分子病理确诊的肢带型肌营养不良2A型患者五例临床及病理特点

Clinical and pathological features of the 5 Limb-girdle muscular dystrophy 2A patients

目的 通过总结5例肢带型肌营养不良2A型（LGMD2A）患者的病例资料,探讨其临床和病理特点.方法 对病理诊断排除LGMD2B（7例）之后的30例分型未明的LGMD患者的肌肉标本进行免疫组织化学染色和钙激活蛋白酶-3（calpain-3）蛋白免疫印迹分析.结果 30例患者肌肉标本中有5例calpain-3蛋白条带缺失或遗留痕迹,从而被确诊为钙蛋白酶肌病,即LGMD2A.该5例患者起病年龄10～45岁,病程2～10年.其中2例的同胞兄妹有相似的临床表现,而父母无异常,提示本病的常染色体隐性遗传方式.5例均以下肢近端肌无力起病,肌萎缩明显;血清肌酸激酶639～8237 U/L,平均2502 U/L,肌电图均为肌源性损害.5例肌肉活体组织检查病理符合典型肌营养不良的病理特点,表现为肌纤维大小明显不等,可见坏死伴吞噬及再生,内核纤维增多,还原型辅酶Ⅰ四氮唑还原酶染色2例见分叶状纤维.5例LGMD2A患者dystrophin、caveolin-3和α-、β-、γ-、δ-sarcoglycan免疫组织化学染色均正常,2例dysferlin染色减低,余3例正常.结论 LGMD2A的临床表现和肌活体组织检查病理均缺乏特异性,免疫印迹分析有助于此病的诊断和鉴别诊断.

Objective To investigate the clinical and molecular pathological features of limb-girdle muscular dystrophy 2A （LGMD2A） of Chinese patients. Methods Thirty cases of LGMD with excluding LGMD2B were included in this study. The muscle specimens were performed by a standard series methods of histochemistry, enzymohistochemistry, immunohistochemistry and Western blot. The clinical and molecular pathological features of LGMD2A were retrospective analyzed. Results Five cases with no or only trace expression of calpain-3 protein were diagnosed as calpainopathy （LGMD2A） by Western blot analysis. The age of onset of these 5 patients ranged from 10 to 45 years and the duration of the disease were about 2-10 years. Proximal muscles weakness and atrophy of lower limbs were predominantly involved. In all patients,symptoms progressed slowly. The ambulation could be retained for many years but running and jumping were impaired early. The serum creatine kinase level was elevated moderately to markedly. Electromyography showed myopathic patterns in all cases. Two siblings had similar symptoms indicating autosomai recessive inherited pattern. Pathologically, there was marked variation in fibre size and most small fibres were round. Some necrotic and regenerating fibers were seen. Fibres with centrally placed nuclei can be found frequently. No infiltrations of inflammatory cells were seen. Lobulated fibers were observed in 2 patients by NADH-TR stain. The expression of dystrophin, caveolin-3, α-, β-, γ- and δ-sarcoglycan protein were normally staining of 5 LGMD2A patients＇ specimens by immunohistochemistry. Two patients had reduced staining of dysferlin by immunohistochemistry study. Conclusions Clinical and pathological characteristics of our 5 LGMD2A patients are consistent with typical muscular dystrophy features reported in other countries. Identification of calpian-3 deletion by Western blot is essential for the diagnosis of calpainopathy.