Journal of neuromuscular diseases最新文献

{"title":"Urinary N-terminal titin fragment ascertained as biomarker in a small cohort of limb-girdle muscular dystrophy LGMDR1-calpain 3 related.","authors":"Andrea Valls, Cristina Ruiz-Roldán, Jenita Immanuel, Pilar Camaño, Juan José Poza, Roberto Fernández-Torrón, Adolfo López de Munain, Amets Sáenz","doi":"10.1177/22143602251323629","DOIUrl":"10.1177/22143602251323629","url":null,"abstract":"<p><p>We aimed to investigate the validity of urinary N-terminal titin (TTN) fragment as a biomarker for limb-girdle muscular dystrophy LGMDR1-calpain 3 related. Thirteen LGMDR1 patients and eleven healthy controls were enrolled for the study. LGMDR1 patients had significantly increased urinary N-terminal titin fragment concentrations than age-matched controls. Even if urinary level of titin decreased with aging, it was still high in wheelchair bound patients. Thus, our findings indicate that urinary N-terminal titin fragment is a non-invasive measure of muscle damage in LGMDR1, which could be used in disease monitoring in clinical trials even in wheelchair-bound patients.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"683-688"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pilot study of canakinumab (Ilaris) in steroid naïve children with Duchenne muscular dystrophy demonstrates safety and exploratory changes in potential serum protein response biomarkers.","authors":"Christopher F Spurney, Jessica Chong, Heather Gordish-Dressman, Yetrib Hathout","doi":"10.1177/22143602251319177","DOIUrl":"10.1177/22143602251319177","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD) is a progressive muscular disease associated with muscle fiber degeneration and increased inflammatory responses including Interleukin-1 beta (IL-1β) and other cytokines. Canakinumab (Ilaris) is an anti-human IL-1β monoclonal antibody that neutralizes IL-1β.</p><p><strong>Methods: </strong>We completed an open-label, single dose pilot study of canakinumab 2 mg/kg subcutaneous injection in steroid naïve boys with DMD older than 2 years of age to determine safety and potential serum response biomarkers of efficacy at 4-weeks post treatment. Proteome profiling was performed using high throughput multiplexing aptamer SomaScan assay based technology targeting 1,500 unique serum proteins.</p><p><strong>Results: </strong>Three subjects completed the study with no adverse events reported and no significant changes in safety labs. Proteomic analysis within 4 weeks of treatment identified significantly decreased inflammation associated factors including plasma serine protease inhibitor, interleukin-6 receptor alpha, Lymphocyte antigen 86, Immunoglobulin D and myostatin. Significantly increased proteins included muscle-associated proteins aldolase A and lactate dehydrogenase B.</p><p><strong>Conclusions: </strong>Canakinumab 2 mg/kg dose is safe for children with DMD and demonstrated potential response biomarkers of efficacy in treating related muscle disease. Canakinumab did not affect the circulating levels of IL-1β but did decrease some key proinflammatory markers and myostatin. Increased muscle specific proteins could be associated with increased physical activities or damage seen in young patients with DMD. Further studies using canakinumab for a longer treatment period may demonstrate increased benefit.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"641-647"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient and caregiver spinal muscular atrophy treatment attribute preferences in Latin America.","authors":"Victoria Saenz, Marijana Chlistalla, Nayara Carlos, Claudia Castiglioni, Maria Soledad Monges, Laurent Servais, Edmar Zanoteli","doi":"10.1177/22143602251320267","DOIUrl":"10.1177/22143602251320267","url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease associated with a significant burden of illness to both patients and caregivers; however, there is little evidence available regarding how patients and caregivers evaluate potential treatment benefit-risk profiles. As access to SMA disease-modifying therapies increases, it is imperative to understand which treatment attributes drive treatment choices.</p><p><strong>Objective: </strong>To identify which treatment attributes drive treatment choices in adults with SMA and caregivers of children with SMA across nine countries in Latin America.</p><p><strong>Methods: </strong>A discrete choice experiment (DCE) survey was developed for market research using data collected via qualitative interviews and consultations with medical experts. Adults with Type 2/3 SMA and caregivers of children with Types 1-3 SMA were recruited by patient advisory groups and physician referrals. Respondents completed a 30-min, online survey that collected patient demographics, disease-specific information, and quality of life data (via the EQ-5D-5L), and included the DCE, in which respondents were asked to choose between 14 sets of hypothetical treatment profiles. Data were pooled for analysis, as the country-level sample sizes were small. Raw data were aggregated in Microsoft Excel. Statistical testing was performed using data tables and SPSS (as appropriate). Demographic data were summarized descriptively.</p><p><strong>Results: </strong>A total of 143 respondents (45 adults with SMA and 98 caregivers) completed the online survey. Most respondents were from Argentina (35.0%) or Brazil (19.6%). Breathing function outcome was the most important treatment attribute for caregivers, while adults with SMA placed greater importance on motor function outcome. Both adults with SMA and caregivers placed the greatest importance on improvements in function compared with worse or stable outcomes.</p><p><strong>Conclusions: </strong>Understanding treatment attribute preferences at a regional level will improve shared medical decision-making for individuals with SMA.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"648-661"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of the ENCALS predictive survival model in assessing the effect of the 24/44 inclusion criteria in FORTITUDE-ALS.","authors":"Tyrell Simkins Lead, Jeremy M Shefner, Stuart Kupfer, Fady I Malik, Lisa Meng, Stacy A Rudnicki, Jenny Wei, Ruben Pa van Eijk","doi":"10.1177/22143602251336058","DOIUrl":"10.1177/22143602251336058","url":null,"abstract":"<p><p>FORTITUDE-ALS was a study evaluating reldesemtiv in people living with ALS. Post-hoc analysis identified larger treatment effects in those with symptom onset ≤24 months and baseline ALSFRS-R ≤ 44 (24/44 criteria). Using the ENCALS risk score (RS), we analyzed how the 24/44 criteria changed the eligible population. Of the 272 participants meeting the 24/44 criteria, 73% had very short to intermediate RS compared to 18% not meeting the criteria. Though the 24/44 criteria enriched the FORTITUDE-ALS population with rapidly progressing patients, they did not completely exclude all patients with a very long predicted survival.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"679-682"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short- and long-term natural history of three neurodegenerative biomarkers among middle-aged and older adults.","authors":"Rikuta Hamaya, Pamela M Rist, Varant Kupelian, Anthony L Gotter, Jihee Sohn, Carrie E Rubel, J Michael Gaziano, JoAnn E Manson, Howard D Sesso","doi":"10.1177/22143602241301636","DOIUrl":"10.1177/22143602241301636","url":null,"abstract":"<p><strong>Background: </strong>Little is known about the longitudinal trajectories of novel neurodegenerative biomarkers including neurofilament light (NfL), tau, and glial fibrillary acidic protein (GFAP).</p><p><strong>Objectives: </strong>We aimed to investigate the short- and long-term natural history of these biomarkers measured longitudinally among healthy adults.</p><p><strong>Methods: </strong>In this cohort study from the Physicians' Health Study (PHS), VITamin D and OmegA-3 TriaL (VITAL), and COcoa Supplement and Multivitamin Outcomes Study (COSMOS), we included 1299 adults with bloods collected 2 years (VITAL and COSMOS) or 14 years (PHS) apart and without diagnosed neurodegenerative diseases before baseline or during follow-up through two years after the final blood collection. Associations between baseline characteristics and changes in NfL, tau, and GFAP were evaluated.</p><p><strong>Results: </strong>Mean (SD) age at baseline was 49.8 (6.8), 67.5 (6.2), and 70.3 (5.7) in PHS, VITAL, and COSMOS, respectively. PHS enrolled only men while ∼50% of the VITAL and COSMOS populations in this study were men. Median percent changes (IQR) of NfL were 40.6% (2.4, 58.2) increase over 14 years (PHS) and 8.5% (-6.6, 28.6) over 2 years (VITAL and COSMOS); increases in tau were 101% (10.7, 285) over 14 years and 11.8% (-35.2, 106) over 2 years; and increases in GFAP were 25.1% (-1.7, 23.8) over 14 years and 5.6% (-12.8, 28.6) over 2 years. In multivariable models, age was most strongly and robustly associated with 14-year changes in NfL and GFAP (adjusted p<0.001), and increases in levels accelerated at older ages. No baseline variables were associated with changes in tau.</p><p><strong>Conclusion: </strong>Increases in NfL and GFAP accelerated with age, highlighting the need to improve our understanding of the clinical relevance of short- and long-term changes in these neurodegenerative biomarkers in large-scale, long-term cohorts.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"670-678"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thinking outside the box: A re-evaluation of Canadian recommended outcome measures in adult spinal muscular atrophy - report of a national consensus workshop.","authors":"Colleen O'Connell, Xavier Rodrigue, Victoria Hodgkinson, Katie Henley, Jeremy Slayter, Alberto Aleman, Dorothy Drost, Aaron Izenberg, Beth Knowles, Hanns Lochmüller, Marianne Nury, Erin O'Ferrall, Homira Osman, Kerri Schellenberg, Christen Shoesmith, Christine Stables, Susi Vander Wyk, Grace Westbury","doi":"10.1177/22143602251336076","DOIUrl":"10.1177/22143602251336076","url":null,"abstract":"<p><p>BackgroundDisease-modifying therapies for persons with spinal muscular atrophy (SMA) has led to greater need and demand for relevant outcomes assessments. Such tools help monitor disease progression, assess treatment response, and inform clinical management. Canadian SMA clinicians participated in a Delphi process to achieve a 2021 national consensus on recommended outcomes, recognizing future reassessment would be essential given the evolving field and gaps in patient-reported and bulbar measures.ObjectiveDerive updated Canadian consensus of recommended outcome measures for adults with SMA.MethodsA national consensus workshop was held with SMA clinicians, patient/family representatives, research leaders, national registry and advocacy organizations. Clinics and registry experience and data were presented and discussed, utility of current and additional outcomes reviewed. Long and short lists of measures were generated, with voting to derive consensus.ResultsPractical implementation, value of data, and relevance to persons with SMA were key considerations. Consensus was achieved to 'think outside the box', recognizing a spectrum of function and need to choose the right outcome measure for the right patient at the right time. Measures with greater acceptance for adults were selected, and bulbar measures introduced. Eight outcome measures are recommended; 4 motor, 2 respiratory and 2 patient reported domains, with use based on the individuals level of function. The Revised Upper Limb Module was deemed to have broadest applicability except in the strongest and weakest adults. Additional measures are included as optional and exploratory.ConclusionsEmploying measures meaningful for clinicians, researchers, and persons living with SMA is essential to ensuring quality data collection and an engaged patient-centred clinical team. Clinicians should select measures based on the person's functional ability and goals. Building a national community of practice to support clinical and research practice, including standardized outcome measure training, will be a key next step in dissemination and advocacy.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"699-710"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prospective observational study assessing the functional disease progression of LGMDR4, betasarcoglycan-related limb girdle muscular dystrophy.","authors":"Megan A Iammarino, Natalie F Reash, Kiana Shannon, Maggie Dugan, Kelly Lehman, Alayne Meyers, Jerry R Mendell, Lindsay N Alfano, Linda P Lowes","doi":"10.1177/22143602251339219","DOIUrl":"10.1177/22143602251339219","url":null,"abstract":"<p><strong>Introduction: </strong>Limb-girdle muscular dystrophy (LGMD) R4, betasarcoglycanopathy, is a progressive muscle disease that frequently presents in childhood and results in loss of ambulation around 20 years of age. With interventional trials on the horizon it is essential to document functional disease progression using standardized performance outcome assessments (PerfO).</p><p><strong>Methods: </strong>We present a prospective longitudinal observational study of individuals recruited through both Nationwide Children's Hospital neuromuscular clinics and through outreach events held in an area with a high incidence of Founder variant (c.452C > G). PerfOs included the NorthStar Assessment for limb-girdle dystrophies (NSAD), Performance of Upper Limb (PUL), timed function tests, and spirometry, as appropriate.</p><p><strong>Results: </strong>Forty-six individuals enrolled (aged 3-55 years) with 22 (55%) ambulant. Most PerfOs quantified change over time. We found heterogeneity of functional abilities at all ages. In our cohort, children's performance improved until around age 7, followed by a plateau until around 10-12 years. The ability to rise from the floor was the first milestone lost and was unable to be completed by anyone who took longer than 7.7 s on the 10-meter. Further, performance on select PerfOs were related to skills of functional independence, informing clinical care and data driven trial design.</p><p><strong>Conclusion: </strong>There is a great deal of functional heterogeneity. The selected PerfOs measured motor function and disease progression in individuals with LGMDR4, for the benefit of both data driven clinical management and clinical trial design.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"630-640"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rehabilitation research in spinal muscular atrophy: a call to action.","authors":"Charlotte Lilien, Leslie Nelson, Lisa Edel, Danielle Forrest, Timothy Estilow, Katlyn E McGrattan, Tina Duong, Giorgia Coratti","doi":"10.1177/22143602251364945","DOIUrl":"https://doi.org/10.1177/22143602251364945","url":null,"abstract":"<p><p>DesignThe landscape of spinal muscular atrophy drastically changed following the introduction of disease-modifying therapies, emphasizing the need for comprehensive rehabilitation strategies to maximize functional outcomes. Our aim is to identify the barriers faced by healthcare professionals in conducting rehabilitation research for spinal muscular atrophy and suggest potential solutions to increase evidence-based care.MethodsWe performed a narrative review of rehabilitation intervention studies with a quality assessment focusing on the research characteristics of each study and an international survey questioning healthcare professionals on their major areas of difficulty in conducting interventional studies.ResultsThe review highlighted a predominantly low to unacceptable quality of the 36 retained studies across four healthcare professional domains responsible for rehabilitation: physiotherapy/physical therapy (18), occupational therapy (4), respiratory therapy (10), and speech and language therapy/speech language pathology (4).The survey was completed by 204 health care providers from 35 countries. Funding was found to be the most significant barrier to rehabilitation research, followed by study design and recruitment challenges.ConclusionOur findings highlight the urgent need for randomized controlled trials and standardized methodologies to develop robust, evidence-based multi-disciplinary rehabilitation strategies that better support individuals with spinal muscular atrophy in achieving optimal functional outcomes in the era of disease-modifying treatments.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251364945"},"PeriodicalIF":3.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bullying experiences of youth with neuromuscular disorders and their well-being: A survey study.","authors":"Christina Ippolito, Marc-Olivier Deguise, Hanns Lochmüller, Hugh J McMillan, Laura McAdam","doi":"10.1177/22143602251369279","DOIUrl":"https://doi.org/10.1177/22143602251369279","url":null,"abstract":"<p><strong>Purpose: </strong>Bullying is a widespread problem in Canada and throughout the world. Children and youth with chronic illnesses or physical disabilities are more likely to be targets of bullying of all kinds. However, there is a paucity of research about bullying involving youth with neuromuscular disorders. The study aimed to assess the prevalence of bullying in youth with neuromuscular disorders and how bullying rates impact their quality of life and well-being.</p><p><strong>Methods: </strong>An online survey was administered at a single timepoint to youth with a neuromuscular disorder. The survey captured data about demographics, bullying frequency, quality of life, and emotional well-being. Descriptive statistics summarized demographic and bullying data. Spearman rank correlations measured the relationships between bullying prevalence and quality of life/well-being.</p><p><strong>Results: </strong>Twenty-nine participants completed the survey (22 male; mean age = 13 years, 10.8 months (SD = 2 years, 10.8 months). Twenty-four of 29 participants (82.8%) had been bullied at some point in their life. Participants reported being bullied most frequently for their appearance and their disability. Bullying did not correlate with quality of life and well-being.</p><p><strong>Conclusions: </strong>Participants with neuromuscular disorders reported high rates of bullying without impacts on quality of life and well-being. We posit participants exhibit resilience.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251369279"},"PeriodicalIF":3.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of novel and recurrent <i>SPTLC2</i> variants in childhood-onset amyotrophic lateral sclerosis: Insights into sphingolipid dysregulation.","authors":"Xiaona Fu, Kenneth Gable, Sita D Gupta, KaiLi Zhang, Bingbing Jia, Wenjun Wang, Xinying Yang, Lu Wang, Lin Ge, Carsten G Bönnemann, Teresa M Dunn, Hui Xiong","doi":"10.1177/22143602251370586","DOIUrl":"https://doi.org/10.1177/22143602251370586","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder that progressively affects motor neurons. Gain-of-function mutations in serine palmitoyltransferase (SPT) genes, notably <i>SPTLC1</i> and <i>SPTLC2</i>, have been linked to juvenile ALS. Here, we describe two childhood-onset ALS cases with distinct SPTLC2 mutations, providing new insights into sphingolipid dysregulation and its role in ALS pathogenesis.</p><p><strong>Material and methods: </strong>Two Chinese patients with early-onset ALS, both carrying <i>SPTLC2</i> mutations, were recruited from Beijing Children's Hospital. We conducted whole-exome sequencing (WES) to identify genetic variants, followed by Sanger sequencing for validation. Sphingolipid profiles were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Clinical evaluations included neurological assessments, brain MRI and electromyography. Additionally, mutant cell lines were established to assess the functional effects of the specific mutations.</p><p><strong>Results: </strong>Patient 1, a 6-year-old male, exhibited a novel heterozygous de-novo <i>SPTLC2</i> variant (c.197T > G, p.T66R). Patient 2, a 7-year-old female, had a recurrent heterozygous de-novo SPTLC2 variant (c.778G > A, p.E260K). Both patients showed elevated levels of specific sphingolipids compared to controls, with distinct profiles between the <i>SPTLC2</i>-ALS and <i>SPTLC1</i>-hereditary sensory and autonomic neuropathy type 1 (HSAN1) cases. The novel p.T66R mutation was predicted to alter protein interactions within the SPT complex, potentially impairing sphingolipid homeostasis. Functional studies further revealed that the p.T66R variant reduces the inhibitory regulation of SPT by ORMDL proteins, leading to unrestrained SPT activity and excess sphingolipid production.</p><p><strong>Conclusions: </strong>Our findings identify a novel <i>SPTLC2</i> variant linked to childhood-onset ALS and reveal altered sphingolipid profiles associated with different genetic mutations. These results underscore the importance of sphingolipid metabolism in ALS and suggest potential avenues for targeted therapeutic interventions. Further research is needed to explore treatment options aimed at modulating sphingolipid levels and correcting genetic defects, as well as investigating potential biomarkers for early diagnosis.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251370586"},"PeriodicalIF":3.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}