Actazolamide to treat congenital myopathy caused by SCN4A mutation

Abstract

Listen

Translate article

Objective: SCN4A encodes the alpha subunit of the skeletal muscle voltage-gated sodium channel, vital for the generation and propagation of the muscle action potential and muscle contraction. Sodium channel dysfunction typically results in myotonia and periodic paralysis. Acetazolamide is a common treatment for these disorders. Recently, SCN4A mutations have also been associated with congenital myopathy. We sought to ascertain if acetazolamide could be beneficial in an individual with SCN4A congenital myopathy. Methods: Clinical assessment pre and post acetazolamide therapy. Genetic analysis was performed at the Neurogenetics Unit, National Hospital for Neurology and Neurosurgery as provided by the Channelopathy Highly Specialised National Service for rare disease. Results: We present a 16 year old girl diagnosed with congenital myopathy due to compound heterozygous SCN4A mutations (c.311G > Ap.Arg104His, c.3403C > Tp.Arg1135cys). She has been on non-invasive ventilation at night since age 6 and had a scoliosis repair age 12. From age 8 she has been taking slow release salbutamol which resulted in overall improvement in limb function but from age 11 she began to complain of daily episodic leg weakness usually after school. Acetozolamide was started in July 2015 at a dose of 62.5 mg bd and has gradually been increased to 250 mg in the morning and 125 mg at night. Since starting the Acetozolamide there has been an improvement in overall levels of fatigue and a cessation of the daily attacks of leg weakness. The only side effects she experienced were tingling of the mouth, hands and feet on initiation of treatment which subsequently resolved. Conclusion: From this case Acetozolamide appears to be a promising agent in maintaining muscular function in those with SCN4A related congenital myopathy. This may be mutation specific as her point mutation (c.311G > Ap.Arg104His, c.3403C > Tp.Arg1135cys) alters channel function in a manner comparable to other periodic paralysis mutations.