Orphanet Journal of Rare Diseases最新文献

{"title":"The effects of self-efficacy in managing the disease and disease adaptation levels of Familial Mediterranean Fever (fmf) patients on satisfaction with life: a web-based cross-sectional study.","authors":"Rahime Nur Demir, Ramazan Kiraç, Fatma Çiftçi Kiraç","doi":"10.1186/s13023-025-03931-w","DOIUrl":"https://doi.org/10.1186/s13023-025-03931-w","url":null,"abstract":"<p><strong>Background: </strong>Familial Mediterranean Fever (FMF) is an auto inflammatory disease often accompanied by fever and serositis attacks in which peritoneum, pleura, synovium, and rarely pericardium are spared. In the study, the effects of self-efficacy in managing the disease and disease adaptation levels of FMF patients on satisfaction with life were examined.</p><p><strong>Methods: </strong>This observational cross-sectional study was conducted using a web-based questionnaire sent via Facebook and Instagram FMF groups between February 1, 2024 and April 25, 2024. The population of this study consisted of patients diagnosed with FMF at least 1 year ago in Türkiye.</p><p><strong>Findings: </strong>The mean self-efficacy score of FMF patients in managing chronic diseases was found to be 4.67. According to the results of the study, physical adaptation was determined to be the highest adaptation in FMF patients. This is followed by psychological adaptation and social adaptation. In general, the scores the patients obtained regarding disease adaptation and its sub-dimensions were found to be close to the average value. The satisfaction with life scores of the patients were found to be below the average.</p><p><strong>Conclusion: </strong>This study revealed that the self-efficacy and disease adaptation levels of FMF patients in Türkiye affect their satisfaction with life.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"449"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963891","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":"Enzyme replacement therapy for the treatment of late onset Pompe disease: A systematic review and network meta-analysis.","authors":"Mark Corbett, Chinyereugo Umemneku-Chikere, Sarah Nevitt, Nyanar Jasmine Deng, Matthew Walton, Helen Fulbright, Chong Yew Tan, Robin Lachmann, Rachel Churchill, Robert Hodgson","doi":"10.1186/s13023-025-03981-0","DOIUrl":"10.1186/s13023-025-03981-0","url":null,"abstract":"<p><strong>Background: </strong>Late-onset Pompe disease (LOPD) is a rare inherited genetic condition caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. LOPD causes progressive muscle dysfunction and damage, leading to significant morbidity and early mortality. Enzyme replacement therapy (ERT) is the primary treatment for Pompe disease.</p><p><strong>Methods: </strong>A systematic review and network meta-analysis of published evidence on the clinical effectiveness of ERT and best supportive care (BSC) was undertaken to establish the relative effectiveness of ERT compared to BSC (in the absence of ERT). Bibliographic databases were searched to identify randomised controlled trials (RCTs) or any other prospective ERT studies in patients with Pompe disease. Network meta-analyses (NMA) of RCTs were undertaken to estimate indirect treatment effects for forced vital capacity (FVC) % predicted and the 6-minute walk test (6MWD). A narrative synthesis was employed to summarise other studies.</p><p><strong>Results: </strong>A total of 38 studies were included in the review. They comprised three RCTs, three RCT extension studies, seven registry studies and 25 single-group prospective studies. The results of two RCTs were judged to have a high risk of bias. In the NMA, after approximately one year, ERT-naïve patients showed significant 6MWD improvements vs. placebo: ~25 m with alglucosidase alfa and ~ 54 m with avalglucosidase alfa. No significant differences were found for FVC % predicted or comparisons with cipaglucosidase alfa, although very few ERT-naïve patients taking cipaglucosidase alfa were available for the analyses. Intra-ERT comparisons showed a significant 6MWD advantage for avalglucosidase alfa. However, a sensitivity analysis adjusting for skewed data revealed no significant differences. Long-term ERT effectiveness was assessed in single-group studies, showing initial gains maintained for 1-3 years, followed by gradual 10-15-year declines in 6MWD and FVC % predicted. However, small sample sizes and missing data introduce uncertainty.</p><p><strong>Conclusions: </strong>Our NMA results showed that ERTs lead to modest improvements in 6MWD after 1 year compared to placebo in ERT-naive populations. However, there is limited evidence supporting meaningful differences in outcomes between ERTs. There is a lack of longer-term follow-up data supporting the effectiveness of ERTs compared to each other and to best supportive care.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"451"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963871","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 course and management challenges in Lafora disease: a narrative analysis in an Apulian cohort.","authors":"Giuseppe d'Orsi, Maria Teresa Di Claudio, Antonella Liantonio, Paola Imbrici, Cosimo Damiano Altomare, Orazio Palumbo, Pietro Palumbo, Mario Benvenuto, Nicola Gambacorta, Graziano Lolli, Massimo Carella","doi":"10.1186/s13023-025-03976-x","DOIUrl":"https://doi.org/10.1186/s13023-025-03976-x","url":null,"abstract":"<p><strong>Background: </strong>Lafora disease (LD) is an ultra-rare, autosomal recessive neurodegenerative disorder characterized by the accumulation of Lafora bodies in the brain, leading to drug-resistant epilepsy, myoclonus, progressive dementia, and cerebellar dysfunction. This retrospective study describes the clinical course and management challenges of LD in a cohort of patients from the Apulia region of Southern Italy, where the disease prevalence appears to be higher than in other populations.</p><p><strong>Methods: </strong>We retrospectively analyzed clinical, electroencephalographic, and management data from six unrelated families with a confirmed diagnosis of LD, followed at the Neurology Unit of the Scientific Institute Casa Sollievo della Sofferenza Hospital between 2010 and 2024. Demographic information, clinical presentation, treatment history, disease progression, and outcomes were collected.</p><p><strong>Results: </strong>Our analysis identified three distinct electroclinical stages: an initial Presenting Symptoms Stage with the onset of seizures and subsequent development of myoclonus; a Progressive Neurodegeneration Stage characterized by drug-resistant epilepsy, dementia, and ataxia; and a Terminal Stage marked by severe disability, frequent seizure emergencies, and medical complications. Management in the late stages proved particularly challenging, requiring a multidisciplinary approach to address refractory seizures, status epilepticus, and medical complications such as aspiration pneumonia and respiratory failure. Home-based care, with specialized team support, played a crucial role in minimizing hospitalizations.</p><p><strong>Discussion: </strong>Our findings underscore the importance of early diagnosis and a multidisciplinary approach in the management of LD. The late stages of the disease are characterized by significant clinical challenges necessitating close collaboration among neurologists, epileptologists, and other healthcare professionals, supported by effective home-based care. The apparent higher prevalence in Apulia warrants further investigation into potential genetic or environmental factors.</p><p><strong>Conclusion: </strong>This study highlights the significant clinical burden of LD and emphasizes the importance of multidisciplinary management, particularly in the advanced stages. Home-based care supported by specialized teams and caregivers is essential for optimizing patient well-being. Further research is needed to identify early biomarkers and develop targeted therapies for this devastating condition.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"447"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963896","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":"Analysis of hydroxocobalamin dosage in patients with CblC deficiency.","authors":"Si Ding, Yuxin Deng, Yi Ding, Lili Hao, Wenjuan Qiu, Huiwen Zhang, Lili Liang, Ting Chen, Xia Zhan, Peng Xu, Chiju Yang, Hui Zou, Yongxing Chen, Shengnan Wu, Yufeng Wang, Min Yang, Xuefan Gu, Xianting Jiao, Lianshu Han","doi":"10.1186/s13023-025-03991-y","DOIUrl":"https://doi.org/10.1186/s13023-025-03991-y","url":null,"abstract":"<p><strong>Objective: </strong>cblC deficiency is the most common organic acidemia in China. Hydroxocobalamin (OHCbl) is the main important therapeutic approach, while no approved protocols on its dosage during stable periods exist. This study aims to analyze OHCbl dosage and explore its influencing factors, providing reference for the option of OHCbl dosage.</p><p><strong>Methods: </strong>A total of 730 patients with cblC deficiency during stable periods were enrolled. Univariate analysis and multiple linear regression analysis were used to investigate the correlation between OHCbl dosage and tandem mass spectrometry (MS/MS)-based newborn screening (NBS), disease onset as well as MMACHC gene mutation.</p><p><strong>Results: </strong>Univariate analysis revealed no significant difference in OHCbl dosage between whether patients were diagnosed by MS/MS-based NBS or not, while significant differences were found based on disease onset and the presence of c.482G > A variant. Multiple linear regression analysis further identified disease onset and the c.482G > A variant as independent factors influencing OHCbl dosage. The median OHCbl dosage during stable periods was 1.18 mg/kg/week, with 0.31 mg/kg/week in patients with the c.482G > A variant and 1.37 mg/kg/week in those without. However, in patients carrying the c.482G > A variant, there was no significant difference in the OHCbl dosage between those with and without disease onset, while in patients without the c.482G > A variant, those with disease onset had a higher OHCbl dosage compared to those without.</p><p><strong>Conclusion: </strong>The study demonstrated the independent influencing factors of OHCbl dosage in patients with cblC deficiency and put forward corresponding reference for the option of OHCbl dosage.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"448"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963904","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":"A rare cause of diffuse alveolar hemorrhage in a pediatric patient: thigh localization of INI1-deficient epithelioid sarcoma.","authors":"Xiaolei Tang, Zhipeng Zhao, Xingfeng Yao, Chunju Zhou, Shuai Gong, Haiming Yang","doi":"10.1186/s13023-025-03956-1","DOIUrl":"10.1186/s13023-025-03956-1","url":null,"abstract":"<p><strong>Background: </strong>Diffuse alveolar hemorrhage (DAH) is a group of rare but life-threatening conditions characterized by bleeding into the alveolar spaces, often associated with various etiologies. Epithelioid sarcoma (ES) is a rare and aggressive soft tissue sarcoma that has never been reported to be associated with DAH.</p><p><strong>Methods: </strong>We report a rare case of ES in a pediatric patient presenting with DAH and intracranial hemorrhagic lesions. Diagnostic evaluations included high-resolution chest CT (HRCT), bronchoscopy, brain MRI, lung biopsy, Positron emission tomography - computed tomography (PET-CT), and biopsy of a mass in the right thigh. Fluorescence in situ hybridization was performed to detect SMARCB1 (INI1) gene deletion.</p><p><strong>Results: </strong>A 13-year-old male presented with anemia and later developed hemoptysis with a decreased hemoglobin level. HRCT revealed bilateral ground-glass opacities consistent with DAH. Extensive autoimmune and infectious workups were all negative. Brain MRI demonstrated microhemorrhages. Despite corticosteroid therapy, the patient's condition worsened. PET-CT identified a hypermetabolic soft tissue mass in the right thigh, which on histopathological examination was confirmed as INI1-deficient ES. FISH analysis confirmed INI1 deletion.</p><p><strong>Conclusion: </strong>This case highlights the diagnostic challenges of INI1-deficient ES presenting with DAH and underscores the importance of considering malignancy in pediatric patients with atypical DAH. Multidisciplinary approaches, including advanced imaging and molecular diagnostics, are crucial for accurate diagnosis and management.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"445"},"PeriodicalIF":3.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883391","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":"Development of a conceptual model of early systemic sclerosis (scleroderma).","authors":"William R Lenderking, Mary Kathleen Ladd, Nicola Barnes, Julia Braverman, Maria Gasior, Jutta Hofmann, John-Phillip Lawo, Dinesh Khanna","doi":"10.1186/s13023-025-03917-8","DOIUrl":"10.1186/s13023-025-03917-8","url":null,"abstract":"<p><strong>Background: </strong>Systemic sclerosis (SSc) is a rare connective tissue disorder with heterogeneous manifestations. Two predominant subtypes, limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), are distinguished based on skin involvement distribution. A comprehensive conceptual SSc model is needed to support measurement strategies for outcome studies. This qualitative study aimed to explore key SSc disease concepts and develop a conceptual disease model capturing the heterogeneous lived experiences of patients with SSc.</p><p><strong>Methods: </strong>Patient- and clinician-reported concepts specific to dcSSc (more severe and faster-progressing than lcSSc) were identified via a targeted literature review and used to develop a preliminary dcSSc symptom model and a semi-structured qualitative interview guide. The guide was used in concept elicitation interviews with adults with lcSSc and dcSSc. A final conceptual SSc symptoms model was refined based on interview results.</p><p><strong>Results: </strong>Disease concepts were retrieved from 35 peer-reviewed articles and 17 clinical trials focusing on patients with dcSSc. The preliminary dcSSc symptom model included skin, hand, gastrointestinal, pain, joint, muscle, mouth, sexual, lung, cardiovascular, cognitive, ocular, and other symptoms. During concept elicitation interviews, participants (n = 44) reported 112 unique symptoms (within 13 domains). Twenty-six symptoms had not previously been identified in pertinent literature. Hand and skin symptoms were reported by all participants. Over 95% of participants reported at least one gastrointestinal and pain symptom, around 80% reported joint and mouth symptoms, 70% reported muscle symptoms, and over 50% reported ocular symptoms. Cognitive, lung, sexual, and cardiac symptoms were reported by fewer than half of participants. Participants with dcSSc reported a broader variety of symptoms than those with lcSSc. However, concepts relevant to patients with dcSSc and lcSSc strongly overlapped, suggesting that a single conceptual model is appropriate to map symptoms for both subtypes. The overlap was further reflected in the most bothersome symptoms, which included skin fibrosis and hand symptoms for both populations.</p><p><strong>Conclusions: </strong>The final conceptual model captures the heterogeneous symptoms of SSc and reflects the lived experience of patients with SSc. It covers both clinical SSc subtypes and can support the choice and/or development of instruments to measure patient experiences in clinical trials.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"446"},"PeriodicalIF":3.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883394","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":"A research roadmap for SCN8A-related disorders: addressing knowledge gaps and aligning research priorities across stakeholders.","authors":"","doi":"10.1186/s13023-025-03672-w","DOIUrl":"10.1186/s13023-025-03672-w","url":null,"abstract":"<p><strong>Background: </strong>Despite significant scientific progress since the 2012 discovery that variants in the SCN8A gene can cause human epilepsy, disease mechanisms and best practices for management of SCN8A-related disorders (SCN8A-RD) remain incompletely understood. To accelerate the rate of progress, the International SCN8A Alliance sponsored a conference in Boston, Massachusetts, on August 16-18, 2024. The goals were to identify core knowledge gaps and research priorities, and to establish a collaborative research strategy to improve quality of life. In addition to a number of family leaders representing caregiver priorities, the meeting included laboratory scientists, clinicians, and representatives from the biopharmaceutical industry.</p><p><strong>Main body: </strong>The scientific literature and requests for proposals from epilepsy funding agencies were reviewed prior to the meeting. Stakeholder-specific surveys were conducted focusing on knowledge gaps, research priorities, and scientific roadblocks. Interviews with biotechnology leaders were conducted to identify their priorities. These data were analyzed to assess responsiveness to caregiver concerns and to identify top research priorities for advancing the field. The Caregiver survey (n = 175) revealed top challenges and identified novel therapeutics and management of non-seizure phenotypes/comorbidities as top priorities. Clinician (n = 46) and scientist (n = 23) surveys identified a number of common research priorities, partially overlapping with caregiver concerns. Five core areas emerged from integrated analysis of all four stakeholder surveys and became the focus areas of five Working Groups: (1) Transformative Therapeutics, (2) Non-Seizure Outcomes, (3) Current Therapeutics, (4) Biomarkers, and (5) Whole Brain/Whole Body.</p><p><strong>Conclusions: </strong>Taking account of the concerns and priorities of the caregiver community, the five working groups identified research directions to address knowledge gaps that include both short- and long-term priorities to improve understanding of disease mechanisms and management for the spectrum of SCN8A-RD phenotypes. Challenges included identification of suitable funding mechanisms and the lack of expertise in certain methodologies and research areas. This Research Roadmap is expected to accelerate progress toward the goals of improved quality of life and transformative care for all those with SCN8A-RD.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"444"},"PeriodicalIF":3.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883392","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 molecular spectrum of patients with methylmalonic acidemia and homocysteinemia complicated by cardiovascular manifestations.","authors":"Wanqing Zhao, Yanan Zhang, Yalei Pi, Yuqian Li, Huifeng Zhang","doi":"10.1186/s13023-025-03907-w","DOIUrl":"10.1186/s13023-025-03907-w","url":null,"abstract":"<p><strong>Background: </strong>To investigate the clinical characteristics, treatment response, and prognosis of patients with methylmalonic acidemia (MMA) and homocysteinemia complicated by cardiovascular manifestations and to raise awareness regarding MMA and homocysteinemia.</p><p><strong>Methods: </strong>A total of 16 children diagnosed with MMA and homocysteinemia with cardiovascular manifestations who were admitted to the Department of Pediatrics of the Second Hospital of Hebei Medical University from June 2018 to October 2024 were retrospectively analyzed.</p><p><strong>Results: </strong>All 16 patients had varying degrees of neurological manifestations, and all had cardiovascular manifestations, 3 patients were diagnosed with MMA and homocysteinemia by newborn screening and received conventional treatment, the remaining 13 patients had nausea, vomiting, anemia, recurrent pneumonitis, respiratory distress, and lethargy as their first symptoms. Cardiovascular complications were found between the ages of 2 months and 12 years, with 9 patients having pulmonary hypertension, 7 having hypertension, and 5 having non-compaction of ventricular myocardium. Fourteen of these cases were confirmed to have CblC-type methylmalonic acidemia caused by mutations in the MMACHC gene by genetic testing. The most common mutations were c.80A > G (p.Q27R) (8 cases) and c.609G > A (p.W203X) (8 cases).</p><p><strong>Conclusion: </strong>Cardiovascular manifestation is uncommon in patients with MMA and homocysteinemia, but it is usually critical cause of death. When unexplained pulmonary hypertension or hypertension occurs, MMA and homocysteinemia should be suspected, especially when accompanied by manifestations of other systems.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"443"},"PeriodicalIF":3.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883393","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":"Experiences of symptom burden among young children born with esophageal atresia-tracheoesophageal fistula: a US focus group study.","authors":"Michaela Dellenmark-Blom, John Bennett, Rosella Micalizzi, Lianne Cole, Kaylee Woods, Lauren Cardoni, Leah Frain, Abdimajid Mohamed, Jessica Yasuda, Peter Ngo, Anke Widenmann, Graham Slater, Benjamin Zendejas","doi":"10.1186/s13023-025-03939-2","DOIUrl":"10.1186/s13023-025-03939-2","url":null,"abstract":"<p><strong>Background: </strong>Children born with esophageal atresia-tracheoesophageal fistula (EA-TEF) can suffer from aerodigestive morbidity that impairs their quality of life and can persist into adulthood. Ameliorating their symptom burden requires a thorough understanding of the symptom experiences that children have early in life. We aimed to explore parents' experiences of their children's aerodigestive symptom burden during the first years of life after being born with EA-TEF. This exploration also aimed to help determine whether a disease-specific measurement of symptom burden is needed.</p><p><strong>Method: </strong>Five standardized focus groups (FGs) with 22 parents of children with EA-TEF aged 6 months-7 years treated at a US tertiary pediatric surgical center were used to explore the children's symptom experiences. The FGs were audio-recorded, transcribed, content analyzed into what symptoms were expressed, together with their stated frequency, severity and relation to child distress.</p><p><strong>Results: </strong>Twenty-two parents made 450 unique statements about their children's aerodigestive symptom experiences. The respiratory symptoms (n = 170 statements, n = 21 parents) included the following unique symptom expressions; Breathing difficulties (n = 21), Breathing sounds (n = 6), Cough (n = 17), Mucus problems (n = 22), Prone to frequent or severe respiratory infections (n = 20) and Reduced physical capacity/strength (n = 8). The digestive symptoms (181 statements, n = 21 parents) encompassed symptom expressions of Acid reflux/heartburn (n = 7), Hiccups (n = 1), Nausea (n = 2), Reflux/food coming up (n = 10), Stomach problems (n = 4), Swallowing difficulties (n = 24) and Vomiting/throw-up (n = 6). The descriptions of respiratory and digestive symptom experiences included a variation of symptom frequency, severity and child distress. Furthermore, feeding difficulties (99 statements, n = 22 parents) included the children's Food refusal (n = 8), Need for mealtime adjustment (n = 7), Selective/restrictive eating (n = 14) and Upset/stress with feeds (n = 10). Most parents (n = 20, 91%) described that their children had symptom experiences that spanned all three categories (respiratory and digestive symptoms, feeding difficulties).</p><p><strong>Conclusions: </strong>Young children born with EA-TEF experience a significant symptom burden that can be reflected as a summative composite of the dimensions respiratory and digestive symptom frequency, severity and distress, in addition to feeding difficulties. This supports the need for a disease-specific measurement of symptom burden that is guided by the content and wording obtained directly from the parents' descriptions to help establish its content validity.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"438"},"PeriodicalIF":3.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874419","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":"Identification of three novel GNAO1 variants in a Chinese cohort with GNAO1 encephalopathy: expanding the clinical and genetic spectrum.","authors":"Daoqi Mei, Yu Gu, Bingbing Zhang, Shiyue Mei, Xiaona Wang, Yuanning Ma, Jie Deng, Jihong Tang","doi":"10.1186/s13023-025-03984-x","DOIUrl":"10.1186/s13023-025-03984-x","url":null,"abstract":"<p><strong>Objective: </strong>To summarize the clinical characteristics of a cohort of nine Chinese children with GNAO1 encephalopathy and analyze their genotypes.</p><p><strong>Methods: </strong>A retrospective study was conducted on nine children diagnosed with GNAO1 encephalopathy at the Neurology Department of two children's hospitals between January 2019 and December 2022. Their clinical manifestations, genetic test results, cranial imaging, electroencephalography and treatment were summarized. Their prognosis was followed up.</p><p><strong>Results: </strong>All nine patients presented with moderate-to-severe psychomotor developmental delay and dystonia. Six patients exhibited neonatal or infantile-onset epilepsy, manifesting as generalized tonic-clonic seizure, myoclonic seizure, epileptic spasms, and were diagnosed with developmental and epileptic encephalopathy 17 (DEE 17). Two patients presented with choreoathetosis in infancy without epileptic seizure and were diagnosed with the neurodevelopmental disorder with involuntary movements (NEDIM). One patient presented with choreoathetosis at two years of age and developed focal seizures at six years of age, representing an intermediate phenotype. During a follow-up period of 0.8-3.5 years, one child died due to infection. The remaining eight continued to exhibit psychomotor retardation. Pathogenic or likely pathogenic de novo heterozygous missense variants in GNAO1 were identified in all nine cases. Among these, the variants c.17G > T (p.Ser6Ile), c.119G > C (p.Gly40Ala), and c.748 C > T (p.Leu250Phe) are novel.</p><p><strong>Conclusion: </strong>In conclusion, we analyzed the clinical characteristics and genetic variants of a cohort of nine Chinese children with GNAO1 variants and identified three novel GNAO1 variants. Our study expanded the spectrum of genotypes and phenotypes in GNOA1-associated encephalopathy.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"440"},"PeriodicalIF":3.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874420","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}