RESUMEN
A 25-year-old woman presented with 1 year of progressive orthopnoea, initially explained as bilateral diaphragmatic paresis caused by seronegative myasthenia gravis. She required assisted ventilation and received pyridostigmine and corticosteroids. She had minimal (particularly proximal) symmetrical tetraparesis with apparent bilateral diaphragmatic weakness, but had normal sensation. Further investigation suggested an overlap myositis with shrinking lung syndrome from systemic lupus erythematosus. She improved following immunosuppression with pulse corticosteroids and rituximab, and at 3 months no longer needed bilevel positive airway pressure support.
Asunto(s)
Lupus Eritematoso Sistémico , Parálisis Respiratoria , Humanos , Femenino , Adulto , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Parálisis Respiratoria/etiología , Parálisis Respiratoria/diagnóstico , Diagnóstico Diferencial , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/diagnósticoRESUMEN
Tubular aggregate myopathies comprise a rare group of disorders with characteristic pathological findings and heterogeneous phenotypes, including myasthenic syndrome. We describe a patient with tubular aggregate myopathy who presented with fatiguable weakness improving with pyridostigmine, respiratory involvement and possible cardiac manifestations. We highlight the utility of muscle biopsy in atypical myasthenic syndrome.
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Enfermedades Autoinmunes , Miopatías Estructurales Congénitas , Humanos , Músculo Esquelético/patología , Debilidad Muscular/etiología , Debilidad Muscular/patología , Miopatías Estructurales Congénitas/complicaciones , Miopatías Estructurales Congénitas/genética , Miopatías Estructurales Congénitas/patología , FenotipoRESUMEN
A 40-year-old woman presented with a 20 kg weight loss and asymmetrical hip and shoulder girdle muscle weakness; she had a raised serum creatine kinase and mild peripheral blood eosinophilia. There was no evidence of a parasitic infection or vasculitis. A muscle biopsy showed eosinophilic myositis. Following treatment with oral corticosteroid, methotrexate and intravenous immunoglobulin infusion, her weakness initially mildly improved and her serum creatine kinase reduced. However, despite continued immunosuppression her condition progressed over 3 years. The pattern of muscle weakness suggested a muscular dystrophy. Genetic testing confirmed heterozygous calpain mutations consistent with limb girdle muscular dystrophy type 2A.
RESUMEN
Introduction: Haycocknema perplexum is an exceedingly rare cause of parasitic myositis endemic to Australia, more specifically, Tasmania and North Queensland. There is a paucity of literature regarding this diagnosis, with only nine previously described cases. Diagnosis: This report details two cases of biopsy-confirmed H. perplexum myositis from Townsville University Hospital and describes the first-ever case of subclinical infection. There is limited known information regarding the H. perplexum life cycle and a definitive host which has hindered the development of a non-invasive diagnostic test. A review of the previously described cases has identified the hallmark features of this enigmatic condition: a triad of serological markers including deranged hepatic function, persistent eosinophilia and an elevated creatine kinase. Conclusions: This report aimed to raise awareness of H. perplexum myositis and the possibility of subclinical infection, which suggests a protracted disease course. Further research is required to identify a non-invasive diagnostic test, given that early diagnosis and timely initiation of albendazole treatment may drastically limit patient disability.
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Esclerosis Amiotrófica Lateral/patología , Fibras Musculares Esqueléticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/fisiopatología , Creatina Quinasa/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/patología , Estudios Retrospectivos , Capacidad VitalRESUMEN
Metabolic myopathies are a diverse group of rare genetic disorders and their associated muscle symptoms may be subtle. Patients may present with indolent myopathic features, exercise intolerance or recurrent rhabdomyolysis. Diagnostic delays are common and clinicians need a high index of suspicion to recognise and differentiate metabolic myopathies from other conditions that present in a similar fashion. Standard laboratory tests may be normal or non-specific, particularly between symptomatic episodes. Targeted enzyme activity measurement and next-generation genetic sequencing are increasingly used. There are now specific enzyme replacement therapies available, and other metabolic strategies and gene therapies are undergoing clinical trials. Here, we discuss our approach to the adult patient with suspected metabolic myopathy. We outline key features in the history and examination and discuss some mimics of metabolic myopathies. We highlight some disorders of glycogen and fatty acid utilisation that present in adulthood and outline current recommendations on management.
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Enfermedades Metabólicas/complicaciones , Enfermedades Musculares/complicaciones , Humanos , Enfermedades Metabólicas/metabolismo , Enfermedades Musculares/metabolismoAsunto(s)
Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/patología , Proteínas Asociadas a Matriz Nuclear/genética , Enfermedades Faríngeas/genética , Enfermedades Faríngeas/patología , Proteínas de Unión al ARN/genética , Disfunción de los Pliegues Vocales/genética , Disfunción de los Pliegues Vocales/patología , Adulto , Edad de Inicio , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Neurona Motora/complicaciones , Mutación/genética , Linaje , Enfermedades Faríngeas/complicaciones , Fenotipo , Disfunción de los Pliegues Vocales/complicacionesRESUMEN
A 70-year-old man presented with respiratory distress and proximal muscle weakness shortly after biopsy of a left forearm mass. The biopsy showed giant cell myositis, and serological investigations identified a grossly elevated serum creatine kinase level, suggesting skeletal muscle damage. Serum troponin T was also high, but troponin I was normal. Serum antiacetylcholine receptor antibodies were positive, and imaging showed a thymoma. He recovered well following intravenous immunoglobulin and corticosteroids, and later underwent thymectomy. He is currently in sustained remission, with no clinically detectable myasthenia, but subsequently, developed hypogammaglobulinaemia. Neurologists should remember giant cell myositis/myocarditis can occur in patients who have myasthenia gravis with thymoma, as it is potentially fatal, but may respond to immunosuppression.
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Corticoesteroides/uso terapéutico , Células Gigantes/patología , Inmunoglobulinas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Miositis/tratamiento farmacológico , Anciano , Humanos , Imagen por Resonancia Magnética , Masculino , Músculo Esquelético/patología , Miositis/patología , Traumatismos de los Tejidos BlandosRESUMEN
BACKGROUND: Autosomal dominant (AD) central core disease (CCD) is a congenital myopathy characterised by the presence of cores in the muscle fibres which correspond to broad areas of myofibrils disorganisation, Z-line streaming and lack of mitochondria. Heterozygous mutations in the RYR1 gene were observed in the large majority of AD-CCD families; however, this gene was excluded in some of AD-CCD families. OBJECTIVE: To enlarge the genetic spectrum of AD-CCD demonstrating mutations in an additional gene. PATIENTS AND METHODS: Four affected AD family members over three generations, three of whom were alive and participate in the study: the mother and two of three siblings. The symptoms began during the early childhood with mild delayed motor development. Later they developed mainly tibialis anterior weakness, hypertrophy of calves and significant weakness (amyotrophic) of quadriceps. No cardiac or ocular involvement was noted. RESULTS: The muscle biopsies sections showed a particular pattern: eccentric cores in type 1 fibres, associated with type 1 predominance. Most cores have abrupt borders. Electron microscopy confirmed the presence of both unstructured and structured cores. Exome sequencing analysis identified a novel heterozygous missense mutation p.Leu1723Pro in MYH7 segregating with the disease and affecting a conserved residue in the myosin tail domain. CONCLUSIONS: We describe MYH7 as an additional causative gene for AD-CCD. These findings have important implications for diagnosis and future investigations of AD-congenital myopathies with cores, without cardiomyopathy, but presenting a particular involvement of distal and quadriceps muscles.
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Miosinas Cardíacas/genética , Predisposición Genética a la Enfermedad/genética , Mutación Missense/genética , Miopatía del Núcleo Central/genética , Cadenas Pesadas de Miosina/genética , Adulto , Anciano , Femenino , Heterocigoto , Humanos , Masculino , Fibras Musculares de Contracción Lenta/diagnóstico por imagen , Fibras Musculares de Contracción Lenta/patología , Fibras Musculares de Contracción Lenta/ultraestructura , Miopatía del Núcleo Central/diagnóstico por imagen , Miopatía del Núcleo Central/patología , Linaje , RadiografíaRESUMEN
OBJECTIVE: Titin gene (TTN) mutations have been described in eight families with hereditary myopathy with early respiratory failure (HMERF). Some of the original patients had features resembling myofibrillar myopathy (MFM), arguing that TTN mutations could be a much more common cause of inherited muscle disease, especially in presence of early respiratory involvement. METHODS: We studied 127 undiagnosed patients with clinical presentation compatible with MFM. Sanger sequencing for the two previously described TTN mutations in HMERF (p.C30071R in the 119th fibronectin-3 (FN3) domain, and p.R32450W in the kinase domain) was performed in all patients. Patients with mutations had detailed review of their clinical records, muscle MRI findings and muscle pathology. RESULTS: We identified five new families with the p.C30071R mutation who were clinically similar to previously reported cases, and muscle pathology demonstrated diagnostic features of MFM. Two further families had novel variants in the 119th FN3 domain (p.P30091L and p.N30145K). No patients were identified with mutations at position p.32450. CONCLUSIONS: Mutations in TTN are a cause of MFM, and titinopathy is more common than previously thought. The finding of the p.C30071R mutation in 3.9% of our study population is likely due to a British founder effect. The occurrence of novel FN3 domain variants, although still of uncertain pathogenicity, suggests that other mutations in this domain may cause MFM, and that the disease is likely to be globally distributed. We suggest that HMERF due to mutations in the TTN gene be nosologically classified as MFM-titinopathy.
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Conectina/genética , Efecto Fundador , Enfermedades Genéticas Congénitas/genética , Enfermedades Musculares/genética , Insuficiencia Respiratoria/genética , Adulto , Anciano , Femenino , Enfermedades Genéticas Congénitas/patología , Haplotipos , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético/patología , Enfermedades Musculares/patología , Mutación , Linaje , Reacción en Cadena de la Polimerasa , Insuficiencia Respiratoria/patologíaRESUMEN
BACKGROUND: A newly defined congenital myasthenic syndrome (CMS) caused by DPAGT1 mutations has recently been reported. While many other CMS-associated proteins have discrete roles localised to the neuromuscular junction, DPAGT1 is ubiquitously expressed, modifying many proteins, and as such is an unexpected cause of isolated neuromuscular involvement. METHODS: We present detailed clinical characteristics of five patients with CMS caused by DPAGT1 mutations. RESULTS: Patients have prominent limb girdle weakness and minimal craniobulbar symptoms. Tubular aggregates on muscle biopsy are characteristic but may not be apparent on early biopsies. Typical myasthenic features such as pyridostigmine and 3, 4- diaminopyridine responsiveness, and decrement on repetitive nerve stimulation are present. CONCLUSIONS: These patients mimic myopathic disorders and are likely to be under-diagnosed. The descriptions here should facilitate recognition of this disorder. In particular minimal craniobulbar involvement and tubular aggregates on muscle biopsy help to distinguish DPAGT1 CMS from the majority of other forms of CMS. Patients with DPAGT1 CMS share similar clinical features with patients who have CMS caused by mutations in GFPT1, another recently identified CMS subtype.