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.

中文翻译：

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α-dystroglycanopathy 队列（FKRP 主导）肌无力特征的临床和电生理评估

据报道，与二磷酸鸟苷 (GDP)-甘露糖焦磷酸化酶 B 基因 (GMPPB) 突变相关的 α-dystroglycanopathy 患者出现神经肌肉接头的突触后功能障碍，其中一些患者受益于对症治疗。在这项研究中，我们确定了 fukutin 相关蛋白 (FKRP) 主导的 α-dystroglycanopathy 队列中肌无力和疲劳症状以及神经肌肉接头传递缺陷的频率。31 名因 FKRP (n = 25)、GMPPB (n = 4)、POMGNT1 (n = 1) 和 POMT2 (n = 1) 突变而患有 α-dystroglycanopathies 的患者完成了一份关于肌无力症状的 6 个问题改良问卷和 PROMIS Short Form v1.0-Fatigue 8a 调查，他们对脊髓副神经-斜方肌和桡神经-肘节对进行了 3 Hz 重复神经刺激。结果表明，活动疲劳很常见；63% 的队列报告咀嚼疲劳。在任何携带 FKRP 突变的患者中均未发现突触后神经肌肉接头传递缺陷，但仅在一名具有 GMPPB 突变（c.79 G > C，p.D27H 和 c.402 + 1G > A，剪接位点变异）的轻度受影响患者中发现）。我们得出的结论是，在该队列的电诊断研究中，活动疲劳的症状并不能预测异常神经肌肉接头传递，并且与 GMPPB 亚组不同，FKRP 相关肌营养不良症患者似乎不存在神经肌肉接头传递缺陷。在任何携带 FKRP 突变的患者中均未发现突触后神经肌肉接头传递缺陷，但仅在一名具有 GMPPB 突变（c.79 G > C，p.D27H 和 c.402 + 1G > A，剪接位点变异）的轻度受影响患者中发现）。我们得出的结论是，在该队列的电诊断研究中，活动疲劳的症状并不能预测异常神经肌肉接头传递，并且与 GMPPB 亚组不同，FKRP 相关肌营养不良症患者似乎不存在神经肌肉接头传递缺陷。在任何携带 FKRP 突变的患者中均未发现突触后神经肌肉接头传递缺陷，但仅在一名具有 GMPPB 突变（c.79 G > C，p.D27H 和 c.402 + 1G > A，剪接位点变异）的轻度受影响患者中发现）。我们得出的结论是，在该队列的电诊断研究中，活动疲劳的症状并不能预测异常神经肌肉接头传递，并且与 GMPPB 亚组不同，FKRP 相关肌营养不良症患者似乎不存在神经肌肉接头传递缺陷。