochondrial MT-ATP6 mutation m.9185T>C (p.Leu220Pro) in both patients, consistent with a previous report of an association with this phenotype. The episodic weakness has been responsive to acetazolamide therapy for a few decades. By contrast, the underlying axonal neuropathy is quite progressive despite treatment with acetazolamide.

Conclusions: Mitochondrial DNA mutations should be considered in patients with a history of episodic weakness and axonal inherited neuropathy (CMT2). The episodic weakness is responsive to acetazolamide therapy, and electrophysiological testing for periodic paralysis with a long exercise protocol is negative in these cases. Muscle Nerve 55: 922-927, 2017.

Keywords: Charcot-Marie-Tooth disease; episodic weakness; inherited neuropathy; mitochondrial ATPase; periodic paralysis.

Publication types

  • Case Reports

MeSH terms

  • Charcot-Marie-Tooth Disease / genetics*
  • Family Health
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Mitochondrial Proton-Translocating ATPases / adverse effects
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Mutation / genetics*
  • Phenotype


  • MT-ATP6 protein, human
  • Mitochondrial Proton-Translocating ATPases