Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
BMC Neurol. 2022 May 3;22(1):168. doi: 10.1186/s12883-022-02690-6.
HINT1 mutations cause an autosomal recessive axonal neuropathy with neuromyotonia. This is a first case report of coexistence of myasthenia gravis (MG) and HINT1-related motor axonal neuropathy without neuromyotonia.
A 32-year-old woman presented with recurrent ptosis for 8 years, diplopia for 2 years and limb weakness for 1 year and a half. Neostigmine test, elevated AChR antibody level and positive repetitive nerve stimulation supported the diagnosis of MG. Electroneurography (ENG) and electromyography (EMG) examinations revealed a motor axonal neuropathy without neuromyotonic or myokymic discharges. Next-generation sequencing and Sanger sequencing were performed to identify the gene responsible for suspected hereditary neuropathy. Genetic testing for a HINT1 mutation was performed and revealed a homozygous mutation at c.278G>T (p. G93V). The patient was treated with pyridostigmine, oral prednisolone and azathioprine. Her ptosis and diplopia have significantly improved at 6-month follow-up.
Concurrence of MG and hereditary motor axonal neuropathy without neuromyotonia is quite rare. Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing the combination of MG and peripheral neuropathy. Early diagnosis is important for initial treatment and prognosis. The novel homozygous variant c.278G>T(p.G93V) contributes to the pathogenic variants spectrum of the HINT1 gene.
HINT1 突变导致常染色体隐性轴索性神经病伴肌强直。这是首例同时存在重症肌无力（MG）和 HINT1 相关运动轴索性神经病而无肌强直的病例报告。
一名 32 岁女性，8 年来反复出现眼睑下垂，2 年来出现复视，1 年半来出现肢体无力。新斯的明试验、乙酰胆碱受体抗体水平升高和重复神经刺激阳性支持 MG 的诊断。神经电图（ENG）和肌电图（EMG）检查显示运动轴索性神经病，无肌强直或肌纤维性颤动放电。进行下一代测序和 Sanger 测序以确定疑似遗传性神经病的相关基因。对 HINT1 突变进行基因检测，发现 c.278G>T（p.G93V）纯合突变。患者接受吡啶斯的明、口服泼尼松龙和硫唑嘌呤治疗。6 个月随访时，她的眼睑下垂和复视明显改善。
MG 和无肌强直遗传性运动轴索性神经病同时发生较为罕见。识别 MG 和周围神经病的组合时，应注意有无眼睑下垂和眼肌麻痹、肢体无力的分布和反射。早期诊断对初始治疗和预后非常重要。新型纯合变体 c.278G>T（p.G93V）有助于 HINT1 基因的致病变异谱。
