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Background Pompe disease is caused by pathogenic variants in the GAA gene, resulting in lysosomal acid α-glucosidase (GAA) deficiency. The prevalence of Pompe disease is not well-defined, and estimates vary by geographic region. We evaluated the global epidemiology of Pompe disease and the potential reasons for differing prevalence estimates using published data from worldwide newborn screening (NBS) programs and population-based studies. Methods A comprehensive literature search in PubMed was conducted in July 2023, updated in March 2024, and validated with an Embase search in June 2024. Search terms included Pompe disease, GSDII, prevalence, incidence, epidemiology, survival, mortality, and NBS. Studies were included based on robust epidemiological methods, the presence of disease definition, and publication within the past 5 years. We identified 1210 abstracts, of which 295 met recency criteria, 30 were deemed relevant, and 11 met all inclusion criteria. Results Prevalence estimates and GAA enzyme activity cutoff values varied across geographic regions. In NBS studies, the birth prevalence of infantile-onset Pompe disease (IOPD) ranged from 1 in 297,387 in Japan to 1 in 62,186 in Taiwan, and late-onset Pompe disease (LOPD) ranged from 1 in 82,914 in Taiwan to 1 in 17,133 in Pennsylvania. Data from the French National Pompe Registry (N = 246) showed an increase in diagnosis of LOPD from 2.6/year before 2001 to 10.6/year during 2001–2010 and 12.8/year during 2011–2015. Enzyme cutoffs in dried blood spots varied from < 3% of lymphocyte mean to 2.10 μmol/L/h to ≤ 18% of the daily median. Three studies noted higher prevalence in populations of African descent, and two noted a higher frequency of pseudodeficiency alleles in Asian populations. Conclusions This scoping review confirmed that prevalence estimates differ for IOPD and LOPD and vary by geographic region, potentially by race and ethnicity. It highlights the need to standardize screening and diagnosis methods, genetic testing protocols, and uniform disease classification between IOPD and LOPD.

Skeletal muscle is a heterogenous tissue comprised primarily of myofibers, commonly classified into three fiber types in humans: one “slow” (type 1) and two “fast” (type 2A and type 2X). However, heterogeneity between and within traditional fiber types remains underexplored. We applied transcriptomic and proteomic workflows to 1050 and 1038 single myofibers from human vastus lateralis , respectively. Proteomics was conducted in males, while transcriptomics included ten males and two females. We identify metabolic, ribosomal, and cell junction proteins, in addition to myosin heavy chain isoforms, as sources of multi-dimensional variation between myofibers. Furthermore, whilst slow and fast fiber clusters are identified, our data suggests that type 2X fibers are not phenotypically distinct to other fast fibers. Moreover, myosin heavy chain-based classifications do not adequately describe the phenotype of myofibers in nemaline myopathy. Overall, our data indicates that myofiber heterogeneity is multi-dimensional with sources of variation beyond myosin heavy chain isoforms. Moreno-Justicia and colleagues report transcriptomic and proteomic pipelines to explore heterogeneity within human skeletal muscle fibers, identifying sources of fiber heterogeneity in healthy individuals and children with nemaline myopathy.

Human T-cell leukemia virus type 1 (HTLV-1) causes inflammatory diseases and is associated with various muscle abnormalities, including polymyositis. Elevated serum creatine kinase (CPK) levels are typically indicative of muscle damage. This study aimed to determine the prevalence of HTLV-1 associated inflammatory myopathies (HAIM) in a large cohort of People living with HTLV-1 from Salvador, Brazil. Additionally, we sought to describe the clinical, laboratory, and histopathological findings of seven HTLV-1-infected patients with persistent hyperCKemia. This study included 503 HTLV-1-infected patients from a cohort in Salvador, Brazil, who were analyzed for creatine phosphokinase (CPK) levels. Clinical, laboratory, and pathologic examinations were performed in patients whose CPK levels were above the upper limit of the normal range in the two tests performed at different time points. Polymyositis was the main cause of HAIM in the study population, with a prevalence rate of 0.6%. Two cases were diagnosed with muscular dystrophy and mitochondrial disease, and in two other patients the cause of hyperCKemia could not be determined and is currently under investigation. Polymyositis was the main cause of HAIM in this cfohort of People living with HTLV-1.

Somatic neurological complications are an underexplored component of post-acute sequelae of SARS-CoV-2 infection. We evaluated long-term somatic neurological symptoms, examination findings, and suspected diagnoses among adults hospitalized for COVID-19. A total of 708 survivors were assessed 6–11 months after discharge using a structured three-step neurological evaluation based on the World Health Organization Protocol for Epidemiologic Studies of Neurologic Disorders : an adapted symptom questionnaire, a brief standardized neurological examination, and a full neurological consult. Muscle weakness, gait impairment, and paresthesias remained the most frequent symptoms at follow-up. Longer hospital stay predicted all three symptoms, and diabetes was associated with both gait impairment and paresthesias. Common examination findings included monoparesis, hemiparesis, and gradient-pattern sensory loss. Clinically suspected diagnoses included neuromuscular disease in 26%, cerebrovascular disease in 10%, and epilepsy in only 2.7% of cases. Logistic regression linked neuromuscular disease to paresthesias and tandem-walk failure, cerebrovascular disease to facial paralysis, and epilepsy to loss-of-contact episodes. A simplified screening model derived through best-subsets selection identified five informative items from the WHO protocol: paresthesias, facial paralysis, tandem walk, index–nose test, and loss-of-contact episodes. These findings indicate that somatic neurological abnormalities remain frequent months after severe COVID-19 and that a brief bedside subset may support efficient post-COVID neurological triage.

Early diagnosis of genetic rare diseases is an unmet need in Brazil, where an estimated 10–13 million people live with these conditions. Increased use of chromosome microarray assays, exome sequencing, and whole genome sequencing as first-tier testing techniques in suitable indications can shorten the diagnostic odyssey, eliminate unnecessary tests, procedures, and treatments, and lower healthcare expenditures. A selected panel of Brazilian experts in fields related to rare diseases was provided with a series of relevant questions to address before a multi-day conference. Within this conference, each narrative was discussed and edited through numerous rounds of discussion until agreement was achieved. The widespread adoption of exome sequencing and whole genome sequencing in Brazil is limited by various factors: cost and lack of funding, reimbursement, awareness and education, specialist shortages, and policy issues. To reduce the burden of rare diseases and increase early diagnosis, the Brazilian healthcare authorities/government must address the barriers to equitable access to early diagnostic methods for these conditions. Recommendations are provided, including broadening approved testing indications, increasing awareness and education efforts, increasing specialist training opportunities, and ensuring sufficient funding for genetic testing.

Introduction and hypothesisThe aim was to analyze the long-term effects of muscle-derived stem cells (MDSCs) therapy in traumatized urethras of female rats regarding messenger ribonucleic acid (mRNA) expression of collagens 1 and 3, Ngf and Ki67; and the mRNA and protein expression of Myh11 and Myh2.MethodsMuscle-derived stem cells were injected into the tail vein of rats 3 days after trauma by vaginal distention. Urethras were analyzed from 30 animals divided into three groups: control without injury or treatment, trauma (30 days post-injury), and MDSC (30 days post-injury who received MDSC therapy). Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed. The Kruskal–Wallis and ANOVA tests were used with p < 0.05 indicating significance.ResultsWe detected increased Myh11 and Myh2 mRNA expression in the trauma group compared with the control group (p = 0.03 and p = 0.04 respectively). Ki67 and Col1a1 genes were overexpressed in the MDSC group compared with both the trauma (p = 0.02 and p = 0.008 respectively) and the control group (p = 0.01 and p = 0.03 respectively). Col3a1 gene was upregulated in the MDSC compared with the control group (p = 0.03). Ngf mRNA level was lower in the MDSC group than in the trauma group (p = 0.002). Myh11, Myh2, and Desmin proteins were overexpressed in the MDSC compared with the trauma group (1.5-fold, p = 0.01; 1.5-fold, p = 0.04; 1.3-fold, p = 0.01 respectively).ConclusionsMuscle-derived stem cell therapy may have had long-term structural and molecular effects on the injured urethra of female rats, particularly on markers of cell proliferation, neural growth factor, extracellular matrix, and muscle content. This study suggests that MDSC therapy acted mainly to produce urethral sphincter regeneration marked by increased immunohistochemical expression of the proteins desmin, smooth muscle Myh11, and skeletal muscle Myh2.

Nemaline myopathy (NM) is one of the most common non-dystrophic genetic muscle disorders. NM is often associated with mutations in the NEB gene. Even though the exact NEB -NM pathophysiological mechanisms remain unclear, histological analyses of patients’ muscle biopsies often reveal unexplained accumulation of glycogen and abnormally shaped mitochondria. Hence, the aim of the present study was to define the exact molecular and cellular cascade of events that would lead to potential changes in muscle energetics in NEB -NM. For that, we applied a wide range of biophysical and cell biology assays on skeletal muscle fibres from NM patients as well as untargeted proteomics analyses on isolated myofibres from a muscle-specific nebulin‐deficient mouse model. Unexpectedly, we found that the myosin stabilizing conformational state, known as super-relaxed state, was significantly impaired, inducing an increase in the energy (ATP) consumption of resting muscle fibres from NEB -NM patients when compared with controls or with other forms of genetic/rare, acquired NM. This destabilization of the myosin super-relaxed state had dynamic consequences as we observed a remodeling of the metabolic proteome in muscle fibres from nebulin‐deficient mice. Altogether, our findings explain some of the hitherto obscure hallmarks of NM, including the appearance of abnormal energy proteins and suggest potential beneficial effects of drugs targeting myosin activity/conformations for NEB -NM.

Sporadic inclusion body myositis (sIBM) is considered the most common acquired myopathy aged over 50 years. The disease is characterized by a particular process of muscle degeneration characterized by abnormal deposit of protein aggregates in association with inflammation. The aim of this study was to present clinical and muscle histopathological findings, including immunostaining for LC3B, p62, α-synuclein, and TDP-43, in 18 patients with sIBM. The disease predominated in males (61%) and European descendants, with onset of clinical manifestations around 59 years old. The most common symptoms were muscle weakness, falls, dysphagia, and weight loss. Hypertension was the main comorbidity. Most of the cases presented with paresis predominantly proximal in lower limbs and distal in upper limbs. Immunosuppressive treatment showed to be not effective. Muscle histological findings included dystrophic changes, endomysial inflammation, increased lysosomal activity, and presence of rimmed vacuoles and of beta-amyloid accumulation, in addition to high frequency of mitochondrial changes. There was increased expression of LC3B, p62, α-synuclein, and TDP-43 in muscle biopsies. The sIBM has characteristic clinical and histological findings, and the use of degeneration and autophagic markers can be useful for the diagnosis.

Glucocorticoids represent some of the most prescribed drugs that are widely used in the treatment of neuromuscular diseases, but their usage leads to side effects such as muscle atrophy. However, different synthetic glucocorticoids can lead to different muscle effects, depending upon its chemical formulation. Here, we intended to demonstrate the muscle histologic and molecular effects of administering different glucocorticoids in equivalency and different dosages. Methods: Seventy male Wistar rats distributed into seven groups received different glucocorticoids in equivalency for ten days or saline solution. The study groups were: Control group (CT) saline solution; dexamethasone (DX) 1.25 or 2.5 mg/kg/day; methylprednisolone (MP) 6.7 or 13.3mg/kg/day; and deflazacort (DC) 10 or 20 mg/kg/day. At the end of the study, the animals were euthanized, and the tibialis anterior and gastrocnemius muscles were collected for metachromatic ATPase (Cross-sectional area (CSA) measurement), Western blotting (protein expression of IGF-1 and Ras/Raf/MEK/ERK pathways) and RT-PCR (MYOSTATIN, MuRF-1, Atrogin-1, REDD-1, REDD-2, MYOD, MYOG and IRS1/2 genes expression) experiments. Results: Muscle atrophy occurred preferentially in type 2B fibers in all glucocorticoid treated groups. DC on 10 mg/kg/day was less harmful to type 2B fibers CSA than other doses and types of synthetic glucocorticoids. In type 1 fibers CSA, lower doses of DC and DX were more harmful than high doses. DX had a greater effect on the IGF-1 pathway than other glucocorticoids. MP more significantly affected P-ERK1/2 expression, muscle fiber switching (fast-to-slow), and expression of REDD1 and MyoD genes than other glucocorticoids. Compared to DX and MP, DC had less of an effect on the expression of atrogenes (MURF-1 and Atrogin-1) despite increased MYOSTATIN and decreased IRS-2 genes expression. Conclusions: Different glucocorticoids appears to cause muscle atrophy affecting secondarily different signaling mechanisms. MP is more likely to affect body/muscles mass, MEK/ERK pathway and fiber type transition, DX the IGF-1 pathway and IRS1/2 expression. DC had the smallest effect on muscle atrophic response possibly due a delayed timing on atrogenes response.