A Case of Inclusion Body Myositis with Clinical, Pathological and Serological Consideration

Inclusion body myositis is a rare condition of idiopathic inflammatory myopathy. Prior criteria for the diagnosis of inclusion body myositis essentially required pathological features of rimmed vacuoles, tubulofilamentous inclusions, and amyloid deposits. However, recently developed new diagnostic criteria emphasize clinical characteristics including weakness of finger flexors and knee extensors. In addition, a serological evaluation of anti-cN1A antibody is helpful for the diagnosis. We report a case of inclusion body myositis with clinical, pathological, and serological consideration.

Muscle and Nerve Biopsy in Various Neuromuscular Disorders / 대한신경근육질환학회지

Muscle and nerve biopsy may be vital diagnostic tools in various neuromuscular disorders. Since these procedures are invasive, it matters to decide when to perform a biopsy, which muscle or nerve to be selected, and how to interpret the pathologies. This review addresses the indications, methods of biopsies, and also significant pathological findings frequently encountered in muscle and nerve pathology.

Predominant Myofibrillar Pathology with Preserved Sarcolemmal Aquaporin 4 Immunoreactivity in a Patient with Neuromyelitis Optica-Associated HyperCKemia / 고신대학교의과대학학술지

A 49-year-old man developed recurrent myalgia and hyperCKemia during acute attacks of neuromyelitis optica. Muscle biopsy was performed, and the pathological findings were analyzed. Predominant myofibrillar pathology was observed, which constitutes a unique finding that has not been reported before. This case result shows that neuromyelitis optica-associated hyperCKemia can produce variable pathologic phenotypes. Further studies are needed to elucidate the relationship between myofibril destruction and aquaporin 4 autoimmunity.

Diagnostic Approaches to Various Muscle Diseases Based on Muscle Pathology

Muscle pathology can give much information to reach the diagnosis of neuromuscular disorders. Major pathological changes occurred in skeletal muscles include muscle fiber atrophy/hypertrophy, necrosis/regeneration, inflammation, myofibrillar disorganization, abnormal inclusions, and disruptions in cellular organelles. Physicians should be able to understand what each of these findings indicates. However, these are not always specific to a certain disease, and instead most of them are commonly found in many of muscle diseases. Thus, muscle pathological findings should be carefully interpreted under the given clinical settings.

Multicenter Targeted Population Screening of Late Onset Pompe Disease in Unspecified Myopathy Patients in Korea

Background@#Pompe disease is a rare autosomal recessive disorder caused by the deficiency of a lysosomal enzyme, acid alpha-glucosidase (GAA). Early diagnosis and initiation of treatment with enzyme replacement therapy have remarkable effects on the prognosis of Pompe disease. We performed the expanded screening for late onset Pompe disease (LOPD) at eight centers in Korea. @*Methods@#From September 1, 2015, GAA activity were measured from both dried blood spot (DBS) and mixed leukocyte for 188 available patients. For 12 patients with low GAA activity, we performed Sanger sequencing of GAA gene. @*Results@#Among 188 patients, 115 were males. The mean of age of symptom onset and diagnosis were 34.3 years and 41.6 years. Among 12 patients with decreased GAA activity, two patients were confirmed to have LOPD with genetic test (c.1316T>A [p.M439K] + c.2015G>A [p.R672Q], c.1857C>G [p.S619R] + c.546G>C [leaky splicing]). Other two patients had homozygous G576S and E689K mutation, known as pseudodeficiency allele. @*Conclusions@#This study is expanded study of LOPD screening for targeted Korean population. We found two patients with LOPD, and the detection rate of LOPD is 1.06%. With application of modified GAA cutoff value (0.4), which was previously reported, there were no false positive results of GAA activity test using DBS. Therefore, it could be an appropriate screening test for LOPD in especially East-Asian population, in which pseudodeficiency allele is frequent.

Multicenter Targeted Population Screening of Late Onset Pompe Disease in Unspecified Myopathy Patients in Korea

Background@#Pompe disease is a rare autosomal recessive disorder caused by the deficiency of a lysosomal enzyme, acid alpha-glucosidase (GAA). Early diagnosis and initiation of treatment with enzyme replacement therapy have remarkable effects on the prognosis of Pompe disease. We performed the expanded screening for late onset Pompe disease (LOPD) at eight centers in Korea. @*Methods@#From September 1, 2015, GAA activity were measured from both dried blood spot (DBS) and mixed leukocyte for 188 available patients. For 12 patients with low GAA activity, we performed Sanger sequencing of GAA gene. @*Results@#Among 188 patients, 115 were males. The mean of age of symptom onset and diagnosis were 34.3 years and 41.6 years. Among 12 patients with decreased GAA activity, two patients were confirmed to have LOPD with genetic test (c.1316T>A [p.M439K] + c.2015G>A [p.R672Q], c.1857C>G [p.S619R] + c.546G>C [leaky splicing]). Other two patients had homozygous G576S and E689K mutation, known as pseudodeficiency allele. @*Conclusions@#This study is expanded study of LOPD screening for targeted Korean population. We found two patients with LOPD, and the detection rate of LOPD is 1.06%. With application of modified GAA cutoff value (0.4), which was previously reported, there were no false positive results of GAA activity test using DBS. Therefore, it could be an appropriate screening test for LOPD in especially East-Asian population, in which pseudodeficiency allele is frequent.

Hereditary Myopathy with Early Respiratory Failure with a Heterozygous TTN Gene Missense Mutation

Hereditary myopathy with early respiratory failure (HMERF) is characterized by early respiratory insufficiency which is inappropriate to the degree of limb muscle weakness. Recently, mutation in TTN gene was found in HMERF patients with the aid of gene sequencing. We describe the first case presenting with distal leg weakness and early respiratory failure confirmed by TTN gene mutation in Korea.

Progression of GNE Myopathy Based on the Patient-Reported Outcome

BACKGROUND AND PURPOSE: GNE myopathy is a rare progressive myopathy caused by biallelic mutations in the GNE gene, and frequently accompanied by rimmed vacuoles in muscle pathology. The initial symptom of foot drop or hip-girdle weakness eventually spreads to all limbs over a period of decades. Recent advances in pathophysiologic research have facilitated therapeutic trials aimed at resolving the core biochemical defect. However, there remains unsettled heterogeneity in its natural course, which confounds the analysis of therapeutic outcomes. We performed the first large-scale study of Korean patients with GNE myopathy. METHODS: We gathered the genetic and clinical profiles of 44 Korean patients with genetically confirmed GNE myopathy. The clinical progression was estimated retrospectively based on a patient-reported questionnaire on the status of the functional joint sets and daily activities. RESULTS: The wrist and neck were the last joints to lose antigravity functionality irrespective of whether the weakness started from the ankle or hip. Two-thirds of the patients could walk either independently or with an aid. The order of losing daily activities could be sorted from standing to eating. Patients with limb-girdle phenotype showed an earlier age at onset than those with foot-drop onset. Patients with biallelic kinase domain mutations tended to progress more rapidly than those with epimerase and kinase domain mutations. CONCLUSIONS: The reported data can guide the clinical management of GNE myopathy, as well as provide perspective to help the development of clinical trials.

A Family of Bethlem Myopathy Caused by a Heterozygous COL6A1 Mutation

Collagen-VI-related myopathies are caused by mutations in the COL6A1, COL6A2, and COL6A3 and are known to have a wide phenotypic spectrum, including Bethlem myopathy, Ullrich congenital muscular dystrophy, intermediate phenotype, and limb-girdle muscular dystrophy. These patients present with joint hyperextensibility and/or contractures as well as skin changes and muscle weakness, and so clinicians need to notice those extramuscular symptoms in order to achieve a correct diagnosis. We describe the clinical, pathological, and radiological features in a family with Bethlem myopathy caused by a COL6A1 mutation.

Myotonia Congenita Can Be Mistaken as Paroxysmal Kinesigenic Dyskinesia

No abstract available.

Characteristics of South Korean Patients with Hereditary Transthyretin Amyloidosis

BACKGROUND AND PURPOSE: This retrospective cross-sectional study included 18 patients from unrelated families harboring mutations of the transthyretin gene (TTR), and analyzed their characteristics and geographical distribution in South Korea. METHODS: The included patients had a diagnosis of systemic amyloidosis, clinical symptoms, such as amyloid neuropathy or cardiomyopathy, and confirmation of a TTR gene mutation using genetic analysis recorded between April 1995 and November 2014. RESULTS: The mean age at disease onset was 49.6 years, and the mean disease duration from symptom onset to diagnosis was 3.67 years. Fifteen of the 18 patients were classified as mixed phenotype, 2 as the neurological phenotype, and only 1 patient as the cardiac phenotype. The most-common mutation pattern in South Korea was Asp38Ala, which was detected in eight patients. Thirteen patients reported their family hometowns, and five of the eight harboring the Asp38Ala mutation were from the Gyeongsang province in southeast Korea. The other eight patients exhibited a widespread geographical distribution. A particularly noteworthy finding was that the valine at position 30 (Val30Met) mutation, which was previously reported as the most-common TTR mutation worldwide and also the most common in the Japanese population, was not detected in the present South Korean patients. CONCLUSIONS: South Korean patients with hereditary TTR amyloidosis exhibited heterogeneous TTR genotypes and clinical phenotypes. The findings of this study suggest that the distribution of TTR amyloidosis in South Korea is due to de novo mutations and/or related to the other countries in East Asia.

Reduction Plan of ‘Undeterminable’ in the Unexpected Antibody Screening by the Microcolumn Agglutination Automated Instrument / 대한수혈학회지

BACKGROUND: Among the results of an unexpected antibody screening test using IH-1000, ‘undeterminable’ results can be obtained. Repeated tests not only use reagents and consumables but also cause a turnaround time delay. Therefore, it is important to reduce the ‘undeterminable’ results and to determine the effects. METHODS: From January to early June, 2016, 2,872 cases/259,455 tests (1.11%) of ‘undeterminable’ were detected in the screening test. The factors considered to affect the ‘undeterminable’ were classified into four categories: ① reagent, ② consumables, ③ inspection environment & specimen, and ④ enhancing the equipment management. For data comparison, a chi-square test was conducted (95% confidence interval, 0.05 significant level). RESULTS: The incidence of ‘undeterminable’ cases decreased from 1.11% before management to 0.66% (P < 0.001) after Pool Cells management. The consumption of ‘LISS/Coombs Card’ decreased from 1.07% before management to 0.51% (P < 0.001) after management. By maintaining a clean inspection environment and strengthening sample management, the rate decreased from 1.11% before management to 0.66% (P < 0.001) after management. On the other hand, there was no difference in the incidence of ‘undeterminable’ between before and after IH-1000 management reinforcement. CONCLUSION: Among the factors predicted to affect the decrease in the incidence of ‘undeterminable’, the management of Pool Cells and keeping the inspection environment clean as well as improving sample management contributed the most to the reduced ‘undeterminable’. Improvements in the management of consumables, and removing dust from the inside of the equipment, had a positive impact. A continuous quality improvement theme has been adopted and it is helpful for managing and improving the predicted factors.

Electrophysiological characteristics of R47W and A298T mutations in CLC-1 of myotonia congenita patients and evaluation of clinical features

Myotonia congenita (MC) is a genetic disease that displays impaired relaxation of skeletal muscle and muscle hypertrophy. This disease is mainly caused by mutations of CLCN1 that encodes human skeletal muscle chloride channel (CLC-1). CLC-1 is a voltage gated chloride channel that activates upon depolarizing potentials and play a major role in stabilization of resting membrane potentials in skeletal muscle. In this study, we report 4 unrelated Korean patients diagnosed with myotonia congenita and their clinical features. Sequence analysis of all coding regions of the patients was performed and mutation, R47W and A298T, was commonly identified. The patients commonly displayed transient muscle weakness and only one patient was diagnosed with autosomal dominant type of myotonia congenita. To investigate the pathological role of the mutation, electrophysiological analysis was also performed in HEK 293 cells transiently expressing homo- or heterodimeric mutant channels. The mutant channels displayed reduced chloride current density and altered channel gating. However, the effect of A298T on channel gating was reduced with the presence of R47W in the same allele. This analysis suggests that impaired CLC-1 channel function can cause myotonia congenita and that R47W has a protective effect on A298T in relation to channel gating. Our results provide clinical features of Korean myotonia congenita patients who have the heterozygous mutation and reveal underlying pathophyological consequences of the mutants by taking electrophysiological approach.

Experience of Rh & Others Antigen Negative Rate Elicitation in a Blood Laboratory Center / 대한수혈학회지

BACKGROUND: The demand for Rh-related and other specific antigen negative donations has increased recently, and in response, we need to improve work efficiency while decreasing reagent consumption. Thus, we desire to create a ‘table of Nambu Blood Laboratory Center's own Rh-related and other antigen negative rate’. METHODS: We analyzed the results of Rh-related specific antigen test for 2,806,330 donors using ‘PK-7300’ and the results of manual test for 10,024 other blood type antigen-related specific and compound antigens. We made a table summarizing the results using two cases. RESULTS: The negative rate of Rh-related specific antigens was approximately 12.9% for C, 41.7% for c, 49.5% for E, and 9.2% for e antigens. The negative rate of compound antigens was increased when compared with the number of inspections. The negative rate for C and e antigens was increased from 90.1% to 97.3%, and that for E, c, and JKa was increased from 7.6% to 31.6%. CONCLUSION: The negative rate table made in July 2016 has been determined to be very effective in screening for specific and compound antigen negative blood. Also it was very efficient in terms of examining and supplying the compound antigen negative blood. It would be helpful to improve the supply of specific antigen negative blood to better meet the unique needs of each medical institution.

A family with dynamin 2-related centronuclear myopathy without ocular involvement

Centronuclear myopathy (CNM) is a rare congenital myopathy that is pathologically characterized by the centrally locatednuclei in most of the muscle fibers. On clinical examination, dynamin 2 (DNM2)-related CNM typically shows distaldominant muscle atrophy, ptosis, ophthalmoplegia, and contracture. The reported cases of CNM in Caucasian studies showa high prevalence rate of early-onset ptosis and ophthalmoplegia and correlated with the severity of the disease. However,Asian reports show a low prevalence and late-onset ocular symptoms in DNM2-related CNM patients. p.R465W is one ofthe most commonly found mutations in Western countries, and all the cases showed ocular symptoms. The proband and hisdaughter had no ocular symptoms despite harboring the same p.R465W mutation. This family makes us speculate that ocularsymptoms in DNM2-related CNM are influenced by ethnic background. In addition, this is the first familial case of DNM2-related CNM in Korea.

Right Cerebellopontine Angle Tumor Localized by Blink Reflex Abnormality

No abstract available.

Right Cerebellopontine Angle Tumor Localized by Blink Reflex Abnormality

No abstract available.

Ross Syndrome with Segmental Anhidrosis and Anisocoria: Application of Finger Winkle Test

Ross syndrome is characterized by a triad of segmental anhidrosis, tonic pupil, and generalized areflexia. Selective postganglionic autonomic denervation could be the differential diagnostic point for other diseases of the autonomic nervous system. Here we report a patient with regional anhidrosis in his left hand and sole, and anisocoria. An evaluation of sweating and the pupillary response together with generalized areflexia confirmed the diagnosis of Ross syndrome. The finger wrinkle test is a simple and useful tool for revealing segmental sympathetic denervation.

Merosin-Deficient Congenital Muscular Dystrophy with Polymicrogyria and Subcortical Heterotopia: A Case Report

This paper reports the brain magnetic resonance imaging (MRI) findings of a case of merosin-deficient congenital muscular dystrophy (MDCMD) in a neonate and discusses the spectrum of brain involvement in MDCMD. A neonate presented hypotonia, increased serum creatine kinase levels, and polymicrogyria and subcortical heterotopia on brain MRI involving both posterior temporal and occipital lobes. Although these findings suggested Fukuyama muscular dystrophy, muscle biopsy showed dystrophic changes and an absence of merosin staining. We found that compound heterozygous mutation for c.2049_2050delAG (p.R683fs) and c.5866-2A>G in the LAMA2 gene which encodes Laminin-α2. To our knowledge, this is the second Korean case of MDCMD with polymicrogyria and subcortical heterotopias. This case shows that a range of brain structural malformations can be found in children with MDCMD and that the classification of congenital muscular dystrophy (CMD) is not complete yet, as indicated previously in reports suggesting other unclassified forms of CMD.

Cap Myopathy With a Heterozygous TPM3 Missense Mutation

Cap myopathy is pathologically characterized by cap structures comprising well-demarcated areas under the sarcolemma and containing deranged myofibrils and scattered Z-disks. Clinically it presents with slowly progressive muscle weakness, myopathic face, and frequent respiratory insufficiency. Four genes have been reported to be associated with the disease: TPM2, TPM3, ACTA1, and NEB. Here we describe that a patient presenting with mild limb weakness with facial affection showed cap structures on muscle pathology and carried a heterozygous TPM3 mutation.