Orphanet Journal of Rare Diseases最新文献

{"title":"Clinical and genetic landscape of neuronopathic gaucher disease in Ukraine: hepatosplenomegaly and diagnostic delay.","authors":"Nataliia Samonenko, Nataliia Olkhovych, Olena Okhotnikova, Nataliia Gorovenko","doi":"10.1186/s13023-026-04578-x","DOIUrl":"10.1186/s13023-026-04578-x","url":null,"abstract":"<p><strong>Background: </strong>Neuronopathic Gaucher disease (GD types II and III) represents rare and severe phenotypes of glucocerebrosidase deficiency, characterized by neurological involvement and variable systemic manifestations. Data on clinical presentation and genotype-phenotype patterns in Eastern European populations remain limited.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of 92 patients with confirmed Gaucher disease followed at the National Children's Specialized Hospital \"Okhmatdyt\" (Kyiv, Ukraine) between 2001 and 2024. Among them, 4 patients had type II and 6 had type III GD. Diagnosis was established by measurement of leukocyte β-glucocerebrosidase activity and molecular analysis of the GBA1 gene. Clinical, laboratory, and imaging data were analyzed descriptively.</p><p><strong>Results: </strong>Type II GD presented in early infancy, with symptom onset from birth to 5 months of age (mean age at onset 2.8 ± 2.6 months) and was diagnosed between 5 and 9 months of age (mean 7.0 ± 2.3 months). Initial manifestations included cytopenias, splenomegaly, failure to thrive, and ichthyosiform dermatitis. Hepatomegaly was uncommon at onset, but hepatosplenomegaly was documented in all patients at diagnosis, followed by rapid neurological regression and death by 14 months of age. Type III GD had a mean age at onset of 2.3 ± 1.66 years and a mean age at diagnosis of 13.8 ± 16.87 years, reflecting substantial diagnostic delay. Oculomotor abnormalities were the most frequent presenting manifestations (83%). At diagnosis, all patients exhibited hepatosplenomegaly, cytopenias, and neurological involvement, while liver function remained preserved. Across both phenotypes, GBA1 variant combinations included genotypes predicted to result in very low or absent residual glucocerebrosidase activity, as well as genotypes predicted to retain some residual activity. Severe clinical courses were observed even in patients whose genotypes were predicted to retain residual enzyme activity, suggesting that predicted residual activity alone does not reliably explain clinical severity.</p><p><strong>Conclusions: </strong>In this Ukrainian cohort, neuronopathic GD demonstrated distinct clinical trajectories, with rapidly progressive infantile disease in type II and heterogeneous presentation with marked diagnostic delay in type III. Hepatosplenomegaly was a common systemic feature during disease progression, but should not be interpreted as an isolated stratifying sign. Its presence, particularly in combination with early or progressive neurological manifestations, should raise suspicion of neuronopathic GD.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906693","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":"Clinical and genetic profiles of postnatal patients with skeletal dysplasia in Guangxi during 8 years: a single-center experience.","authors":"Sheng Yi, Qi Yang, Linlin Wang, Xunzhao Zhou, Shujie Zhang, Jiale Qian, Shang Yi, Jing Huang, Junjie Chen, Qiang Zhang, Fei Chen, Jiao Li, Shengkai Wei, Xiaofei Zhang, Qinle Zhang, Pingshan Pan, Zailong Qin, Jingsi Luo","doi":"10.1186/s13023-026-04414-2","DOIUrl":"10.1186/s13023-026-04414-2","url":null,"abstract":"<p><strong>Background: </strong>Skeletal dysplasia (SD) is a clinically and genetically heterogeneous group of bone and cartilage disorders. Given the typically heterogeneous and nonspecific clinical manifestations associated with these conditions, molecular testing is essential to achieve a definitive diagnosis. To elucidate the clinical and mo^lecular characteristics of genetic skeletal disorders in the Guangxi region, we conducted a retrospective single-center study involving 434 families suspected of having SD who underwent molecular analysis in our department over an eight-year period. We analyzed their clinical and molecular genetic data.</p><p><strong>Results: </strong>Among our cohort, facial dysmorphism and short stature emerged as the most prevalent clinical manifestations, followed by growth delay and motor delay. Notably, molecular diagnoses were made at a relatively late age. Our findings revealed a total of 34 chromosomal abnormalities and 265 Mendelian genetic disorders. According to the Nosology of genetic skeletal disorders: 2023 revision, 75 genes were implicated in 199 positive molecular diagnoses, while the remaining 66 positive diagnoses were attributed to 56 causal genes. The most frequently identified causal gene was FGFR3, with the p.G380R substitution being the predominant pathogenic variant. The overall diagnostic yield through whole-exome sequencing was found to be 64.9%. Predictors of a positive molecular finding included short stature, calvaria abnormalities and knee deformities. Furthermore, the molecular diagnostic rate achieved through Sanger sequencing slightly exceeded that obtained via whole-exome sequencing.</p><p><strong>Conclusions: </strong>These findings have significantly enhanced the understanding of the clinical and genetic profiles of SD in Guangxi, elucidating the mutation spectrum of the associated causative genes. This study provides valuable clinical experience that can facilitate the effective implementation of genetic testing in the context of SD.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866262","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":"Interventions targeting challenges experienced by individuals with Pitt Hopkins syndrome: a scoping review.","authors":"Monika Dolik-Michno, Magnus Starbrink, Helena Wandin, Annika Jernberg Grönlund, Martha Gustavsson, Linn Johnels","doi":"10.1186/s13023-026-04561-6","DOIUrl":"10.1186/s13023-026-04561-6","url":null,"abstract":"<p><strong>Background: </strong>Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder with pronounced impacts on physical health and everyday functioning, including severe intellectual disability, impaired communication, epilepsy, and breathing dysregulation. Despite significant clinical challenges, there is limited evidence to guide interventions for individuals with PTHS. This scoping review aimed to examine the available literature on interventions targeting challenges experienced by individuals with PTHS and to identify gaps in the current knowledge base.</p><p><strong>Results: </strong>Sixteen peer-reviewed publications, published between 2012 and 2024, met the inclusion criteria. The majority of studies focused on medical management, predominantly addressing epilepsy and breathing abnormalities, and were pharmacological in nature. Most studies employed case report or small case series designs, and systematic outcome measurement approaches were rare. Epilepsy interventions largely reflected clinical practices in broader epilepsy populations, with common use of conventional antiseizure medications and evidence of potential benefit from newer agents in treatment-resistant cases. Non-pharmacological treatments, including vagus nerve stimulation, corpus callosotomy, ketogenic diet, and a walking-based mobility intervention, were described in only a few studies, with heterogeneous outcomes. Interventions for respiratory dysfunction, gastrointestinal symptoms, pain management, immune dysfunction, psychiatric or behavioral difficulties were limited and typically reported in individual cases. Research addressing psychosocial, behavioral, and participation-focused interventions was notably scarce, despite the broad functional impairments associated with PTHS.</p><p><strong>Conclusions: </strong>This scoping review shows that intervention research in PTHS remains at an early stage, with an evidence base dominated by descriptive case studies and few systematic evaluations. This limits the ability to formulate robust, evidence-based treatment recommendations. There is a need for more rigorous research designs in future research, that enable causal inference and systematic outcome measurement. Moreover, future studies should broaden the scope of intervention research to include communication, behavior, participation, physical activity and quality of life, alongside medical management, to better support the complex needs of individuals with PTHS. Increased focus on family impact and long-term outcomes may further enhance understanding and care strategies for this population.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840892","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":"Awareness, perceptions, and practices regarding transition to adult care for nephropathic cystinosis in Türkiye: a nationwide cross-sectional survey of pediatric nephrologists.","authors":"Yeşim Özdemir Atikel, Sevcan A Bakkaloğlu, Alev Yılmaz, Aslı Çelebi Tayfur, Aslı Kavaz Tufan, Aslıhan Kara, Ayşe Seda Pınarbaşı, Aysun Çaltık Yılmaz, Bahriye Atmış, Bedriye Nuray Alpman, Begüm Avcı, Burcu Yazıcıoğlu, Ece Demirci Bodur, Emre Leventoğlu, Erkin Serdaroğlu, Esra Nagehan Akyol Önder, Hülya Nalçacıoğlu, Kenan Yılmaz, Okan Akacı, Önder Yavaşcan, Özde Nisa Türkkan, Sare Gülfem Özlü, Seçil Arslansoyu Çamlar, Serra Sürmeli Döven, Songül Yılmaz, Yılmaz Tabel, Rezan Topaloğlu","doi":"10.1186/s13023-026-04557-2","DOIUrl":"10.1186/s13023-026-04557-2","url":null,"abstract":"<p><strong>Background: </strong>Nephropathic cystinosis is a rare multisystem disorder in which transition from pediatric to adult care is particularly a vulnerable period because of lifelong treatment demands and the need for sustained multidisciplinary follow-up. We aimed to assess awareness, perceptions, and self-reported transition practices among pediatric nephrologists in Türkiye caring for patients with nephropathic cystinosis.</p><p><strong>Methods: </strong>We conducted a nationwide descriptive cross-sectional web-based survey of pediatric nephrologists in Türkiye who had longitudinally followed at least one patient with nephropathic cystinosis. A 59-item questionnaire covering awareness, perceptions, and self-reported practices was administered via Google Forms, and responses were analysed descriptively at the item level.</p><p><strong>Results: </strong>In this nationwide descriptive cross-sectional web-based survey, 48 pediatric nephrologists participated. Respondents worked mainly in university hospitals (47.9%) and training and research hospitals (39.6%) and had a median of 14 years of pediatric nephrology experience (IQR 6-17). Although 66.7% distinguished transition from transfer, familiarity with cystinosis-specific transition models was limited; only 16.7% had ever applied a structured model and 8.3% reported a written transition plan in their center. The most frequently perceived challenges were treatment non-adherence (89.6%) and disruption of multidisciplinary follow-up (87.5%). Most respondents reported marked differences between pediatric and adult services, and the median recommended age for initiating transition planning was 17.5 years (IQR 17-18). Overall, 91.7% supported the development of a national transition model (58.3% considered it definitely necessary and 33.3% necessary but difficult to implement without external support).</p><p><strong>Conclusions: </strong>Among pediatric nephrologists in Türkiye, awareness of transition-related risks in nephropathic cystinosis was high, but structured transition practices were uncommon and initiation of transition planning was generally recommended at a later age than suggested by current guidance. These findings indicate an implementation gap and support the development of a feasible national transition framework that can be adapted to local resources.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195894","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":"Psychological symptoms in individuals with Spinal Muscular Atrophy (SMA) and their caregivers - results from a nation-wide study in Germany.","authors":"Justine Hussong, Berenike Leibrock, Tabea Huelle, Hannah Mattheus, Erik Landfeldt, Simone Thiele, Maggie C Walter, Michael Zemlin, Eva Moehler, Ulrich Dillmann, Marina Flotats-Bastardas","doi":"10.1186/s13023-026-04558-1","DOIUrl":"10.1186/s13023-026-04558-1","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the prevalence and associations of psychological symptoms in individuals with Spinal Muscular Atrophy (SMA) and their caregivers, utilizing data from a cross-sectional, observational assessment conducted in Germany. Participants were recruited through the national German SMA registry (June - September 2021), and psychological symptoms were assessed using validated measures such as the Strengths and Difficulties Questionnaire (SDQ) in children with SMA (n = 21) and the German Mini-Symptom-Checklist (Mini-SCL) in adults with SMA (n = 82) and caregivers (n = 67).</p><p><strong>Results: </strong>Results indicate that children with SMA exhibit lower rates of psychological symptoms compared to adults (9.5% vs. 13.4%), with internalizing symptoms (emotional problems, depression, anxiety) being the most prevalent in both age groups. Caregivers also demonstrate psychological symptoms in 14.9%, particularly those of individuals with SMA type 1. Symptom rates did not differ between groups with different motor function level. Significant correlations between caregiver and patient psychological symptoms were observed, while pharmacological treatment showed no significant impact on symptom rates.</p><p><strong>Conclusions: </strong>Psychological symptoms are common in individuals with SMA and their caregivers, particularly internalizing symptoms, underscoring the importance of routine psychological screening. Additionally, the correlation of patient and caregiver symptoms highlight the interplay between the mental health of both. These findings underscore the importance of integrating psychosocial care for both individuals with SMA and their caregivers to alleviate stress and promote well-being.</p><p><strong>Trial registration: </strong>German clinical trial register (DRKS), DRKS00022876. Registered 19 October 2020.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840926","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":"Correction: Caregiver-reported disease burden in Krabbe disease: evaluating outcomes of hematopoietic stem cell transplantation.","authors":"Nicholas Alexander Bascou, Skyler Jackson, Patti Engel, Anne Melchior, Paul Orchard, Stacy Pike-Langenfeld","doi":"10.1186/s13023-026-04480-6","DOIUrl":"10.1186/s13023-026-04480-6","url":null,"abstract":"","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813861","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":"Aspiration and silent aspiration in Niemann-Pick disease type C1: longitudinal findings from the NIH natural history study.","authors":"Beth I Solomon, Andrea M Munoz, Aiden Borruso, Ninet Sinaii, Nicole Farhat, Derek Alexander, Desiree A Labor, An Dang Do, Forbes D Porter","doi":"10.1186/s13023-026-04543-8","DOIUrl":"10.1186/s13023-026-04543-8","url":null,"abstract":"<p><strong>Background: </strong>Niemann-Pick disease type C1 (NPC1) is a rare neurodegenerative disorder in which dysphagia is common and aspiration pneumonia is a leading cause of mortality. Aspiration may be clinically apparent or silent, reflecting impaired airway sensation and protective reflexes. We aimed to characterize aspiration and silent aspiration in the National Institutes of Health (NIH) NPC1 Natural History Study (NCT00344331). We analyzed 130 participants with NPC1 enrolled between 2006 and 2024 who underwent speech-language pathology swallowing evaluations, including clinically indicated videofluoroscopic swallow studies (VFSS). Aspiration risk was rated using the NIH Penetration-Aspiration Scale (NIH-PAS). Silent aspiration was defined as aspiration on VFSS without cough, throat clearing, or wet vocal quality. Longitudinal models examined the presence of silent aspiration alone or (2) a NIH-PAS score > 1 (moderate-profound aspiration) or silent aspiration. Covariates included demographics, neurologic disease onset and duration, body weight/BMI, reflux and seizure medications, miglustat use, NPC Neurological Severity Score (NSS) 5-domain total and subscores (including swallow and respiratory), and the Annualized Severity Increment Score (ASIS).</p><p><strong>Results: </strong>Silent aspiration occurred in 24/130 (18.4%) participants. Among these, 50% demonstrated recurrent silent aspiration at subsequent visits, and 58.3% exhibited intermittent silent aspiration on follow-up. Considering aspiration risk, 27/130 (20.8%) had NIH-PAS > 1, including all silent aspirators. Silent aspiratiors alone had worse NIH-PAS, higher total NSS with poorer swallow, speech, ambulation, and fine-motor subscores, and higher ASIS. Patients with silent aspiration or NIH-PAS > 1 had an increased aspiration risk with longer neurologic symptom duration, seizure history, higher NSS, higher ASIS, and in children with lower weight percentile. Miglustat use was protective in the overall cohort, but not in the pediatric subgroup (< 20 years-old). Mean time to silent aspiration was ~ 10 years from neurologic symptom onset, with no difference by neurological disease onset.</p><p><strong>Conclusion: </strong>Silent aspiration is common in NPC1 and closely linked to advancing neurologic disease severity than to age-of-onset phenotype. Bedside clinical evaluations may underestimate silent aspiration; proactive longitudinal swallowing surveillance is warranted in individuals with higher NSS/ASIS scores, seizure history, pediatric weight decline, or evolving motor-speech impairment. These findings support incorporating overt and silent aspiration alongside swallowing function, into routine care and therapeutic trials.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888081","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":"Transplantation as disease modifying therapy in the era of gene therapy medicinal products - health policy considerations.","authors":"Margreet Wagenmakers, Anna Lehman, Caroline den Hoed, Laura van Dussen, Mirjam Langeveld, Sandra Sirrs","doi":"10.1186/s13023-026-04377-4","DOIUrl":"10.1186/s13023-026-04377-4","url":null,"abstract":"<p><strong>Background: </strong>New gene therapy medicinal products [GTMP] are being considered as alternatives to liver transplant [LTx] for some patients with inherited metabolic diseases [IMDs] but pose unique challenges for health policy makers.</p><p><strong>Methods: </strong>Published data on LTx and GTMP in human patients with urea cycle defects [UCD], glycogen storage disease type 1a [GSD1a], methylmalonic aciduria [MMA] and propionic aciduria [PA] were reviewed for efficacy, safety, data quality and health policy considerations.</p><p><strong>Results: </strong>LTx can reduce [MMA, PA] or eliminate [UCD, GSD1a] metabolic decompensation and improve quality of life. Risk of death peaks in the first year but long-term survival post LTx is similar to medical management. Initial data for GTMP show reduction in metabolic decompensation [MMA, PA, UCD] with more modest impacts in GSD1a. Long-term safety and efficacy data [available for LTx] may not be available at the time of market authorization for GTMP. Age is one health policy challenge as clinical trials for GTMP may target one age group but other age groups may request consideration for treatment. Quality concerns regarding data analysis exist for both modalities. Cost effectiveness of LTx is likely to be significantly more favorable than for GTMP. Access limitations are severe for both treatments, with high opportunity costs [price for GTMP, organ availability for LTx] mandating the need to engage the public as stakeholders in addition to patients, families, manufacturers and clinicians.</p><p><strong>Conclusions: </strong>LTx remains an effective treatment choice in the era of GTMP given the significant health policy challenges associated with these novel therapies.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725701","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":"Correction to: Quality of life in children and adults with epidermolysis bullosa: the QoL-REB explorative study.","authors":"Cinzia Pilo, Laura Benedan, Valentina Morra, El Hashem M, Gianluca Tadini, Giuseppina Annicchiarico, Michela Brena, Sophie Guez, Lucia Lospalluti, Isabella L C Mariani Wigley, Livio Provenzi, Paolo Mariani, Serena Barello","doi":"10.1186/s13023-026-04529-6","DOIUrl":"10.1186/s13023-026-04529-6","url":null,"abstract":"","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689457","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":"Expiratory phase lung mechanics in late-onset Pompe disease: a multicenter study using oscillometry to identify specific breathing abnormalities.","authors":"Grazia Crescimanno, Oreste Marrone, Marta Lazzeri, Paolo Innocente Banfi, Agata Lax, Elena Compalati, Rosario Di Marco, Sabrina Planiscig, Paola Confalonieri, Fabrizio Seidita, Filippo Brighina, Marco Confalonieri","doi":"10.1186/s13023-026-04532-x","DOIUrl":"10.1186/s13023-026-04532-x","url":null,"abstract":"<p><strong>Introduction: </strong>In late-onset Pompe disease (LOPD), muscle weakness causes restrictive lung impairment. In murine models, glycogen deposition in lung parenchyma suggests additional causes for restriction that remain poorly understood. We investigated whether oscillometry detects respiratory abnormalities not identified by spirometry and evaluated changes after air-stacking manoeuvres.</p><p><strong>Methods: </strong>We prospectively evaluated 16 adults with LOPD from three Italian centres. Alongside spirometry, oscillometry (at 5, 11, and 19 Hz) was performed to assess resistance (R) and reactance (X) across the breathing cycle and by respiratory phase. Measurements were repeated 5 min after an air-stacking manoeuvre.</p><p><strong>Results: </strong>Participants (7 men, 9 women; 51.6 ± 12.5 years) had moderate-to-severe restriction (FVC 53.3 ± 19.6% predicted) with preserved FEV1/FVC. Two oscillometric patterns emerged. The first one (seven patients) was characterised by an abnormal increase in expiratory resistance within breaths ([R5exp - R5insp] > 0.70 cmH₂O·s/L), associated or not with abnormal whole-breath R and intrabreath X changes. The second pattern (nine patients) consisted of normal R and X changes in the breathing cycle. Air-stacking increased FVC (53.3 ± 19.6 to 71.3 ± 19.2% predicted, p < 0.001) without normalising reactance.</p><p><strong>Conclusion: </strong>In LOPD, oscillometry detects distinct mechanical patterns not identified by spirometry. Air-stacking increases lung volumes without improving respiratory mechanics.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689480","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}