经基因检测确诊的3例成人家族型神经元核内包涵体病患者临床分析

Clinical analysis of 3 adult-onset patients with genetically diagnosed familial neuronal intranuclear inclusion disease

目的分析成年起病的家族型神经元核内包涵体病(NIID)患者的临床特点。方法广州医科大学附属第六医院神经内科在2021年8月、2022年1月、2022年8月经基因检测确诊3例成人家族型NIID患者,回顾性分析患者的临床表现、影像特点、病理特征、NOTCH2NLC基因突变特点、治疗方法及预后。结果3例患者的年龄分别为73、67、65岁,发病年龄分别为68、64、56岁。临床表现呈高度异质性。患者1中枢神经、周围神经及自主神经均受累,出现痴呆、癫痫、帕金森综合征、肌无力、尿毒症等症状;患者2仅累及中枢神经,出现帕金森综合征症状;患者3累及周围神经及自主神经,以反复呕吐为突出表现。3例患者头颅弥散加权成像(DWI)显示皮髓交界处持续非对称高信号。皮肤活检显示2例患者的部分汗腺导管上皮细胞、血管内皮细胞核内检出多个嗜酸性包涵体。基因检测显示3例患者NOTCH2NLC基因均存在GGC重复扩增突变,突变次数>134次。3例患者均以对症治疗为主,病情仍在逐渐进展。结论家族型NIID患者临床表现呈高度异质性,头颅DWI及皮肤活检有助于诊断,NOTCH2NL基因检测可确诊NIID。

Objective To analyze the clinical characteristics of adult-onset patients with familial neuronal intranuclear inclusion disease(NIID).Methods The clinical data of 3 patients with familial NIID genetically diagnosed in Department of Neurology,Sixth Affiliated Hospital of Guangzhou Medical University in August 2021,January 2022,and August 2022 were collected.Their clinical manifestations,imaging features,pathological features,Notch2 N-terminal-like C(NOTCH2NLC)gene mutation characteristics,treatment methods and prognoses were summarized retrospectively.Results The age of these 3 patients was 73,67,and 65 years,and the onset age was 68,64,and 56 years,respectively.The clinical manifestations are highly heterogeneous.In patient 1,the nervous centralis,peripheral nerves and autonomic nerves were involved,appearing dementia,epilepsy,Parkinson's syndrome,muscle weakness and uremia;in patient 2,only the nervous centralis were involved,presenting symptoms of Parkinson's syndrome;in patient 3,peripheral nerves and autonomic nerves were involved,prominently presenting with repeated vomiting.Skull diffusion weighted imaging(DWI)showed asymmetric high signal at the dermo-medullary junction in 3 patients.Acidophilic inclusion bodies in some sudoriferous duct epithelial cells,and vascular endothelial nucleus were found in the skin biopsy of 2 patients.All 3 patients completed NOTCH2NL gene test,and all had GGC repeat amplification mutations with mutation frequency>134.These 3 patients were mainly treated symptomatically,and the disease was still progressed gradually.Conclusion The clinical manifestations of familial NIID are highly heterogeneous;skull MRI characteristic changes and skin biopsy can help to diagnose NIID and NOTCH2NL gene detection can diagnose NIID.