Elevated urinary β2 microglobulin in the first identified Japanese family afflicted by X-linked myopathy with excessive autophagy

Here we report what is to our knowledge the first identified Japanese family afflicted by X-linked myopathy with excessive autophagy. The index case is a 52-year-old man with almost 40 years of progressive proximal muscle weakness. High urinary β2 microglobulin, normal serum β2 microglobulin, autophagic vacuoles with sarcolemmal features, and a hemizygous c.164–7T>G mutation in the VMA21 gene were found. His two maternal uncles had similar clinicopathological findings. High urinary β2 microglobulin without obvious renal dysfunction might result from decreased urine acidification in the distal convoluted tubules caused by the VMA21 gene mutation. These findings might prove to be useful as a preliminary marker suggestive of X-linked myopathy with excessive autophagy.     

M蛋白相关性杆状体肌病3例及文献回顾

目的 对3例怀疑M蛋白相关性杆状体肌病患者进行肌肉病理检查、M蛋白筛查明确诊断,提高对这一罕见疾病的认识并探讨对此疾病的诊疗方案。 方法 报道3例M蛋白相关性杆状体肌病,结合文献复习对病例特点进行总结。 结果 3例患者均表现为进行性加重的肌肉无力症状,完善肌肉活检诊断为杆状体肌病,合并M蛋白,给予行自体造血干细胞移植治疗有效。 结论 散发的晚发型成人杆状体肌病是一种罕见的、亚急性进展的肌病,常合并M蛋白,针对清除M蛋白的治疗是有效的。     

临床药师参与1例普伐他汀致肌炎的药学实践

目的:通过本例案例报道,提示临床规范和合理用药。方法:通过药学查房,对患者用药史的详细询问及后期循证取证,判断药物相关性不良反应的可能性及停用可疑药物,以减轻患者的不良反应症状及分析不良事件的原因。结果:停用可疑药物6d后患者全身肌痛减轻,实验室检查值逐步恢复正常。结论:对于初次使用他汀类药物的患者,初始剂量应从小剂量开始,且密切关注息者的肝功能和血肌酸激酶水平。     

Deep sequencing detects very-low-grade somatic mosaicism in the unaffected mother of siblings with nemaline myopathy

When an expected mutation in a particular disease-causing gene is not identified in a suspected carrier, it is usually assumed to be due to germline mosaicism. We report here very-low-grade somatic mosaicism in ACTA1 in an unaffected mother of two siblings affected with a neonatal form of nemaline myopathy. The mosaicism was detected by deep resequencing using a next-generation sequencer. We identified a novel heterozygous mutation in ACTA1, c.448A>G (p.Thr150Ala), in the affected siblings. Three-dimensional structural modeling suggested that this mutation may affect polymerization and/or actin’s interactions with other proteins. In this family, we expected autosomal dominant inheritance with either parent demonstrating germline or somatic mosaicism. Sanger sequencing identified no mutation. However, further deep resequencing of this mutation on a next-generation sequencer identified very-low-grade somatic mosaicism in the mother: 0.4%, 1.1%, and 8.3% in the saliva, blood leukocytes, and nails, respectively. Our study demonstrates the possibility of very-low-grade somatic mosaicism in suspected carriers, rather than germline mosaicism.     

Localized scleroderma and regional inflammatory myopathy

Inflammatory myopathy is rare in localized scleroderma. We report 2 new cases of regional inflammatory myopathy associated with localized scleroderma and review 10 reported cases of localized scleroderma associated with an inflammatory myopathy with regional muscle involvement, more often in the upper extremities. Serum creatine kinase was mildly elevated or normal. Histopathology often showed perimysial inflammation and plasma cell infiltration. These cases demonstrate that inflammatory myopathy should be considered in patients with localized scleroderma and regional muscle weakness, pain or atrophy. Muscle biopsy can confirm the diagnosis of myositis, which if identified, will require anti-inflammatory and/or immunosuppressive therapy.     

Frequency and phenotype of patients carrying TPM2 and TPM3 gene mutations in a cohort of 94 patients with congenital myopathy

Congenital myopathies are difficult to classify correctly through molecular testing due to the size and heterogeneity of the genes involved. Therefore, the prevalence of the various genetic causes of congenital myopathies is largely unknown. In our cohort of 94 patients with congenital myopathy, two related female patients and two sporadic, male patients were found to carry mutations in the tropomyosin 2 (TPM2) and tropomyosin 3 (TPM3) genes, respectively. This indicates a low (4.3%) frequency of TPM2 and TPM3 mutations as a cause of congenital myopathy. Compared to previously described patients carrying the same mutations as found in our study (c.503G > A, and c.502C > T in TPM3, and c.415_417delGAG in TPM2), clinical presentation and muscle morphological findings differed in our patients. Differences included variation in distribution of muscle weakness, presence of scoliosis and ptosis, physical performance and joint contractures. The variation in clinical profiles emphasizes the phenotypic heterogeneity. However, common features were also present, such as onset of symptoms in infancy or childhood, musculoskeletal deformities and normal or low plasma levels of creatine kinase.One patient had nemaline myopathy and fiber size disproportion, while three patients had congenital fiber type disproportion (CFTD) on muscle biopsies. TPM2-related CFTD has only been described in two cases, indicating that mutations in TPM2 are rare causes of CFTD.     

Myo-Spain: Registro de pacientes con miopatía inflamatoria idiopática de España. Metodología

ObjectivesTo describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM.MethodsObservational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM.ConclusionsMyo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis.     

抗HMGCR/SRP抗体阳性的特发性炎性肌病特点分析

目的:探讨抗HMGCR/SRP抗体阳性的特发性炎性肌病(IIM)的临床和病理特点。方法:收集HMGCR/SRP抗体阳性的IIM患者5例,对其危险因素、临床表现、实验室检查、肌电图、肌肉MRI、肌肉病理、肌炎自身抗体及药物治疗进行分析。结果:抗HMGCR/SRP抗体阳性的IIM患者临床变异较大,但大多有肌肉无力;血清肌酸激酶均较高;5例患者肌电图均表现为典型的肌源性损害。肌肉MRI主要表现为肌肉水肿。3例为典型坏死性肌病表现,1例镜下偶见肌细胞坏死,1例为多发性肌炎表现。HMGCR抗体阳性患者其中1例为正服用他汀药物,另一患者服用抗精神病药物;SRP抗体阳性患者1例为自身免疫性疾病患者,1例长期服用他汀,另1例病因未明确。激素治疗效果不一,2例加用丙种球蛋白治疗,1例加用免疫抑制剂治疗。结论:抗HMGCR/SRP抗体阳性的IIM临床表现各异,肌电图仅能定位肌肉损害,主要依靠肌肉活检,肌炎自身抗体检查更有助于诊断和具体分型,疗效各型不一。     

Clinical and Pathological Features of Korean Patients with DNM2-Related Centronuclear Myopathy

Background and Purpose

Centronuclear myopathy (CNM) is characterized by the presence of central nuclei within a large number of muscle fibers. Mutations of the dynamin 2 gene (DNM2) are common causes of autosomal dominant or sporadic CNM. The aim of this study was to characterize the clinical and pathological features of CNM relative to the presence of DNM2 mutations.

Methods

Six patients with clinical and pathological features of CNM were recruited. Detailed clinical and pathological findings were analyzed according to the presence of DNM2 mutations.

Results

We detected DNM2 mutations in four of the six sporadic CNM patients, and identified the following distinct clinical and pathological features in those patients with DNM2 mutations: preferential involvement of the distal lower limbs, typical nuclear centralization, and radially distributed sarcoplasmic strands in muscle pathology. In contrast, those without DNM2 mutations exhibited rather diffuse muscular involvement, and nuclear internalization and myofibrillar disorganization were more pronounced features of their muscle pathology.

Conclusions

These findings suggest the presence of specific features in Korean CNM patients. A detailed clinical and pathological examination of CNM patients would be helpful for molecular genetic analyses of this condition.