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Late-onset Pompe disease manifests predominantly in the proximal lower limbs and may be mistaken for an inflammatory myopathy. A 46-year-old man with acromegaly had an 8-year history of progressive weakness. His myopathy was initially attributed to the acromegaly, but severe progression prompted a muscle biopsy, which suggested an inflammatory myopathy. However, his weakness progressed despite treatment for polymyositis. His muscle ultrasound scan pattern was more suggestive of Pompe disease than polymyositis, and Pompe disease was confirmed by genetic and enzymatic testing. Patients with apparent polymyositis, which persists despite treatment, require reconsideration of the diagnosis, with particular attention to treatable genetic causes.

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Allgrove syndrome is an autosomal recessive disease mostly caused by mutations in the AAAS gene. It has variable clinical features but its cardinal features comprise the triad of achalasia, alacrimia and adrenal insufficiency. It typically develops during the first decade of life, but some cases have second and third decades onset. We describe a 25-year-old woman with Allgrove syndrome who had progressive amyotrophy, achalasia, dry eyes and adrenal insufficiency since childhood. Awareness of its neurological manifestations and multisystem features helps to shorten the time for diagnosis and allow appropriate symptomatic treatment.

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INTRODUCTION: Cardiopulmonary exercise testing (CPET) is increasingly used to determine aerobic fitness in health and disability conditions. Patients with neuromuscular diseases (NMDs) often present with symptoms of cardiac and/or skeletal muscle dysfunction and fatigue that might impede the ability to deliver maximal cardiopulmonary effort. Although an increasing number of studies report on NMDs' physical fitness, the applicability of CPET remains largely unknown. AREAS COVERED: This systematic review synthesized evidence about the quality and feasibility of CPET in NMDs and patient's aerobic fitness. The review followed the PRISMA guidelines (PROSPERO number CRD42020211068). Between September and October 2020 one independent reviewer searched the PubMed/MEDLINE, EMBASE, SCOPUS, and Web of Science databases. Excluding reviews and protocol description articles without baseline data, all study designs using CPET to assess adult or pediatric patients with NMDs were included. The methodological quality was assessed according to the American Thoracic Society/American College of Chest Physicians (ATS/ACCP) recommendations. EXPERT OPINION: CPET is feasible for ambulatory patients with NMDs when their functional level and the exercise modality are taken into account. However, there is still a vast potential for standardizing and designing disease-specific CPET protocols for patients with NMDs. Moreover, future studies are urged to follow the ATS/ACCP recommendations.

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Immune-mediated necrotising myopathy is a rare autoimmune myopathy characterised by severe progressive muscle weakness, elevated levels of creatine kinase (CK), and necrosis with minimal inflammatory cell infiltration on muscle biopsy. We report a case of a previously healthy 42-year-old woman who presented with progressive muscle weakness 2 weeks after immunisation for yellow fever, tetanus/diphtheria and hepatitis B. Her symptoms started from the lower limbs and progressed to the upper limbs and cervical region associated with dysphagia, making her wheelchair bound. Electromyography showed a myopathic pattern, with a CK level of 12.177 U/L (reference value: 26-190 U/L), and biceps brachial muscle biopsy confirmed necrosis and regeneration fibres. The immunoblot test was positive for antisignal recognition particle. She was successfully treated with prednisone (1 mg/kg/day). Although considered safe, vaccines may cause allergic reactions or trigger autoimmune disorders. Currently, a causal relationship between them cannot be established.

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OBJECTIVE: To deep sequence the TRIM33 gene in tumours from patients with cancer-associated anti-TIF1γ autoantibody-positive dermatomyositis (DM) as TRIM33 somatic mutations in tumours may trigger this auto-immune disease. METHODS: Next generation sequencing of tumour DNA samples from patients with cancer-associated anti-TIF1γ autoantibody-positive DM. Fourteen tumours from 13 anti-TIF1γ autoantibody-positive DM individuals were sequenced along with two control tumours from non-DM individuals. RESULTS: Fourteen probable somatic variants from four tumours were identified in the TRIM33 gene. CONCLUSION: These results are in accordance with the previous report of Pinal-Fernandez et al. and support the hypothesis of a role of TRIM33 gene mutations in the pathophysiology of anti-TIF1γ autoantibody-positive DM.

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The aim of this study was to examine the effects of storage on the quality of sausages made with breast from chickens affected by wooden breast myopathy (WBM). Breast samples from male broilers slaughtered at 48 days old were used. Normal (absence of myopathy), moderate degree (hardness only in one region of the breast) and severe degree samples (hardness over the entire length of the breast) were processed into sausages and evaluated prior to storage and after being vacuum-packed and stored for 7, 14, 21 and 28 days at 4 °C. There was a decrease (p < 0.001) in pH and an increase (p < 0.001) in cooking weight loss in samples of sausages, regardless of the myopathy, after 28 days of storage. Sausages produced with chicken breast samples affected by wooden breast myopathy presented higher (p < 0.0001) moisture concentration (72% for the severe degree) and higher (p = 0.0224) protein concentration (17.27% and 17.36%, respectively, for the moderate and severe degrees) than sausages made of normal samples (70.72% and 14.32%, respectively). The results indicate that sausages produced with meat from birds moderately and severely affected by the myopathy show higher oxidative stability. Fresh sausages produced with breast meat from birds affected by wooden breast syndrome may be stored (4 °C) for up to 28 days without exhibiting the characteristic rancid taste and smell. In sensory analysis, no differences were observed between the formulations, which suggests that the consumers approved the samples regardless of the disease severity in the meat used for the making of the sausages. The current results show that chicken meat affected by wooden breast myopathy can be used for producing fresh sausages in the industry.

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Subacute symmetrical proximal muscle weakness and persistent elevated creatine kinase levels are typical of immune-mediated necrotising myopathy (IMNM). These conditions are accompanied by copious myofibre necrosis, degeneration and regeneration with minimal to no inflammation on muscle biopsy. We report two cases (case 1 and case 2) of asymptomatic IMNM from different families with hyperCKaemia associated with positive anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, respectively, and we also reviewed the literature. There are only a few previous descriptions of patients with asymptomatic IMNM.The disease onset could be insidious and lead to delayed diagnosis and treatment. We recommend testing for the anti-HMGCR and anti-SRP antibodies in patients with idiopathic hyperCKaemia because they could show no symptoms of this disorder.

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Brief resolved unexplained events (BRUEs) have numerous and varied causes posing a challenge to investigation and management. A subset of infants with the neuromuscular disorder sodium channel myotonia, due to mutations in the SCN4A gene, experience apnoeic events due to laryngospasm (myotonia) of the upper airway muscles that may present as a BRUE. We sought to ascertain the frequency, severity and outcome of infants carrying the G1306E SCN4A mutation commonly associated with this presentation. We report 12 new cases of individuals with the G1306E mutation from three unrelated families and perform a literature review of all published cases. Infants with the G1306E mutation almost universally experience laryngospasm and apnoeic events. The severity varies significantly, spans both low and high-risk BRUE categories or can be more severe than criteria for a BRUE would allow. At least a third of cases require intensive care unit (ICU) care. Seizure disorder is a common erroneous diagnosis. Apnoeas are effectively reduced or abolished by appropriate treatment with anti-myotonic agents. Probands with the G1306E mutation who are family planning need to be counselled for the likelihood of post-natal complications. There is readily available and extremely effective treatment for the episodic laryngospasm and apnoea caused by this mutation. Proactively seeking clinical evidence of myotonia or muscle hypertrophy with consideration of CK and EMG in high risk BRUEs or more complex apnoeic events may reduce avoidable and prolonged ICU admissions, patient morbidity and potentially mortality.

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Tarantula's leg muscle thick filament is the ideal model for the study of the structure and function of skeletal muscle thick filaments. Its analysis has given rise to a series of structural and functional studies, leading, among other things, to the discovery of the myosin interacting-heads motif (IHM). Further electron microscopy (EM) studies have shown the presence of IHM in frozen-hydrated and negatively stained thick filaments of striated, cardiac, and smooth muscle of bilaterians, most showing the IHM parallel to the filament axis. EM studies on negatively stained heavy meromyosin of different species have shown the presence of IHM on sponges, animals that lack muscle, extending the presence of IHM to metazoans. The IHM evolved about 800 MY ago in the ancestor of Metazoa, and independently with functional differences in the lineage leading to the slime mold Dictyostelium discoideum (Mycetozoa). This motif conveys important functional advantages, such as Ca2+ regulation and ATP energy-saving mechanisms. Recent interest has focused on human IHM structure in order to understand the structural basis underlying various conditions and situations of scientific and medical interest: the hypertrophic and dilated cardiomyopathies, overfeeding control, aging and hormone deprival muscle weakness, drug design for schistosomiasis control, and conditioning exercise physiology for the training of power athletes.

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Antecedentes: El síndrome de Gorlin-Goltz, o síndrome nevoide de células básales (SNCB), es un trastorno autosómico dominante de baja incidencia. Su etiología se relaciona con una mutación en el gen PTCH y afecta los sistemas esquelético, oftalmológico y neurológico. Su prevalencia es de 1:60.000 y las mutaciones de novo se presentan aproximadamente en un 20 % a 30 % de los casos. Objetivo: Describir el proceso diagnóstico y manejo de un caso de esporádica presentación de una paciente con SNCB con carcinoma escamocelular (CEC) en labio superior. Descripción del caso: Se trató de una mujer de 58 años, quien asistió a consulta odontológica por motivos estéticos y funcionales. Se encontró un CEC (confirmado por inmunohistoquímica) asintomático delimitado en el lado izquierdo del labio superior, con erosiones de color rojizo y costra. No se encontraron linfoadenopatías asociadas. También evidenció fisuras palmoplantares y múltiples carcinomas basocelulares en la espalda y el dorso de la mano izquierda (con antecedentes familiares similares). Radiográficamente, no se observaron queratoquistes mandibulares que usualmente se asocian con el síndrome de Gorlin-Goltz. Conclusiones: Se diagnosticó SNCB en la paciente, pues presentaba dos criterios mayores (dos o más CBC y piqueteado palmoplantar) y dos menores (calcificación laminar de la hoz del cerebro y antecedente de fibromas ováricos). El tratamiento odontológico se planeó y se remitió a la paciente a la institución pertinente para manejar su condición sistémica.

Background: Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder with low incidence. The etiology' is associated with a PTCH gene mutation and affects the skeletal, ophthalmic and neurological systems. The prevalence is 1:60,000 and de novo mutations occur approximately in 20% to 30% of the cases. Objective: To describe the diagnosis and management process for a rare case of a NBCCS patient who developed squamous cell carcinoma (SCC) in the upper lip. Case Description: The patient is a 58 year-old woman who attended to the dental office for aesthetic and functional reasons. An asymptomatic SCC was found (confirmed after immunohistochemical evidence) with defined limits to the left of the upper lip. It showed reddish erosions and some scab. No associated lymphadenopathies were found. The patient had some plantar foot fissures and multiple carcinoma basal cells in the back and in the left hand dorsum (with similar family previous cases). No maxillary keratocyst were observed in the radiographs, notwithstanding they are always associated with the Gorlin-Goltz syndrome. Conclusions: The patient was diagnosed with NBCCS based on two main criteria (two or more SCC lesions and plantar foot fissures) and two mild criteria (laminar calcification in the cerebral falx and family background of ovarian fibromas). A dental treatment was designed, and the patient was referred to another institution for a systemic treatment of her disease.

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INTRODUCTION: MRI characterization of dysferlinopathy has been mostly limited to the lower limbs. We aimed to broaden the MRI description of dysferlinopathy and to correlate it with objective measures of motor dysfunction. METHODS: Sequential whole-body axial MRI was performed in 27 patients with genetically confirmed dysferlinopathy classified according to disease duration. Spearman correlations of fatty infiltration scores versus Motor Function Measure (MFM) were calculated. RESULTS: Significant fatty infiltration was symmetrically present in early stages mainly in the posterior compartments of legs and thighs, thigh adductors, pelvic girdle, and some paravertebral muscles and the subscapularis. Later, fatty infiltration involved leg and thigh anterior compartments, arms and forearms, paravertebral, and trunk muscles. MRI infiltration score correlated positively with disease duration and negatively with MFM scale. CONCLUSIONS: We expand MRI characterization of dysferlinopathy and provide evidence for use of MRI scoring combined with motor functional scales to assess the natural course of disease. Muscle Nerve, 2016 Muscle Nerve 54: 203-210, 2016.

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As miopatias em equinos são classificadas de acordo com aspectos clínicos, morfológicos e moleculares, em três grandes grupos: não associadas ao exercício, associadas ao exercício e devido alteração da condução elétrica do sarcolema. Apesar dos avanços no diagnóstico, a literatura ainda relata surtos de miopatia em equinos sem etiologia esclarecida em diversos países. O objetivo desse estudo foi descrever as alterações histológicas e histoquímicas de biópsias musculares de equinos acometidos por miopatia. Sete equinos da raça Quarto de Milha, com 18-24 meses de idade, apresentaram sinais clínicos de miopatia. Dentre esses animais, cinco apresentaram sinais subagudos leves a moderados e dois apresentaram sinais hiperagudos severos e decúbito lateral. Foram realizadas biópsias musculares utilizando a técnica percutânea, por agulha tipo Bergström, no músculo glúteo médio em todos os animais acometidos. As amostras foram processadas por meio de técnicas histológicas (HE, Tricrômio de Gomori modificado) e histoquímicas (PAS, NADH, ATPase). Nos quadros clínicos mais leves, a principal alteração encontrada foi a presença de fibras vermelhas rajadas do tipo I e IIA, que estão associadas às alterações do metabolismo oxidativo e das funções mitocondriais, como ocorrem nas miopatias mitocondriais. Também foram observadas fibras atróficas do tipo I e IIA, além da presença de agregados subsarcolemais. Nos quadros mais severos o tecido muscular apresentou infiltrado inflamatório, aumento de colágeno, fagocitose, necrose, calcificação e regeneração muscular. Diante dos achados morfológicos, da resposta à terapia com vitamina E e Se e da baixa mortalidade quando comparado aos relatos de miopatia atípica, conclui-se que esse surto foi desencadeado por lesões mitocondriais, caracterizadas pelas fibras musculares vermelhas rajadas, possivelmente devido uma quebra da homeostase de vitamina E e Se, sendo compatível com o diagnóstico de miopatia nutricional.

Equine myopathies are classified according clinic, morphologic and molecular features in three groups: Non-exertional, exertional, and abnormal muscle membrane conduction. In spite the advances in diagnostic, the literature has reported outbreaks of equine myopathy without clear etiology in several countries. The aim of this study was to describe the histological and histochemical findings of muscle biopsies in an outbreak of equine myopathy. Seven 18 to 24-month-old Quarter horses showed clinical signs of myopathy. Five horses presented mild clinical signs and two horses had severe clinical signs with recumbency. Muscle biopsies were obtained from gluteal medium muscle by percutaneous technique with Bergstrom needle in all affected horses. Muscle samples were processed by histological (HE, modified gomori-trichrome) and histochemical (PAS, NADH, ATPase) technics. In animals with mild clinical signs, ragged red fibers type I and IIA, related to the oxidative metabolism dysfunction of mitochondria, was the main abnormality found. Muscle fiber atrophy and presence of subsarcolemmal aggregates in type I and IIA muscle fibers were also observed. More severe affected horses presented inflammatory infiltrate, proliferation of collagen, phagocytosis, necrosis and calcification. Based on the morphological findings, vitamin E therapy response associated with the low mortality when compared with atypical myopathy reports, We concluded that this outbreak was triggering for mitochondrial lesions, characterized by ragged red muscle fibers, probably due a breakdown homeostasis in vitamin E and Se, being compatible with nutritional myopathy diagnosis.

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As miopatias em equinos são classificadas de acordo com aspectos clínicos, morfológicos e moleculares, em três grandes grupos: não associadas ao exercício, associadas ao exercício e devido alteração da condução elétrica do sarcolema. Apesar dos avanços no diagnóstico, a literatura ainda relata surtos de miopatia em equinos sem etiologia esclarecida em diversos países. O objetivo desse estudo foi descrever as alterações histológicas e histoquímicas de biópsias musculares de equinos acometidos por miopatia. Sete equinos da raça Quarto de Milha, com 18-24 meses de idade, apresentaram sinais clínicos de miopatia. Dentre esses animais, cinco apresentaram sinais subagudos leves a moderados e dois apresentaram sinais hiperagudos severos e decúbito lateral. Foram realizadas biópsias musculares utilizando a técnica percutânea, por agulha tipo Bergstrõm, no músculo glúteo médio em todos os animais acometidos. As amostras foram processadas por meio de técnicas histológicas (HE, Tricrômio de Gomori modificado) e histoquímicas (PAS, NADH, ATPase). Nos quadros clínicos mais leves, a principal alteração encontrada foi a presença de fibras vermelhas rajadas do tipo I e IIA, que estão associadas às alterações do metabolismo oxidativo e das funções mitocondriais, como ocorrem nas miopatias mitocondriais. Também foram observadas fibras atróficas do tipo I e IIA, além da presença de agregados subsarcolemais. Nos quadros mais severos o tecido muscular apresentou infiltrado inflamatório, aumento de colágeno, fagocitose, necrose, calcificação e regeneração muscular. Diante dos achados morfológicos, da resposta à terapia com vitamina E e Se e da baixa mortalidade quando comparado aos relatos de miopatia atípica, conclui-se que esse surto foi desencadeado por lesões mitocondriais, caracterizadas pelas fibras musculares vermelhas rajadas, possivelmente devido uma quebra da homeostase de vitamina E e Se, sendo compatível com o diagnóstico de miopatia nutricional.(AU)

Equine myopathies are classified according clinic, morphologic and molecular features in three groups: Non-exertional, exertional, and abnormal muscle membrane conduction. In spite the advances in diagnostic, the literature has reported outbreaks of equine myopathy without clear etiology in several countries. The aim of this study was to describe the histological and histochemical findings of muscle biopsies in an outbreak of equine myopathy. Seven 18 to 24-month-old Quarter horses showed clinical signs of myopathy. Five horses presented mild clinical signs and two horses had severe clinical signs with recumbency. Muscle biopsies were obtained from gluteal medium muscle by percutaneous technique with Bergstrom needle in all affected horses. Muscle samples were processed by histological (HE, modified gomori-trichrome) and histochemical (PAS, NADH, ATPase) technics. In animals with mild clinical signs, ragged red fibers type I and IIA, related to the oxidative metabolism dysfunction of mitochondria, was the main abnormality found. Muscle fiber atrophy and presence of subsarcolemmal aggregates in type I and IIA muscle fibers were also observed. More severe affected horses presented inflammatory infiltrate, proliferation of collagen, phagocytosis, necrosis and calcification. Based on the morphological findings, vitamin E therapy response associated with the low mortality when compared with atypical myopathy reports, We concluded that this outbreak was triggering for mitochondrial lesions, characterized by ragged red muscle fibers, probably due a breakdown homeostasis in vitamin E and Se, being compatible with nutritional myopathy diagnosis.(AU)

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