Anesthetic management in Charcot-Marie-Tooth disease type 2 due to a mutation in the mitofusin-2 gene

Abstract

Sir, Charcot-Marie-Tooth disease (CMT) is a neuromuscular disorder characterized by length-dependent degeneration of the motor and sensory nerve fibers, with a prevalence of 1 in 2,500 (about 200,000 patients in the European Union). Anesthesia is administered on this population more frequently than on normal people, as CMT patients often need orthopedic surgery to correct muscle imbalance and limb deformities, and for osteo-synthesis of bone fractures as they are prone to falls. Good anesthetic management in such patients includes prevention and prompt treatment of potential, although rare, complications such as malignant hyperthermia; awareness of prolonged responses to neuromuscular blocking drugs and toxicity caused by inappropriate doses in case of severe muscle wasting; and avoidance of a medication-induced exacerbation of neuropathy.[1–4] CMT is a genetically heterogeneous disorder, but so far, anesthesiology literature has never considered the patients′ gene mutations; and many studies not even the CMT type; though the occurrence of these complications might depends on the genetic defect. We recently administered anesthesia to a patient with a mutation (Arg280His) in the gene that encodes for mitofusin-2, a large and ubiquitously expressed mitochondrial transmembrane protein required for mitochondrial fusion.[5] The 73-year-old woman underwent anesthesia for two different surgical procedures (umbilical hernioplasty; transvaginal hysteroannexiectomy) at a 22-month interval. She elicited a history of severe lower-limbs sensory worsening with loss of independent ambulation after epidural anesthesia for hip osteo-synthesis, performed three years earlier. We chose a totally intravenous anesthesia for both procedures.[6] Propofol and fentanyl intravenous were used for induction and maintenance; lungs were ventilated using disposable circuits and a ventilator unpolluted by volatile anesthetics, with a mixture of air and oxygen. Atracurium was administered to facilitate intubation and for neuromuscular blockade, in the first intervention. Temperature was monitored using an esophageal thermal probe. Dantrolene was kept available. At the end of the surgical procedures, neuromuscular blockade was reversed with atropine and prostigmine. After the first intervention, on recovering ability to follow verbal commands, trachea was extubated. However, during the postoperative period, the saturation fell to 80% as a result of hypopnea/apnea, and the patient was mechanically ventilated for 2½ hours. After the second intervention too, the patient had severe hypoventilation and was mechanically ventilated for about 10 hours. This is the first report of anesthetic management of a patient with a mutation in the mitofusin-2 gene, the most common cause of axonal CMT (CMT type 2A-2). Further research is necessary to understand whether the mitofusin-2 pathology plays a role in delaying the adequate recovery of spontaneous breathing. We suggest that the possibility of developing this complication be considered when dealing with patients affected with this form of CMT.