Katherine R Schon, Dominic G O'Donovan, Mayen Briggs, James B Rowe, Lokesh Wijesekera, Patrick F Chinnery, Jelle van den Ameele
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Despite raised CK, electromyography did not show myopathic changes. Exome gene panel testing was negative, but targeted genetic analysis revealed a hemizygous pathogenic variant in the XK gene c.895C > T p.(Gln299Ter), consistent with a diagnosis of McLeod syndrome. The patient died of sepsis, and autopsy showed astrocytic gliosis and atrophy of the basal ganglia, diffuse iron deposition in the putamen, and mild Alzheimer's pathology. Muscle pathology was indicative of mild chronic neurogenic atrophy without overt myopathic features. He had non-specific cardiomyopathy and splenomegaly. McLeod syndrome is an ultra-rare neurodegenerative disorder caused by X-linked recessive mutations in the XK gene. Diagnosis has management implications since patients are at risk of severe transfusion reactions and cardiac complications. 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引用次数: 0
摘要
我们对一名经基因证实的麦克劳德神经棘细胞增多症综合征患者的临床、神经病理学和多系统特征进行了全面描述,包括视频和尸检结果。一名 61 岁的男子出现运动障碍和行为改变。检查显示他四肢有肌张力障碍性舞蹈样运动,深腱反射减弱,步态宽大。他患有口颌运动障碍,导致严重的吞咽困难。他在 30 多岁时首次发现血清肌酸激酶(CK)升高,但当时包括肌肉活检在内的检查均未得出结论。脑磁共振成像显示白质体积减少、基底节萎缩和慢性小血管缺血。尽管肌酸激酶(CK)升高,但肌电图并未显示肌病变。外显子组基因检测结果为阴性,但靶向遗传分析显示,XK基因c.895C > T p.(Gln299Ter) 存在半杂合子致病变异,与麦克劳德综合征的诊断一致。患者死于败血症,尸检显示其基底节有星形胶质细胞增生和萎缩,普坦门有弥漫性铁沉积,并有轻度阿尔茨海默病病理变化。肌肉病理显示为轻度慢性神经源性萎缩,但没有明显的肌病特征。他患有非特异性心肌病和脾肿大。麦克劳德综合征是一种超罕见的神经退行性疾病,由XK基因的X连锁隐性突变引起。由于患者面临严重输血反应和心脏并发症的风险,因此诊断对治疗具有重要意义。当怀疑有临床诊断时,应检查候选基因,而不是仅仅依靠外显子组。
We present a comprehensive characterization of clinical, neuropathological, and multisystem features of a man with genetically confirmed McLeod neuroacanthocytosis syndrome, including video and autopsy findings. A 61-year-old man presented with a movement disorder and behavioral change. Examination showed dystonic choreiform movements in all four limbs, reduced deep-tendon reflexes, and wide-based gait. He had oromandibular dyskinesia causing severe dysphagia. Elevated serum creatinine kinase (CK) was first noted in his thirties, but investigations, including muscle biopsy at that time, were inconclusive. Brain magnetic resonance imaging showed white matter volume loss, atrophic basal ganglia, and chronic small vessel ischemia. Despite raised CK, electromyography did not show myopathic changes. Exome gene panel testing was negative, but targeted genetic analysis revealed a hemizygous pathogenic variant in the XK gene c.895C > T p.(Gln299Ter), consistent with a diagnosis of McLeod syndrome. The patient died of sepsis, and autopsy showed astrocytic gliosis and atrophy of the basal ganglia, diffuse iron deposition in the putamen, and mild Alzheimer's pathology. Muscle pathology was indicative of mild chronic neurogenic atrophy without overt myopathic features. He had non-specific cardiomyopathy and splenomegaly. McLeod syndrome is an ultra-rare neurodegenerative disorder caused by X-linked recessive mutations in the XK gene. Diagnosis has management implications since patients are at risk of severe transfusion reactions and cardiac complications. When a clinical diagnosis is suspected, candidate genes should be interrogated rather than solely relying on exome panels.
期刊介绍:
Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.