以慢性进行性四肢近端无力为主要表现的McLeod综合征(附1例报告及文献复习)

Patient with McLeod Syndrome Presenting with Chronic Proximal Limb Weakness

目的报道1例以慢性进行性四肢近端无力为主要表现的McLeod综合征患者的临床表现及基因突变特点。方法收集先证者及家系成员的临床资料。采用重复引物多聚酶链反应和毛细管电泳以及全外显子测序进行基因检测,并用定量实时PCR验证检出的外显子缺失。结果先证者为1例67岁男性患者,主要临床表现为进行性近端为主的四肢肌无力,伴肌萎缩10年;无不自主运动等锥体外系损害表现及认知损害。血生化检查提示轻度贫血和高肌酸激酶血症;肌电图和神经传导速度检查提示慢性感觉运动神经元或轴索损害;肯尼迪病致病基因AR未发现突变。该先证者长期诊断未明,保持随访。先证者在病程15年时,其外孙因休克在医院就诊发现高肌酸激酶血症,基因检测发现XK基因3号外显子缺失。继之发现先证者也携带存在XK基因3号外显子缺失,进一步行外周血棘红细胞电镜检查提示红细胞中棘红细胞占比为24%,最终诊断为McLeod综合征。结论长期原因不明的四肢近端无力,电生理提示感觉及运动神经元或轴索损害的患者,虽无锥体外系损害表现,也需要考虑McLeod综合征可能,尤其是合并贫血和高肌酸激酶血症的患者。

Aim To investigate the clinical and genetic features of a patient with McLeod syndrome presenting with chronic proximal limb weakness.Methods The clinical data of the proband was collected.The genetic testing included the triplet repeat primed polymerase chain reaction(TP-PCR)and capillary electrophoresis for the dynamic mutation of AR,the whole exon sequencing.The exon deletion detected was further confirmed by quantitative real-time PCR.Results The proband was a 67-year-old male patient presenting with progressive limb weakness and muscle atrophy for 10 years.More proximal part was affected than the distal one.The biochemical testing indicated mild anemia and hyperckemia.The electromyography(EMG)and nerve conduction studies indicated widespread chronic neurogenic damage in the bulbar,cervical,thoracic,and lumbosacral segments and the sensory conduction and SNAP were also affected.The dynamic mutation of AR gene in Kennedy disease was not found.The diagnosis of the proband was uncertain and followed up in our clinic.Five years later,his 14-year-old grandson was found hyperckemia.The genetic testing of whole exon sequencing showed a hemizygous deletion of exon 3 in XK gene.The proband was confirmed the same mutation by quantitative real-time PCR.The acanthocyte of the proband accounted for 24%of the red blood cells detected by the electron microscope.He was finally diagnosed as McLeod syndrome.Conclusion McL eod syndrome should be considered in patients with sensorimotor neuropathy of undefined etiology,especially in those with hyperckemia or anemia,though no extrapyramidal lesions were observed.