Yanyan Ma1, Ting Xiong1, Guohua Lei2, Jiaqi Ding3, Rui Yang1, Zunbo Li4, Jun Guo5, Dingguo Shen6. 1. Department of Neurology, Xi'an Gaoxin Hospital, Xi'an Medical College, Xi'an, 710075, China. 2. Domestic Department of Health Management Institute, Chinese People's Liberation Army General Hospital, Beijing, 100853, China. 3. Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi'an, 710038, China. 4. Department of Neurology, Xi'an Gaoxin Hospital, Xi'an Medical College, Xi'an, 710075, China. lzb88031347@126.com. 5. Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi'an, 710038, China. guojun_81@163.com. 6. Department of Neurology, Chinese People's Liberation Army General Hospital, Beijing, 100853, China.
Abstract
BACKGROUND: Congenital myasthenic syndrome (CMS) is a heterogeneous group of rare disorders with impaired neuromuscular transmission caused by genetic defects, which is characterized by fatigable muscle weakness. CASE PRESENTATION: Herein, we report a case of limb-girdle CMS (LG-CMS) in a 15-year-old Chinese girl with limb weakness and mild ptosis. The patient presented with well-defined clinical manifestations, muscle imaging, and electrophysiological features associated with CMS. On muscle biopsy, in addition to tubular aggregates identified, an extremely unusual pathological change of rimmed vacuoles in muscle fibers was observed. Whole-exome sequencing disclosed two novel heterozygous variants (c.14 T>A and c.581 T>C) in the human glutamine-fructose-6-phosphate transaminase 1 (GFPT1) gene, leading to the substitutions of phenylalanine to tyrosine (p.F5Y) and serine (p.F194S), respectively. Both variants were predicted to be likely pathogenic by SIFT, Polyphen-2, and Mutation Taster. Treatments with pyridostigmine bromide and albuterol produced a dramatic improvement. CONCLUSIONS: Collectively, molecular genetic analysis and muscle biopsy play crucial roles in the diagnosis of GFPT1-related LG-CMS with rimmed vacuoles (a rare phenotype of CMS) and have important implications for treatment decision.
BACKGROUND:Congenital myasthenic syndrome (CMS) is a heterogeneous group of rare disorders with impaired neuromuscular transmission caused by genetic defects, which is characterized by fatigable muscle weakness. CASE PRESENTATION: Herein, we report a case of limb-girdle CMS (LG-CMS) in a 15-year-old Chinese girl with limb weakness and mild ptosis. The patient presented with well-defined clinical manifestations, muscle imaging, and electrophysiological features associated with CMS. On muscle biopsy, in addition to tubular aggregates identified, an extremely unusual pathological change of rimmed vacuoles in muscle fibers was observed. Whole-exome sequencing disclosed two novel heterozygous variants (c.14 T>A and c.581 T>C) in the humanglutamine-fructose-6-phosphate transaminase 1 (GFPT1) gene, leading to the substitutions of phenylalanine to tyrosine (p.F5Y) and serine (p.F194S), respectively. Both variants were predicted to be likely pathogenic by SIFT, Polyphen-2, and Mutation Taster. Treatments with pyridostigmine bromide and albuterol produced a dramatic improvement. CONCLUSIONS: Collectively, molecular genetic analysis and muscle biopsy play crucial roles in the diagnosis of GFPT1-related LG-CMS with rimmed vacuoles (a rare phenotype of CMS) and have important implications for treatment decision.
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