肉芽肿性肌炎(GrM)是一组发生在横纹肌的非特异性上皮样肉芽肿性炎性反应综合征,临床上多表现为肌痛、肌无力、皮下结节和吞咽困难,可有肌酶不同水平的升高、炎性肌病的神经电生理表现.病理检查是确诊的主要手段,典型的肌肉病理可发现多核巨细胞和肌纤维炎性改变.肉芽肿性肌炎最常与结节病和结缔组织疾病伴发[1],少有同时合并重症肌无力的病例报道.我们在临床中发现了1例罕见的重症肌无力合并肉芽肿性肌炎的患者,从诊断和治疗过程中吸取了一定的经验教训,现对该病例和文献报道的7例类似病例进行分析,初步概括其特点,为临床同道提供借鉴.

目的 探讨杆状体肌病的临床特点、肌肉MRI改变和基因突变.方法 回顾性分析1例NEB基因新复合杂合突变致儿童型杆状体肌病患者的临床资料.结果 本例患者为男性,6岁发病,以双下肢远端无力起病,逐渐向近端发展,14岁行肌肉活检在肌纤维内发现大量杆状体而被确诊,29岁复诊时做基因检测明确为NEB基因突变.双下肢肌肉MRI提示双侧股外侧肌、股中间肌、大收肌萎缩并脂肪变性.双侧比目鱼肌脂肪变性并萎缩,腓肠肌内侧头和胫前肌水肿.与文献报道不同的是本例患者双下肢远端无力明显重于近端,且发病23年仍未累及颈肌和上肢肌肉.基因检测发现NEB基因有两处杂合突变,c.2549delA发生移码变异,c.21522+3A>G发生点突变,家系验证结果显示这两处杂合突变分别来自其父亲和母亲.目前文献报道NEB基因已发现有312种突变,本例发生在第27号外显子上的c.2549delA突变,在人类基因数据库和HGMDpro数据库中亦均未见有报道,为新发现的突变位点.结论 杆状体肌病临床表型异质性较大,肌肉病理和基因检测是诊断的重要依据,c.2549delA为NEB基因新发的突变位点.

Objective : To investigate the clinical features, skeletal muscle imaging, muscle pathology, blood smear and so on of neutral lipid storage disease with myopathy (NLSDM) caused by PNPLA2 gene mutation. Methods : The clinical data, skeletal muscle imaging, pathological data, and genetic test results of a patient with NLSDM treated in our hospital were collected in detail, and the previous literature was reviewed and compared. Results : The main symptoms were muscle weakness and muscular atrophy. Pathological findings of muscle biopsy showed fat deposition in muscle fibers with border cavitation. Fatty droplets were seen in the cytoplasm of neutrophils in peripheral blood. Magnetic resonance imaging of the muscles of both lower extremities showed that muscle in the thigh vastus intermedius , lateral muscles, biceps, and the muscle abdominal area of the middle leg were filled or replaced by fat. Genetic test results suggested mutations in the PNPLA2 gene. Conclusion : NLSDM is a rare clinical myopathy with abnormal lipid metabolism. Characteristic changes can be seen in skeletal muscle imaging and pathology. The detection of PNPLA2 gene mutation is an important basis for diagnosing NLSDM. Asymmetry and progressive limb weakness are the clinical features. Muscle MRI is mainly involved in the posterior group of the lower limbs. Jordans bodies in the peripheral blood smear and a large number of coarse-grained lipid deposits with rimmed vacuoles in muscle fibers are the characteristic pathological changes.

Objective: To investigate the clinical features, skeletal muscle imaging, and muscle pathological characteristics of late-onset GSD IIIa caused by mutation of the AGL gene in adults. Methods: The clinical data, skeletal muscle imaging, pathological data, and gene test results of a family with late-onset GSD IIIa in adulthood were collected in detail in November 2019. Results: The proband is a 40-years-old male, who was admitted into our hospital due to a 2-years history of limb weakness. The proband was diagnosed with the following syndrome: he had a 15-years history of elevated muscle enzymes; the cranial nerve examinations showed no abnormal findings; the muscle tension in both upper and lower limbs was low, and tendon reflexes were absent; the proband's muscle strength was 5 in the proximal muscles and 4 in the distal muscles of the upper limbs, with 3 in the proximal muscles and 4 in the distal muscles of the lower limbs; Magnetic Resonance Imaging (MRI) revealed abnormally high signal intensity changes in the posterior thigh muscle group, and the posterior-medial calf muscle group; and vacuoles were evident in some muscle fibers biopsied from the gastrocnemius muscle. Periodic acid-Schiff staining stained the cytoplasm of muscle fibers a dark red color. The proband's older brother exhibited the same clinical features. DNA analysis identified mutations in the AGL gene in the proband, his older brother, and parents. The proband and his older brother both carried two compound heterozygous mutations, c.866G>A and c.2855_2856insT. Pedigree analysis demonstrated that c.866G>A and c.2855_2856insT mutations had been inherited from the mother and father, respectively. Conclusion: Late-onset GSD IIIa in adults is clinically characterized by muscle weakness, muscle atrophy, and mainly occurred in the posterior thigh muscle group. We also identified two novel compound heterozygous mutations (c.866G> A and c.2855_2856insT) in the AGL gene.

目的 探讨伴有肌纤维坏死的脂质沉积性肌病患者的骨骼肌病理改变及其临床特点.方法 回顾性分析8例伴有肌纤维坏死的脂质沉积性肌病患者的肌肉组织病理改变和临床特点.结果 8例患者中上肢近端肌力3级以下者4例(其中2例伴呼吸肌受累),下肢近端肌力3级以下者6例;8例均伴有颈伸肌无力;8例患者除肌纤维内大量脂质沉积外,均伴有不同程度肌纤维变性坏死,其中5例偶见变性坏死肌纤维,坏死肌纤维比率0.1％～0.9％,病程较长且年龄偏大,有反复出现肌无力的病史;3例可见较多变性坏死纤维,坏死肌纤维比率＞1.0％,病程较短、进展迅速且较年轻,其中2例免疫组织化学结果显示CD4(一)、CD8(一)、CD20(--)、CD68(+);3例基因检测显示ETFDH基因突变.结论 部分脂质沉积性肌病患者的肌肉病理中可见变性坏死肌纤维,伴有明显肌纤维坏死者临床症状较重,病情进展较快.

Objective: To investigate the clinical features, skeletal muscle imaging, and muscle pathological characteristics of normokalemic periodic paralysis (NormoKPP) caused by mutation of SCN4A gene p.R675Q. Methods: The clinical data, skeletal muscle imaging, pathological data, and gene test results of a family with NormoKPP were collected in detail in October 2018. The previous literature was reviewed and used for comparative analysis. Results: The proband was a 28-year-old male with paroxysmal weakness of both lower limbs for 14 years. Limb weakness was mainly manifested in the proximal extremities of both lower limbs, which occurred two to three times a year. The muscle weakness of each attack lasted for 1-2 weeks and gradually recovered. The blood potassium levels were normal. The abnormal signals of the posterior thigh muscle group and the medial calf muscle group could be seen on the magnetic resonance imaging (MRI) of the skeletal muscle, and the target-fiber could be seen in some muscle fibers in muscle pathology. The father of the proband and his brother had the same symptoms. In the same family, 10 people received genetic testing. The results showed that five had a mutation of SCN4A gene p.R675Q. The mutation gene came from the father of the proband. Conclusion: NormoKPP is a clinically rare form of sodium ion channel disease. The clinical manifestations, skeletal muscle imaging, and pathological changes are different from the common hypokalemic periodic paralysis. SCN4A gene detection is an important means for the diagnosis of NormoKPP.