Schutz Peter W, Scalco Renata S, Barresi Rita, Houlden Henry, Parton Matthew, Holton Janice L
Division of Neuropathology, UCL Institute of Neurology, Queen Square, London, UK.
Muscle Immunoanalysis Unit, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; The John Walton Muscular Dystrophy Research Centre and MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Neuromuscul Disord. 2017 Aug;27(8):738-741. doi: 10.1016/j.nmd.2017.04.012. Epub 2017 Apr 27.
Mutations in calpain-3 cause limb girdle muscular dystrophy 2A. Biopsy pathology is typically dystrophic, sometimes characterized by frequent lobulated fibres. More recently calpain mutations have been shown in association with eosinophilic myositis, suggesting that calpain mutations may render muscle susceptible to inflammatory change. We present the case of a 33-year old female with mild proximal muscle weakness and high CK levels (6698 IU/L at presentation). Muscle biopsy showed clusters of fibre necrosis associated with very dense macrophage infiltrates and small numbers of lymphocytes, raising the possibility of an inflammatory myopathy. No eosinophils were observed. Immunosuppressive treatment was started without clinical improvement. MRI demonstrated bilateral fatty replacement in posterior thigh and calf muscles. Western blot results prompted Sanger sequencing of the calpain-3 gene revealing compound heterozygous mutations c.643_663del and c.1746-20C>G. Our case widens the myopathological spectrum of calpainopathies to include focal macrophage rich inflammatory change.
钙蛋白酶-3突变会导致2A型肢带型肌营养不良症。活检病理通常呈营养不良性，有时以频繁出现分叶状纤维为特征。最近发现钙蛋白酶突变与嗜酸性粒细胞性肌炎有关，这表明钙蛋白酶突变可能使肌肉易发生炎症变化。我们报告一例33岁女性病例，该患者有轻度近端肌无力，肌酸激酶水平较高（初诊时为6698 IU/L）。肌肉活检显示纤维坏死灶伴有非常密集的巨噬细胞浸润和少量淋巴细胞，提示存在炎性肌病的可能性。未观察到嗜酸性粒细胞。开始免疫抑制治疗后临床症状未改善。磁共振成像显示双侧大腿后部和小腿肌肉脂肪替代。蛋白质印迹结果促使对钙蛋白酶-3基因进行桑格测序，结果显示复合杂合突变c.643_663del和c.1746-20C>G。我们的病例拓宽了钙蛋白酶病的肌病理谱，使其包括以巨噬细胞为主的局灶性炎症变化。
