Assuntos
Meningite Pneumocócica , Vasculite do Sistema Nervoso Central , Humanos , Meningite Pneumocócica/complicações , Meningite Pneumocócica/diagnóstico , Meningite Pneumocócica/tratamento farmacológico , Vasculite do Sistema Nervoso Central/complicações , Vasculite do Sistema Nervoso Central/diagnóstico por imagem , Infarto CerebralRESUMO
OBJECTIVE: In 2012, a large number of myositis cases with anti-mitochondrial M2 (AMA-M2) antibody, which had well been known as the serological hallmark for primary biliary cholangitis (PBC), were reported in Japan. Recently, some case series from Japan, France, America, China and India have shown that approximately 2.5% to 19.5% of patients with myositis have AMA-M2 antibody. The objective of this study was to clarify the prevalence, clinical features, treatment outcome, and severity determinants of AMA-M2 positive myositis. METHODS: This study was a multicenter observational study. We enrolled patients who were diagnosed with myositis during a ten-year period between 2012 and 2021. RESULTS: Of the total of 185 patients with inflammatory myopathy, 17 patients were positive for AMA-M2 antibody. The typical symptoms were weakness mainly involving paravertebral muscles, weight loss, respiratory failure, and cardiac complications. Thirteen of the 17 patients had cardiac complications. A strong correlation was found between respiratory failure and modified Rankin Scale (mRS) score. A strong correlation was also found between respiratory failure and body weight, indicating that weight loss can be an indicator of potential progression of respiratory failure. Six of the 17 patients were complicated by malignancy. CONCLUSIONS: This study showed significant correlations between % vital capacity (VC), body mass index (BMI), and mRS score in patients with AMA-M2-positive myositis. Immunotherapy often improved CK level and respiratory dysfunction. We therefore propose that %VC and BMI should be monitored as disease indicators in treatment of AMA-M2-positive myositis.
Assuntos
Cirrose Hepática Biliar , Miosite , Insuficiência Respiratória , Humanos , Cirrose Hepática Biliar/diagnóstico , Autoanticorpos , Miosite/diagnóstico , Miosite/terapia , Redução de PesoRESUMO
Oculopharyngodistal myopathy (OPDM) is an adult-onset inherited neuromuscular disorder characterized by progressive ptosis, external ophthalmoplegia, and weakness of the masseter, facial, pharyngeal, and distal limb muscles. The myopathological features are presence of rimmed vacuoles (RVs) in the muscle fibers and myopathic changes of differing severity. Inheritance is variable, with either putative autosomal-dominant or autosomal-recessive pattern. Here, using a comprehensive strategy combining whole-genome sequencing (WGS), long-read whole-genome sequencing (LRS), linkage analysis, repeat-primed polymerase chain reaction (RP-PCR), and fluorescence amplicon length analysis polymerase chain reaction (AL-PCR), we identified an abnormal GGC repeat expansion in the 5' UTR of GIPC1 in one out of four families and three sporadic case subjects from a Chinese OPDM cohort. Expanded GGC repeats were further confirmed as the cause of OPDM in an additional 2 out of 4 families and 6 out of 13 sporadic Chinese individuals with OPDM, as well as 7 out of 194 unrelated Japanese individuals with OPDM. Methylation, qRT-PCR, and western blot analysis indicated that GIPC1 mRNA levels were increased while protein levels were unaltered in OPDM-affected individuals. RNA sequencing indicated p53 signaling, vascular smooth muscle contraction, ubiquitin-mediated proteolysis, and ribosome pathways were involved in the pathogenic mechanisms of OPDM-affected individuals with GGC repeat expansion in GIPC1. This study provides further evidence that OPDM is associated with GGC repeat expansions in distinct genes and highly suggests that expanded GGC repeat units are essential in the pathogenesis of OPDM, regardless of the genes in which the expanded repeats are located.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Distrofias Musculares/genética , Adolescente , Adulto , Povo Asiático/genética , Cromossomos Humanos Par 19/genética , Metilação de DNA , Feminino , Humanos , Escore Lod , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Distrofias Musculares/patologia , Distrofias Musculares/fisiopatologia , Linhagem , RNA-Seq , Expansão das Repetições de Trinucleotídeos/genética , Proteína Supressora de Tumor p53/metabolismo , Adulto JovemRESUMO
PURPOSE: Plasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females. METHODS: Between 1 July 2014 and 31 December 2015, we screened 2,359 patients (1,324 males) referred from 168 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively. RESULTS: Of 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml-1) and low α-Gal A activity (≤4.0 nmol h-1 ml-1), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 14 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 7 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance). CONCLUSION: Plasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.
Assuntos
Biomarcadores/sangue , Doença de Fabry/sangue , Testes Genéticos , Glicolipídeos/sangue , Esfingolipídeos/sangue , Idoso , Doença de Fabry/genética , Doença de Fabry/patologia , Feminino , Galactosidases/sangue , Galactosidases/genética , Glicolipídeos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Seleção de Pacientes , Fatores de Risco , Esfingolipídeos/genéticaRESUMO
OBJECTIVE: This study was to clarify the neuropathological findings of acute encephalomyelopathy with Sjögren's syndrome. METHODS: We examined an autopsied case of acute encephalomyelopathy with Sjögren's syndrome. CASE REPORT: A 40-year-old woman developed acute myelopathy and brainstem dysfunction. Magnetic resonance imaging (MRI) revealed high-intensity lesions on T2-weighted axial images (T2WI) in the medulla oblongata and cervical spinal cord. We established a diagnosis of Sjögren's syndrome (SjS) according to the European Community criteria. The patient was treated with intravenous methylprednisolone (500 mg/day) for three days, followed by oral prednisolone. Although her neurological symptoms improved, her general condition deteriorated after the onset of acute colonic pseudo-obstruction and she died of multiple organ failure associated with hemophagocytosis. RESULTS: Autopsy showed atrophy of the secretory glands and an accumulation of lymphocytes around the ducts, confirming the diagnosis of Sjögren's syndrome. Neuropathological examination revealed multifocal lesions in the cervical spinal cord and medulla, along with scattered perivascular lymphocytic infiltration. In addition, there was demyelination, spongy change and axonal swelling in the white matter, but no remarkable vasculitic changes were seen in the central nervous system. CONCLUSION: Although the steroid therapy may have had a significant influence, the main pathological finding in this case was not vasculitis, but rather axonal degeneration with spongy change and axonal swelling.
Assuntos
Doenças do Sistema Nervoso Central/etiologia , Doenças do Sistema Nervoso Central/patologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/patologia , Adulto , Autopsia , Tronco Encefálico/patologia , Feminino , Humanos , Pseudo-Obstrução Intestinal/etiologia , Linfo-Histiocitose Hemofagocítica/etiologia , Imageamento por Ressonância Magnética , Insuficiência de Múltiplos Órgãos/etiologia , Prednisolona/uso terapêutico , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico , Medula Espinal/patologiaRESUMO
BACKGROUND: Emery-Dreifuss muscular dystrophy, caused by EMD gene mutations, is characterized by humeroperoneal muscular dystrophy, joint contractures, and conduction defects and is often associated with sudden cardiac death, even without prior cardiac symptoms. OBJECTIVE: To describe the clinical and molecular features of 2 patients with limb-girdle muscular dystrophy with mutations in EMD. DESIGN: Case reports. SETTING: Academic research. PATIENTS: Two male patients manifested proximal dominant muscle involvement, with minimal or no joint and cardiac involvement. MAIN OUTCOME MEASURES: Muscle biopsy and mutation analysis results. RESULTS: Immunohistochemistry revealed an absence of emerin staining in muscle biopsy specimens. Mutation analysis identified nonsense mutations in EMD. CONCLUSIONS: Mutations in EMD may indicate a limb-girdle muscular dystrophy phenotype. Identification of emerin deficiency among patients with limb-girdle muscular dystrophy is essential to prevent cardiac catastrophe.