伴过度自噬X连锁肌病1例并文献复习

X-linked myopathy with excessive autophagy:a case report and literature review

目的报道1例伴过度自噬X连锁肌病(XMEA)病例并结合文献分析总结XMEA的临床表现、肌肉影像、肌肉病理及遗传学特点。方法收集2018年6月就诊于山东大学齐鲁医院并被确诊为XMEA的患者的病史、体格检查、实验室检查、肌肉影像、肌肉病理及遗传学资料进行总结,从Pubmed、知网及万方数据库检索相关文献并对该疾病的临床和遗传学特点进行分析。结果本例患者为40岁男性,因“发现肌酸激酶升高并双下肢无力4年”入院。患者自小学时出现下蹲时脚后跟不能着地,运动能力弱于同龄人。入院前多次检测肌酸激酶水平升高(320~1167 U/L);下肢肌肉磁共振成像显示双大腿股外侧肌、大收肌以及双小腿腓肠肌对称性脂肪变性;肌肉病理结果示肌纤维内自噬性空泡伴肌膜特征,且空泡膜上可见膜攻击物复合体沉积。基因检测证实患者VMA21基因存在c.*6A>G半合子突变。检索国内外相关文献,儿童及成人发病的XMEA患者多表现为肢体近端为主的肌无力和(或)肌萎缩,进展缓慢,多数患者预期寿命不受影响;而婴儿时期发病的XMEA患者容易合并多系统受累,疾病进展快,死亡风险高。结论XMEA是一种极为罕见的遗传性自噬性空泡肌病,尽管不同年龄段起病的XMEA患者其临床及预后表现有较大差异,但病理改变相对一致,基因检测是该疾病的主要确诊方法。

Objective To report a case of X-linked myopathy with excessive autophagy(XMEA)and review the literature aiming to analyze the clinical manifestations,muscle imaging,muscle pathology and genetic characteristics of the disease.Methods The medical history,physical and laboratory examination,muscle imaging and pathology,and genetics of a patient with XMEA who was admitted to QiLu Hospital of Shandong University in June 2018 were retrospectively collected.PubMed,CNKI,and Wanfang Data were searched for relevant literature.Results This patient was a 40-year-old male who complained of hyper creatine kinase and weakness in his lower extremities for 4 years.Since elementary school,his heels could not touch the ground when squatting and his motor performance was inferior to his peers.Abnormal creatine kinase levels(320-1167 U/L)were identified several times prior to admission.Magnetic resonance imaging of lower extremities revealed symmetrical fat replacement in bilateral lateral femoral muscles,adductor major and medial head of the gastrocnemius.Muscle biopsy showed intrafibrillar autophagic vacuoles with sarcolemmal features as well as membrane attack complex depositing on the vacuolar membrane;genetic analysis confirmed a hemizygous mutation c.*6A>G in VMA21 gene.Searching the literature,it was found that the onset age of XMEA patients varied from newborns to adulthood.Those XMEA patients with childhood or adulthood-onset mostly exhibited muscle weakness and(or)atrophy in the proximal limbs,with slow progression and normal life expectancy,while those with infant onset were prone to multiple system involvement,rapid disease progression,and high risk of death.Conclusions XMEA is an extremely rare hereditary autophagic vacuolar myopathy.Although the clinical and prognostic manifestations of XMEA patients vary greatly among different age groups,the muscle pathological changes are relatively consistent,and genetic testing is the main diagnostic method for this disease.