1216 X-Linked Myotubular Myopathy in a Symptomatic Female Carrier

Abstract

X-Linked myotubular myopathy (XLMTM) is a rare genetic neuromuscular disorder characterized by mild to severe muscle weakness. It is caused by a mutation in the myotubularin (MTM1) gene. The diagnosis is considered in young male neonates with muscle weakness and hypotonia. The disorder predominantly affects males, but female carriers develop a range of symptoms. Only 24 cases of symptomatic female carriers are reported in the literature. We present a case of a woman with XLMTM who was evaluated for nocturnal hypoventilation. A 24-year-old woman diagnosed in 2012 with XLMTM reported morning headaches and frequent gasping with waking. She denied daytime sleepiness, snoring, insomnia, or symptoms of restless legs or narcolepsy. Spirometry showed a restrictive pattern with a proportionate reduction of FVC and FEV1 that significantly decreased in the supine position. Daytime arterial blood gas demonstrated a normal pH of 7.44, pO2 of 92 mmHg, and pCO2 of 38 mmHg. A polysomnogram in November 2013 demonstrated mild obstructive sleep apnea with an AHI of 7.7 with an oxygen saturation nadir of 73.7% and oxygen desaturation less than 90% of 20.3 minutes. A BiPAP titration with transcutaneous carbon dioxide (TCO2) monitoring demonstrated a baseline awake TCO2 of 55–60 mmHg and sleep TCO2 of 60–70 mmHg. Respiratory muscle weakness due to neuromuscular disease can cause insufficient ventilation and result in excessive daytime sleepiness and morning headaches. Pulmonary function testing shows a restrictive pattern with a FVC reduction of >10% in the supine position, reduced maximal inspiratory and expiratory pressures, and reduced total lung capacity. A polysomnogram with carbon dioxide monitoring can assess for hypoventilation. Management of respiratory muscle weakness due to neuromuscular disease can provide symptomatic relief, improve quality of life, and prolong life. Options for respiratory support include noninvasive positive pressure ventilation (NPPV) or invasive positive pressure ventilation.