Illness Can Precipitate Weakness in Patients with Dystroglycanopathies (IN1-2.004)

OBJECTIVE: To determine if the frequency of acute weakness in the setting of illness is higher in individuals with dystroglycanopathies (DGs) compared with another muscular dystrophy, Duchenne-Becker muscular dystrophy (DBMD). BACKGROUND: The DGs are a heterogeneous group of muscular dystrophies caused by deficient glycosylation of α-dystroglycan. We observed during a natural history study of DGs that participants frequently reported acute, severe muscle weakness in the setting of an illness. DESIGN/METHODS: Surveys were mailed to all patients with DBMD or a DG followed by the neuromuscular clinic for either research or clinical care. Participants were asked if they had ever had an episode of sudden progression of weakness and if so, for details of events around the time of the episode. IRB approval was obtained for all recruitment and data collection. RESULTS: Illness-associated sudden worsening or onset of weakness was reported by approximately half of individuals with a DG interviewed as part of a natural history study. When surveyed, forty-seven percent (9/19) of individuals with a DG (mutations in FKRP, FKTN, POMT2) reported illness-associated weakness, compared to 12.1% (3/31) with DBMD (p=0.010). The illness-associated weakness led to the diagnosis of muscular dystrophy in 25% (2/8) of individuals with a DG. Time from onset of weakness after onset of illness and symptoms of illness were similar in the two groups. However duration of illness and time to recovery were longer in patients with a DG. CONCLUSIONS: Our data suggests that sudden weakness associated with an illness is reported commonly by individuals with a DG, but rarely by those with DBMD. The episodes in people with DG are more severe and protracted. Neurologists should include dystroglycanopathy in the differential diagnosis of acute illness-associated weakness. Supported by: Paul D. Wellstone Muscular Dystrophy Cooperative Research Center (MDCRC) grant from the National Institutes of Health (Bethesda, MD) (NIH U54 NS053672). Disclosure: Dr. McGaughey has nothing to disclose. Dr. Eskuri has nothing to disclose. Dr. Stephan has nothing to disclose. Dr. Mathews has personal compensation for activities with Seaside Therapeutics. Dr. Mathews has received research support from PTC Therapeutics and GlaxoSmithKline, Inc.