Orphanet Journal of Rare Diseases最新文献

{"title":"A real-world analysis of the impact of X-linked myotubular myopathy on caregivers in the United States.","authors":"Tina Duong, Tmirah Haselkorn, Beckley Miller, Julie Coats, Ivar Jensen, Erin Ward, Marie Wood, Robert J Graham, Laurent Servais","doi":"10.1186/s13023-025-03583-w","DOIUrl":"10.1186/s13023-025-03583-w","url":null,"abstract":"<p><strong>Background: </strong>X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy with multisystem involvement, which often includes the need for invasive ventilator support, gastrostomy tube feeding, and wheelchair use in approximately 80% of patients. The direct and indirect financial impact of extensive supportive care, as reported by caregivers of individuals with XLMTM, and the health-related quality of life (HRQoL) of caregivers has not been previously described. Here, we use a survey co-designed by patient advocates to provide objective information on the physical and financial challenges of caregiving for individuals with XLMTM.</p><p><strong>Methods: </strong>A real-world web-based survey was conducted in the United States between November 19, 2019, and January 23, 2020. The survey was developed in association with patient advocacy leaders from the XLMTM community, who were also caregivers of individuals with XLMTM. The survey included the EuroQol 5-dimension 5-level HRQoL instrument and visual analog scale, and a cost (direct and indirect medical costs) and healthcare resource questionnaire. The survey was shared among the XLMTM community by patient advocacy organizations. Caregivers who completed the survey and met the eligibility criteria were included. Descriptive statistics were conducted using Microsoft Excel.</p><p><strong>Results: </strong>Twenty-two caregiver respondents agreed to participate. All respondents completed the cost and health resource survey. Productivity loss varied between participants over the prior 12 months. Durable medical equipment expenses comprised most of the direct medical out-of-pocket costs. Non-medical expenditures (e.g. home and vehicle modifications) were higher than direct medical out-of-pocket costs. Twelve of the 22 respondents completed the HRQoL survey. The HRQoL domains most impacted were usual activities, anxiety/depression, and pain/discomfort.</p><p><strong>Conclusions: </strong>Findings from this real-world survey of caregivers for individuals with XLMTM describe the caregiver experience, as well as the multifaceted impact of the disease on caregiver productivity loss, out-of-pocket expenses, and HRQoL. XLMTM comes with financial constraints and substantial impacts on caregivers' physical and mental health. Understanding these gaps is crucial to support the caregivers who provide care for this medically fragile population.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"224"},"PeriodicalIF":3.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of patients with posterior urethral valves \"from the fetus to adolescence\": French national diagnostic and care protocol (NDCP).","authors":"Alaa El-Ghoneimi, Luke Harper, Ugo Maria Pierucci, Thomas Blanc, Jonathan Rosenblatt, Nicolas Sananes, Sophie Dreux, Marianne Alison, Fred Avni, Stéphane Decremer, Veronique Baudouin, Sayaka Oguchi, Dan Baruch, Pascale Rolland-Santan, Hedyeh Nadafi-Stoeffel, Cécile Bonnet, Annabel Paye-Jaouen, Eliane Raffet, Lise Natio, Berengere Desprez, Delphine Demede, Marc David Leclair, Matthieu Peycelon","doi":"10.1186/s13023-025-03712-5","DOIUrl":"10.1186/s13023-025-03712-5","url":null,"abstract":"<p><p>Posterior urethral valves (PUV) are congenital anomalies characterized by the persistence of mucosal folds in the urethra, leading to various degrees of obstruction. They are the most common cause of lower urinary tract obstruction in fetuses and children, with a severe prognosis, as one-third of affected children develop end-stage renal disease before adulthood. The French National Diagnostic and Care Protocol (NDCP) aim to provide healthcare professionals with guidelines for the optimal diagnostic and therapeutic management of PUV from the fetal stage to adolescence. The guidelines emphasize early diagnosis through prenatal ultrasound and the importance of a multidisciplinary approach involving pediatric urologists, nephrologists, and other specialists. It outlines prenatal interventions such as vesico-amniotic shunting and postnatal surgical options like endoscopic valve ablation to alleviate obstruction and preserve renal function. Long-term follow-up is crucial for monitoring renal function, managing bladder dysfunction, and preventing complications such as urinary tract infections and chronic kidney disease. The guidelines also identify off-label pharmaceuticals and necessary specialty products not typically covered by insurance. By standardizing care pathways and promoting consistent, high-quality care, the guidelines aim to improve the prognosis and quality of life for children with PUV, setting a benchmark for managing this rare condition in pediatric urology.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"225"},"PeriodicalIF":3.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cost of the diagnostic odyssey of patients with suspected rare diseases.","authors":"Rick Glaubitz, Luise Heinrich, Falko Tesch, Martin Seifert, Katrin Christiane Reber, Ursula Marschall, Jochen Schmitt, Gabriele Müller","doi":"10.1186/s13023-025-03751-y","DOIUrl":"https://doi.org/10.1186/s13023-025-03751-y","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with rare diseases often undergo a long diagnostic odyssey. However, there is little empirical evidence on the cost incurred during the diagnostic pathway for patients with suspected rare diseases. This study provides a comprehensive analysis of healthcare costs and utilization during the diagnostic pathway for a heterogeneous sample of patients with suspected rare diseases but unclear diagnosis.</p><p><strong>Methods: </strong>Using claims data from five German statutory health insurance organizations for the years 2014-2019, we analyzed costs and healthcare utilization of 1,243 patients (aged 0 to 82 years) with suspected rare diseases referred to a rare disease center. A control cohort was assigned using 1:75 exact matching on age, sex and place of residence.</p><p><strong>Results: </strong>In the years prior to referral to an expert center, healthcare utilization of patients with suspected rare diseases was, on average, substantially and significantly higher compared to a matched control cohort during the same observation period - e.g. in terms of the number of hospitalizations (3.1 (95%CI: 2.9-3.4) vs. 0.5 (95%CI: 0.5-0.5)), different diagnoses (50.0 (95%CI: 48.1-51.9) vs. 26.4 (95%CI: 26.2-26.5)), different active substances prescribed (12.7 (95%CI: 12.2-13.3) vs. 8.2 (95%CI: 8.2-8.3)) and the number of genetic tests (14.7 (95%CI: 12.6-16.7) vs. 0.3 (95%CI: 0.3-0.3)). We found evidence of heterogeneity in utilization by age and sex. On average, direct costs (inpatient, outpatient and prescription drug costs) of patients with suspected rare diseases during the diagnostic pathway were 7.6-fold higher than the costs of matched controls (€26,999 (95%CI: €23,751 - 30,247) vs. €3,561 (95% CI: € 3,455-3,667)). Inpatient costs were the main cost component, accounting for 62.5% of total costs.</p><p><strong>Conclusions: </strong>The diagnostic odyssey of patients with suspected rare diseases is associated with extensive healthcare utilization and high cost. Against this background, new ways to shorten the diagnostic journey have a high potential to decrease the financial burden related to rare diseases.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"222"},"PeriodicalIF":3.4,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The most bothersome symptoms in neuromuscular diseases: the ERN EURO NMD Survey.","authors":"Michelangelo Mancuso, Alessandro Colitta, Manuela Lavorato, Peter Van den Bergh, Janbernd Kirschner, Cornelia Kornblum, Lorenzo Maggi, Francois Lamy, Hanns Lochmüller, Marianne Nordstrøm, Edoardo Malfatti, Alessandra Ferlini, Davide Pareyson, Vincenzo Silani, Kleopas A Kleopa, Marianne de Visser, Antonio Atalaia, Teresinha Evangelista","doi":"10.1186/s13023-025-03742-z","DOIUrl":"https://doi.org/10.1186/s13023-025-03742-z","url":null,"abstract":"<p><strong>Background: </strong>Neuromuscular diseases (NMDs) comprise a range of genetic and acquired rare disorders that affect motor neurons, peripheral nerves, neuromuscular junctions and skeletal muscles, leading to significant impairments such as muscle weakness and fatigue resulting in functional limitations. This study aims to investigate the prevalence and severity of disease-related symptoms in adult patients with NMDs registered in the European Reference Network (ERN) EURO-NMD. A cross-sectional electronic survey was conducted with 1,253 participants who reported the severity of 28 symptoms, which were scored using multi-criteria decision analysis (MCDA).</p><p><strong>Results: </strong>The results identified muscle fatigue, weakness and impaired physical function/activity as the most severe and prevalent symptoms in all NMD groups, followed by coordination and/or balance problems, muscle stiffness, mental fatigue, and pain. Notably, the analysis highlighted differences in symptom severity between disease subtypes and underlined the need for standardised patient-reported outcome measures (PROMs) to address the broad heterogeneity of NMDs.</p><p><strong>Conclusions: </strong>The findings stress the critical importance of capturing patient perspectives to guide clinical care, research priorities and therapeutic development. This work argues for the development of uniform PROMs to better assess disease impact, natural history and treatment efficacy, contributing to improved patient-centred care across diverse NMD populations.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"221"},"PeriodicalIF":3.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prevalence of spontaneous pneumothorax in patients with BHD syndrome: a systematic review and meta-analysis.","authors":"Yanan Zhang, Yuling Wang, Jinxia Wang, Ping Li, Ruonan Lv, Juan Chen","doi":"10.1186/s13023-025-03726-z","DOIUrl":"https://doi.org/10.1186/s13023-025-03726-z","url":null,"abstract":"<p><strong>Background: </strong>Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of pneumothorax. This study aimed to determine the prevalence of spontaneous pneumothorax among individuals diagnosed with BHD syndrome.</p><p><strong>Method: </strong>A comprehensive literature search was conducted across PubMed, EMBASE, Cochrane Controlled Register of Trials (CENTRAL), and Web of Science databases up to March 10, 2024. Studies reporting on the prevalence of spontaneous pneumothorax in BHD syndrome patients were included. Eligibility assessment, data extraction, and quality assessment were performed independently by two reviewers. Random-effects or fixed-effect models were conducted to calculate pooled incidence rates, and subgroup analyses were performed to explore sources of heterogeneity. The publication bias was assessed by funnel plot and Egger's test.</p><p><strong>Results: </strong>Eighteen studies, conducted between 2009 and 2023, were included in the systematic review. The meta-analysis revealed a pooled incidence rate of spontaneous pneumothorax in BHD syndrome patients at 0.61 (95% CI 0.46; 0.76). Subgroup analyses based on region, study design, and diagnostic methods further elucidated variations in incidence rates among different patient groups. Specifically, the Asian subgroup demonstrated a higher pooled incidence rate of 0.71 (95% CI 0.60; 0.81), while the Caucasian subgroup showed a lower pooled incidence rate of 0.43 (95% CI 0.26; 0.60). The subgroup analysis by study design revealed a pooled incidence rate of 0.60 (95% CI 0.45; 0.76) for retrospective studies and 0.70 (95% CI 0.42; 0.98) for the sole prospective study. Additionally, the subgroup analysis by diagnostic methods showed pooled incidence rates of 0.64 (95% CI 0.48; 0.81) for studies using FLCN mutation testing and 0.51 (95% CI 0.33; 0.70) for those using clinical criteria and imaging findings. Potential publication bias was identified by Egger's test (P < 0.05).</p><p><strong>Conclusion: </strong>The study indicated a pooled prevalence rate of 61% for pneumothorax in BHD syndrome patients, with subgroup analyses revealing higher rates among Asian individuals and in prospective studies. Further researches, particularly large-sample prospective studies, are needed to address publication bias and improve the reliability of prevalence estimates.</p><p><strong>Prospero: </strong>CRD42024567520.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"218"},"PeriodicalIF":3.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of mobility, pain/discomfort, self-care, and mental health in patients with alpha-mannosidosis: an international caregiver and patient survey.","authors":"Karolina M Stepien, Sophie Thomas, Julia B Hennermann, Christina Lampe, Nicole M Muschol, Maria Juliana Ballesta-Martínez, Jordi Cruz, Mónica López-Rodríguez, Anneliese Barth, Martin Magner, Allan M Lund, Vasilica Plaiasu, Andrea Ballabeni, Francesca Donà, Heather M Morgan, Nathalie Guffon","doi":"10.1186/s13023-025-03694-4","DOIUrl":"https://doi.org/10.1186/s13023-025-03694-4","url":null,"abstract":"<p><strong>Background: </strong>Alpha-mannosidosis is a rare recessive lysosomal storage disorder with progressive multi-systemic impacts. In the absence of standardized monitoring protocols, there is insufficient understanding of disease progression over time. This study explored the evolution of the burden of illness and quality of life (QoL) experienced by patients with alpha-mannosidosis via an international patient and caregiver-based survey. The online survey was distributed to adult patients/caregivers of patients ≥ 10 years old. It included visual analogue scales (VAS; timepoints 5 years ago and now), multiple choice, and open text questions. We report a subset of functional and QoL data: walking ability, pain/discomfort, ability to self-care, and mental health.</p><p><strong>Results: </strong>Analyses include 51 responses from 18 countries: 26 patients were on velmanase alfa enzyme replacement therapy (ERT), seven had been treated with hematopoietic stem cell transplantation (HSCT) and 18 were untreated patients (UP). Over 5 years, VAS scores showed the least decline in walking ability for HSCT patients (+ 0.1 ± 1.9) compared to patients receiving ERT (+ 0.7 ± 1.2) and UP (+ 1.8 ± 2.0). A trend towards improvement in pain was only observed for those on ERT (-0.2 ± 2.0), both for pediatric and adult patients. Ability to self-care improved for patients treated with HSCT (-1.0 ± 1.8) and slightly improved with ERT (-0.3 ± 1.5) but worsened for UP (+ 0.6 ± 0.9). Similarly, a trend towards improvement in mental health scores was observed for patients on ERT (-0.4 ± 2.2).</p><p><strong>Conclusions: </strong>Alpha-mannosidosis is associated with a substantial and progressive burden in UP, including deterioration in walking ability, pain, self-care and mental health. The survey results suggest that treatment with ERT or HSCT may slow this natural progression of alpha-mannosidosis, with these patients following a different disease trajectory to those solely receiving supportive care. This study could inform the natural pathway of alpha-mannosidosis to recognize patients' needs, courses of care, and the design of interventional studies.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"217"},"PeriodicalIF":3.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leber hereditary optic neuropathy: utilities and carer burden from British and Irish participants.","authors":"Claire Lawrence, Emma Williams, Andrew Mumford, Steve Bojakowski, Julio Benedicto, Andrew Lloyd","doi":"10.1186/s13023-025-03737-w","DOIUrl":"https://doi.org/10.1186/s13023-025-03737-w","url":null,"abstract":"<p><strong>Background: </strong>Leber hereditary optic neuropathy (LHON) is a rare, maternally inherited, mitochondrial disease resulting in sudden, progressive central vision loss. The condition affects numerous aspects of daily life, functioning and overall health-related quality of life (HRQL), which may spillover to carers.</p><p><strong>Methods: </strong>Two studies were designed to estimate patient utilities associated with varying visual acuity in LHON (study 1) and to explore carer burden (study 2). In study 1, eight LHON health state vignettes (mild vision loss [LogMAR < 0.3] through to light perception [LogMAR ≥ 4]) were valued by the UK and Republic of Ireland (ROI) general pubic using the Health Utilities Index- 3 (HUI-3) and EQ-5D in an online survey (N = 360) and in time trade-off interviews (TTO; n = 120). In study 2, nine carers completed in-depth interviews exploring carer burden, the Care-related Quality of Life instrument (CarerQol), EQ-5D-5L and the Work Productivity and Activity Impairment Questionnaire (WPAI).</p><p><strong>Results: </strong>Study 1 demonstrated lower utilities for people with worse visual function. Mild vision loss (LogMAR < 0.3) was rated as 0.84 (HUI-3), 0.79 (EQ-5D) and 0.88 (TTO). Light perception (LogMAR ≥ 4), the most severe health state, was rated as 0.18 (HUI-3), 0.34 (EQ-5D), and 0.36 (TTO). In study 2, qualitative findings revealed substantial burden for many carers and family members. The most prominent impacts were emotional (e.g., guilt, devastation), especially related to the maternal inheritance of LHON. Impacts to carers' daily life, social life and relationships, work, and finances were also described. Standardised measures identified little impact on HRQL (EQ-5D-5L = 0.89), but some carer related burden (CarerQol-7D = 78.4). The WPAI revealed an overall work impairment of 15% and activity impairment of 37%.</p><p><strong>Conclusions: </strong>Findings suggest the HUI-3 may be more sensitive to the HRQL impact of vision loss compared to the EQ-5D and TTO method. The data indicate the potential value of an effective treatment for LHON. Qualitative findings describe the impact of LHON on carers. However, the burden described in the qualitative data was incongruent with quantitative measures, particularly the EQ-5D-5L. This demonstrates the value of conducting mixed-methods research and the importance of selecting measures which capture population-relevant concepts.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"219"},"PeriodicalIF":3.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic impact of whole exome sequencing in neurometabolic disorders in Syrian children: a single center experience.","authors":"Rawan Al Khudari, Sameer Baqla, Diana Al Asmar","doi":"10.1186/s13023-025-03732-1","DOIUrl":"https://doi.org/10.1186/s13023-025-03732-1","url":null,"abstract":"<p><strong>Background: </strong>Childhood neurometabolic disorders encompass a range of heterogeneous conditions often presenting with atypical or overlapping symptoms, making accurate diagnosis challenging, time-consuming, and costly. Whole exome sequencing (WES) has recently become a valuable diagnostic tool for suspected genetic or idiopathic neurometabolic disorders. This study evaluates the diagnostic utility of WES in Syrian patients with neurological and metabolic disorders, marking the first report of WES outcomes in this context.</p><p><strong>Results: </strong>Among 54 patients, 42 (78%) were from consanguineous families, of whom 38 (90%) had positive WES results. WES identified pathogenic or likely pathogenic variants in 28 patients (52%) and discovered 14 novel mutations. Seventeen patients (31%) had variants of uncertain significance (VUS) aligning with their clinical presentation, and nine (17%) had negative results. WES provided clinically relevant information for 45 patients (83%), with a definitive diagnosis in 28 (52%). Additionally, WES led to diagnostic changes in 45 cases (83%) and treatment alterations in 40 cases (74%).</p><p><strong>Conclusion: </strong>Our findings demonstrate the high diagnostic yield of WES and its substantial impact on clinical outcomes. WES has facilitated changes in diagnosis, treatment adjustments, prognostic modifications, and preventive measures, supporting its utility in undiagnosed neurometabolic diseases. This study advocates for WES in pediatric neurometabolic cases, particularly where consanguinity is present.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"220"},"PeriodicalIF":3.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reporting preclinical gene therapy studies in the field of Niemann-Pick type C disease according to the ARRIVE guidelines.","authors":"Charlotte Laurfelt Munch Rasmussen, Annette Burkhart, Torben Moos, Louiza Bohn Thomsen","doi":"10.1186/s13023-024-03479-1","DOIUrl":"https://doi.org/10.1186/s13023-024-03479-1","url":null,"abstract":"<p><p>The lack of essential information when reporting animal studies causing lower reproducibility has been stressed for decades. The ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines were first published in 2010, to improve reporting of animal research, making in vivo studies more transparent thereby improving the scientific quality. Regardless of an endorsement from the scientific community, there is still a continuous need to improve animal research reporting, which unfortunately also is the case in the field of Niemann-Pick type C disease (NPC). NPC is a lipid storage disorder, caused by mutations in either the Npc1 or Npc2 gene. Despite years of research, no cure for this fatal disease exists. In 2020, an updated version of the ARRIVE guidelines (ARRIVE 2.0), was published, describing the ten most essential elements to be included when reporting pre-clinical studies. Here we systematically reviewed the compliance with the ARRIVE guidelines using the \"ARRIVE Essential 10\" checklist in a series of pre-clinical studies investigating gene therapy as a treatment strategy for NPC. None of the reviewed papers fulfilled the ARRIVE 2.0 guidelines. Information regarding sample size, randomization, blinding, and statistical methodology was lacking. Hopefully, the newly updated ARRIVE guidelines will aid researchers in planning and publishing in vivo experiments in the future. More awareness of the importance of including these essential items is needed, both from editors, reviewers and researchers, for complete endorsement of the ARRIVE guidelines in the scientific community.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"214"},"PeriodicalIF":3.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postmarketing adverse events associated with onasemnogene abeparvovec: a real-world pharmacovigilance study.","authors":"Tianyu Chen, Qiying Chen, Jingfang Ye, Yuzhu Wu, Ting Liu, Yuezhen Zhang","doi":"10.1186/s13023-025-03715-2","DOIUrl":"https://doi.org/10.1186/s13023-025-03715-2","url":null,"abstract":"<p><strong>Background: </strong>Onasemnogene abeparvovec (OA) is an adeno-associated virus vector-based gene therapy indicated for the treatment of paediatric patients with spinal muscular atrophy(SMA) with biallelic mutations in the survival motor neuron 1 (SMN1) gene. This study focused on analysis of the postmarketing adverse events(AEs) of onasemnogene abeparvovec (OA) reported in the US Food and Drug Administration public data open project (openFDA) database to assess the safety of OA in the real world and to provide a reference for the rational use of this drug in the clinic.</p><p><strong>Results: </strong>In total, 1,959 AEs were reported with \"onasemnogene abeparvovec\" as the primary suspected drug. The top 5 most frequent AEs were pyrexia (461 cases), vomiting (434 cases), aspartate aminotransferase increase (284 cases), alanine aminotransferase increase (260 cases), and hepatic enzyme increase (237 cases). A total of 77 alert signals were generated, 60 of which were not included in the drug label. The top 5 signals included troponin I increase ( ROR of 895.21, 95% CI: 734.43-1091.18), troponin T increase ( ROR of 313.30, 95% CI:220.85-444.44), rhinovirus infection ( ROR of 175.80, 95% CI:130.86-236.17), troponin increase ( ROR of 143.49, 95% CI:114.96-179.10), and increased bronchial secretion ( ROR of 142.71, 95% CI:96.63-210.77). Further analysis of AEs associated with gender and age differences identified 14 high-risk signals related to gender and 10 high-risk signals related to age. Female patients should be vigilant for vomiting, thrombotic microangiopathy, increased troponin T, proteinuria, haematuria, haemolytic anaemia, urinary tract infection, generalised oedema, and atypical haemolytic uraemic syndrome. Male patients should be alert to increased hepatic enzyme, increased bronchial secretion, respiratory tract infection, pallor, and increased blood creatine phosphokinase MB. Patients under 2 years of age should be vigilant for lethargy, increased monocyte count, decreased blood creatinine, and decreased neutrophil count. Patients over 2 years of age should be alert to hypertension, haematuria, rhinovirus infection, increased blood creatine phosphokinase, headache, and malaise.</p><p><strong>Conclusions: </strong>Mining of OA alert signals using the openFDA database provides supplementary information on AEs not included in the drug label. Clinical attention should be focused on common, strong-signal, and label-unmentioned AEs to optimise medication regimens and control risks in clinical use.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"215"},"PeriodicalIF":3.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}