Brody myopathy associated with novel compound heterozygous ATP2A1 mutations (P6-8.015)

Abstract

<h3>Objective:</h3> To describe a case of presumed Brody myopathy associated with novel compound heterozygous ATP2A1 mutations. <h3>Background:</h3> Brody myopathy is a rare autosomal recessive skeletal muscle disease characterized by exertional muscle cramps, weakness, and/or rhabdomyolysis associated with clinical myotonia. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 19-year-old man with normal development and motor milestones presented to neuromuscular clinic after two episodes of exercise-induced muscle weakness and rhabdomyolysis in the past 6-months. Peak creatinine phosphokinase (CPK) was &gt;63,000 units/L and he quickly returned to baseline after each episode with intravenous fluids and supportive care. Remaining initial testing including serum total carnitine and acylcarnitine levels, and urine organic acid levels, were normal. He provided additional history of progressive difficulty relaxing leg and handgrip muscles after exertion since childhood, and multiple episodes of asymptomatic dark-colored urine provoked by strenuous exercise over the past two years. Physical examination showed bilateral grip and percussion myotonia with otherwise normal muscle bulk, strength, and remaining neurologic examination. Electromyography was normal. Genetic testing including myotonic dystrophy types 1 and 2, Pompe disease, and non-dystrophic myotonic disorders was notable for compound heterozygous ATP2A1 gene c.2032C&gt;T (p.Arg678Cys) and c.2176G&gt;A (p.Val726Met) variants of uncertain significance. Separate pathogenic mutations in this gene cause Brody myopathy, a non-dystrophic myotonic disorder characterized by exertional rhabdomyolysis. The patient is presumed to have Brody myopathy due to novel compound heterozygous ATP2A1 mutations. <h3>Conclusions:</h3> Brody myopathy should be considered in individuals presenting with muscle cramps, clinical myotonia, and exertional rhabdomyolysis. Clinical features and electromyographic findings are milder than myotonic dystrophies, Pompe disease, and typical non-dystrophic myotonic disorders. Genetic testing including ATP2A1 gene sequencing aids diagnosis. Management is supportive, although individuals should be aware of a 5% association with malignant hyperthermia-like episodes after exposure to volatile anesthetics. <b>Disclosure:</b> Dr. Walia has nothing to disclose. Dr. Su has nothing to disclose.