Purpose: This study was designed to investigate the characteristics of Korean adrenomyeloneuropathy (AMN) patients.Materials and Methods: We retrospectively selected 12 Korean AMN patients diagnosed by clinical analysis and increased plasma content of very long chain fatty acids.Results: All 12 patients were men.Patient ages at symptom onset ranged from 18 to 55 years.Family history was positive in two patients.The phenotype distributions consisted of AMN without cerebral involvement in seven patients, AMN with cerebral involvement in two patients, and the spinocerebellar phenotype in three patients.Nerve conduction studies revealed abnormalities in four patients and visual evoked tests revealed abnormalities in three patients.Somatosensory evoked potential tests revealed central conduction defects in all of the tested patients.Spinal MRI showed diffuse cord atrophy or subtle signal changes in all 12 patients.Brain MRI findings were abnormal in six of the nine tested patients.These brain abnormalities reflected the clinical phenotypes.Mutational analysis identified nine different ABCD1 mutations in 10 of 11 tested patients.Among them, nine have been previously reported and shown to be associated with various phenotypes; one was a novel mutation.Conclusion: In conclusion, the present study is the first to report on the clinical and mutational spectrum of Korean AMN patients, and confirms various clinical presentations and the usefulness of brain MRI scan.
Rimed vacuole을 가진 원위 근육병(distal myopathy with rimmed vacuoles, DMRV)은 제2형 유전성 봉입체 근육병으로도 불리며 초기 성인기에 발병하여 원위부의 근력약화를 보이는 임상양상과 rimmed vacuole의 근육병리소견을 특징으로 하는 상염색체 열성의 근육병이다. 이러한 DMRV의 원인은 UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) 유전자의 돌연변이임이 밝혀져 있다. 저자들은 원위부 근력약화를 호소하는 환자에서 전체 엑솜 염기서열분석을 이용하여 GNE 유전자의 복합 이형접합성 돌연변이(p.Asp176Val 및 p.Val572Leu)를 확인하여 DMRV를 진단할 수 있었다. 본 연구는 근육병의 정확한 분자진단에 있어서 전체 엑솜 염기서열분석의 유용성을 보여주었기에 이를 보고하는 바이다. Distal myopathy with rimmed vacuoles (DMRV) or hereditary inclusion body myopathy 2 is an autosomal recessive muscular disorder characterized by early adult-onset weakness of distal muscles and rimmed vacuoles in muscle biopsy. Mutations in the UDP-N-acetylglucosamine 2-epimerase/N-ace-tylmannosamine kinase (GNE) gene are associated with the development of DMRV. In this study, whole exome sequencing (WES) revealed compound heterozygous GNE mutations of p.Asp176Val and p.Val572Leu in a patient with distal limb weakness. Three hundred healthy controls did not show these mutations. All other variants found in distal myopathy-relevant genes were polymorphic. These findings confirmed that the patient had DMRV. This work underscores the usefulness of WES in improving the molecular diagnosis of myopathy.
We reported an age 32 male with progressive proximal muscle weakness. The serum creatine kinase was 1,908 IU/L. The muscle biopsy from biceps brachii muscle showed nonspecific myopathic changes. The whole exome sequencing identified a heterozygous variant (c.296A>C) in <i>CAV3</i>. It was previously reported as a likely pathogenic variant. It was also detected in the male’s mother and brother. However, his mother and brother had only hyperCKemia without muscle weakness. Our case showed phenotypic heterogeneity in a family, with the same variant in <i>CAV3</i>.
Purpose:The underlying cause of myasthenia gravis (MG) is unknown, although it likely involves a genetic component.However, no common genetic variants have been unequivocally linked to autoimmune MG.We sought to identify the genetic variants associated with an increased or decreased risk of developing MG in samples from a Korean Multicenter MG Cohort.Materials and Methods: To determine new genetic targets related to autoimmune MG, a whole genome-based single nucleotide polymorphisms (SNP) analysis was conducted using an Axiom TM Genome-Wide ASI 1 Array, comprising 598375 SNPs and samples from 109 MG patients and 150 neurologically normal controls.Results: In total, 641 SNPs from five case-control associations showed p-values of less than 10 -5 .From regional analysis, we selected seven candidate genes (RYR3, CACNA1S, SLAMF1, SOX5, FHOD3, GABRB1, and SACS) for further analysis.Conclusion: The present study suggests that a few genetic polymorphisms, such as in RYR3, CACNA1S, and SLAMF1, might be related to autoimmune MG.Our findings also encourage further studies, particularly confirmatory studies with larger samples, to validate and analyze the association between these SNPs and autoimmune MG.
We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG.A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups.After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen's kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation.While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice.
Abstract To understand the characteristics of Korean patients with anti-HMGCR myopathy, we measured anti-HMGCR antibodies and analyzed clinical, radiological, and pathological features. We measured titers of anti-HMGCR antibodies in the sera of 99 patients with inflammatory myopathy using the enzyme-linked immunosorbent assay. We tested 16 myositis-specific autoantibodies (MSAs) in all patients with anti-HMGCR myopathy. Positivity for the anti-HMGCR antibody was observed in 17 (4 males and 13 females) of 99 patients with inflammatory myopathy. The median age at symptom onset was 60 years. Ten (59%) of the anti-HMGCR positive patients had taken statins. The most common symptoms were proximal muscle weakness in 15 (88%), followed by myalgia in 9 (53%), neck weakness in 4 (24%), dysphagia in 3 (18%), and skin lesions in 2 (12%). The median titer of anti-HMGCR antibody was 202 U/ml. We found eight different MSAs in nine (53%) patients. The median disease duration from symptom onset to diagnosis was significantly shorter in the MSA-positive group than in the MSA-negative group (p = 0.027). In conclusion, our study is the first to measure anti-HMGCR antibodies with inflammatory myopathy, and identify new findings including the coexistence of other MSAs in Korean patients.
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