부산대학교 도서관

• Fatigue is a common symptom in α-dystroglycanopathy muscular dystrophies. • Fatigue did not predict abnormal NMJ transmission on electrodiagnostic studies. • NMJ defect was not found outside of the GMPPB α-dystroglycanopathy subgroup. • NMJ defect associates with mild GMPPB phenotypes and treatment response is variable. A postsynaptic dysfunction of the neuromuscular junction has been reported in patients with alpha-dystroglycanopathy associated with mutations in guanosine diphosphate (GDP)-mannose pyrophosphorylase B gene (GMPPB), some of whom benefit from symptomatic treatment. In this study, we determine the frequency of myasthenic and fatigue symptoms and neuromuscular junction transmission defects in a fukutin-related protein (FKRP)-predominant alpha-dystroglycanopathy cohort. Thirty-one patients with alpha-dystroglycanopathies due to mutations in FKRP (n = 25), GMPPB (n = 4), POMGNT1 (n = 1), and POMT2 (n = 1) completed a six-question modified questionnaire for myasthenic symptoms and the PROMIS Short Form v1.0-Fatigue 8a survey, and they underwent 3 Hz repetitive nerve stimulation of spinal accessory nerve-trapezius and radial nerve-anconeus pairs. Results showed that fatigue with activity was common; 63% of the cohort reported fatigue with chewing. A defective postsynaptic neuromuscular junction transmission was not identified in any of the patients carrying FKRP mutations but only in one mildly affected patient with GMPPB mutations (c.79 G>C, p.D27H and c.402+1G>A, splice site variant). We conclude that symptoms of fatigue with activity did not predict abnormal neuromuscular junction transmission on electrodiagnostic studies in this cohort and that, unlike GMPPB subgroup, a defective neuromuscular junction transmission does not appear to be present in patients with FKRP- associated muscular dystrophies. [ABSTRACT FROM AUTHOR]