dysferlinopathy患者40例临床和病理分析

An analysis of clinical features and pathology in 40 patients with dysferlinopathy

目的回顾性分析40例dysferlinopathy患者临床及活检骨骼肌组织化学、免疫组织化学染色病理变化，探讨dysferlinopathy的临床、病理诊断价值。方法对40例dysferlinopathy患者临床资料进行分析；并对活检骨骼肌进行组织化学、免疫组织化学染色病理分析。结果患者一般临床表现：进行性加重的肌无力、萎缩；根据病初受累肌群分为：肢带型肌营养不良2B型27例，Miyoshi远端型肌营养不良12例，以及胫骨前肌起病的远端肌病1例；血肌酸激酶水平呈不同程度的升高（134—19795U／L）；全部患者肌电图呈肌源性损害；12例行骨骼肌MRI，其中9例行双侧大、小腿MRI检查，3例行双侧小腿MRI检查；近端肌受累为主4例、腓肠肌受累为主7例、胫骨前肌受累为主1例。骨骼肌活检组织化学染色病理表现：肌纤维变性、坏死和再生活跃，结缔组织不同程度增生，16例可见肌内膜、肌束膜和小血管周围炎性细胞浸润；抗一dysferlin单克隆抗体免疫组织化学染色结果显示，30例dysferlinopathy患者肌纤维膜上dysferlin蛋白完全缺失，10例重度减低。结论本病典型临床表现为进行性加重肌无力、肌萎缩，根据病初受累肌群区分临床表型；血肌酸激酶显著增高，符合膜蛋白破坏型肌营养不良特点；骨骼肌MRI可清晰判断受累肌群范围、程度，帮助判断临床表型及选择合适的骨骼肌活检部位；病理特点为肌营养不良改变，部分患者有炎性细胞浸润，需要结合临床与炎性肌病相鉴别；肌纤维膜dysferlin蛋白缺失或重度减低，是dysfefiinopathy分子病理诊断的重要依据。

Objective To analyze retrospectively the clinical manifestations, features of the biopsy of skeletal muscle with histochemistry and immunohistochemistry staining of 40 patients with dysferlinopathy and investigate its clinical, pathological diagnostic value. Methods The clinical data, features of the biopsy of skeletal muscle with histochemistry, immunohistochemistry staining of 40 patients with dysferlinopathy were analyzed. Results Chronic progressive weakness and wasting were the general clinical manifestations. In our study, it was divided into three phenotypes according to the involved muscles of dysferlinopathy： 27 cases with proximal muscle, 12 cases with the gastrocenemius, 1 case with the tibialis anterior muscle. The serum creatine kinase levels all had a rise in different degree （ 134--19 795 U/L）. All the patients showed myogenic lesions in electrophysiologic study. 12 patients underwent skeletal muscle MRI. Proximal muscle was involved in 4 cases; gastrocnemius muscle was mainly involved in 7 cases; and anterior tibial muscle initially was involved in 1 case. All 40 cases showed active muscle fiber degeneration, necrosis and regeneration on muscle pathology. Connective tissues were proliferated and inflammatory cells infiltrated in endomysium, perimysium and perivascular sites of 16 patients. Immunohistochemical staining with anti-dysferlin monoclonal antibody identified the deficiency of dysferlin in the sareolemma of 30 cases with dysferlinopathy, and dysferlin was severely reduced in 10 cases. Conclusion Progressive weakness and wasting of skeletal muscle are the clinical manifestations of dysferlinopathy. The early involved muscles determine the clinical phenotype of dysferlinopathy. High serum creatine kinase levels show that dysferlinopathy is a membrane protein null disease. Muscle MRI of lower limbs may reflect the involvedmuscles, which is essential for clinical phenotypes and selecting muscle biopsy. The pathological characters of dysferlinopathy are changes of muscular dystrophy. Inflammatory cellular infiltration is relatively common in biopsied muscles of many dysferlinopathy patients, and dysferlinopathy needs to be differentiated from inflammatory myopathies. The deficiency or severely decreased dysferlin on the sarcolemma in immunohistochemical staining with anti-dysferlin monoclonal antibody is an important information for diagnosing dysferlinoapthy.