Orphanet Journal of Rare Diseases最新文献

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CD126hi umbilical cord mesenchymal stem cells sensitive to IL-6 ameliorate inflammatory bowel disease by producing TGF-β1. 对IL-6敏感的CD126hi脐带间充质干细胞通过产生TGF-β1改善炎症性肠病。
IF 3.5 2区 医学
Orphanet Journal of Rare Diseases Pub Date : 2025-08-27 DOI: 10.1186/s13023-025-03993-w
Yanxia Fu, Bingchen Xie, Yinyin Wang, Jianqiu Sheng, Zhijie Chang, Xiaojue Qiu, Dongliang Yu, Junfeng Xu
{"title":"CD126<sup>hi</sup> umbilical cord mesenchymal stem cells sensitive to IL-6 ameliorate inflammatory bowel disease by producing TGF-β1.","authors":"Yanxia Fu, Bingchen Xie, Yinyin Wang, Jianqiu Sheng, Zhijie Chang, Xiaojue Qiu, Dongliang Yu, Junfeng Xu","doi":"10.1186/s13023-025-03993-w","DOIUrl":"https://doi.org/10.1186/s13023-025-03993-w","url":null,"abstract":"<p><strong>Background: </strong>Human umbilical cord mesenchymal stem cells (HUMSCs) are effective therapies for inflammatory bowel disease. However, the mechanisms remain unresolved. We found HUMSCs express CD126 (IL-6 receptor), which indicated CD126 sub-populations might show a distinct response to inflammation. In the present study, we explored whether CD126 is a critical molecule for HUMSCs in regulating inflammation.</p><p><strong>Methods: </strong>We assessed the regulatory effects of CD126 high (CD126<sup>hi</sup>) on the T lymphocyte subpopulations and related cytokines in the dextran sulfate sodium (DSS)-induced colitis model. The effect of CD126<sup>hi</sup> was evaluated by Hematoxylin and Eosin (H&E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Statistical significance was typically determined using Student's t-test or one-way analysis of variance (ANOVA) with Tukey test.</p><p><strong>Results: </strong>The disease symptoms were markedly ameliorated and the interleukin-6 (IL-6), interleukin-17 (IL-17), interferon-γ (IFN-γ), Tumor necrosis factor-α (TNF-α), and interleukin-4 (IL-4) levels were significantly reduced in DSS-treated mice administered with CD126<sup>hi</sup> HUMSCs but not in DSS-treated mice administered with CD126 low (CD126<sup>lo</sup>) HUMSCs. Intriguingly, CD126<sup>hi</sup> HUMSCs significantly increased the levels of transforming growth factor-β (TGF-β1) and interleukin-10 (IL-10) in DSS-treated mice, accompanied by an increase in regulatory T cells (Treg cells). In vitro experiments showed that CD126<sup>hi</sup> HUMSCs secreted TGF-β1 in response to IL-6 stimulation, while CD126<sup>lo</sup> HUMSCs were latent in the inflammatory environment. We considered that TGF-β1 secreted by CD126<sup>hi</sup> HUMSCs regulated the balance of Treg cells and thus promoted the recovery of murine colitis.</p><p><strong>Conclusion: </strong>Our results revealed a mechanism wherein CD126<sup>hi</sup> HUMSCs function as inflammatory sensors and secrete anti-inflammatory cytokines to rebalance the population of T cells. This study shed light on the potential therapeutic application of CD126<sup>hi</sup> HUMSCs for inflammatory diseases such as inflammatory bowel disease.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"458"},"PeriodicalIF":3.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963866","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}
引用次数: 0
Clinical characteristics and treatment outcomes in patients with Niemann-Pick disease type C (NP-C): a cross-sectional study. 尼曼-匹克病C型(NP-C)患者的临床特征和治疗结果:一项横断面研究
IF 3.5 2区 医学
Orphanet Journal of Rare Diseases Pub Date : 2025-08-27 DOI: 10.1186/s13023-025-03897-9
Parvaneh Karimzadeh, Farzad Ahmadabadi, Vahide Zeinali, Sharareh Kamfar, Mahmoud Reza Ashrafi, Ali Reza Tavasoli, Seyed Hassan Tonekaboni, Faezeh Ghanaati
{"title":"Clinical characteristics and treatment outcomes in patients with Niemann-Pick disease type C (NP-C): a cross-sectional study.","authors":"Parvaneh Karimzadeh, Farzad Ahmadabadi, Vahide Zeinali, Sharareh Kamfar, Mahmoud Reza Ashrafi, Ali Reza Tavasoli, Seyed Hassan Tonekaboni, Faezeh Ghanaati","doi":"10.1186/s13023-025-03897-9","DOIUrl":"https://doi.org/10.1186/s13023-025-03897-9","url":null,"abstract":"<p><strong>Background: </strong>Niemann-Pick disease type C (NP-C) is a rare autosomal recessive lysosomal storage disorder characterized by progressive neurodegeneration. This study aimed to characterize the clinical features and treatment outcomes of NP-C in Iranian patients.</p><p><strong>Methods: </strong>We conducted a cross-sectional study of 58 patients with NP-C diagnosed between March 2013 and March 2024 at Mofid Children's Hospital, Tehran. Clinical manifestations were categorized into visceral, cortical, and deep brain domains. Treatment outcomes were assessed in 52 patients who received miglustat therapy.</p><p><strong>Results: </strong>The mean age at disease onset was 3.35 ± 3.40 years, with diagnosis occurring at 7.03 ± 4.60 years. Filipin staining confirmed diagnosis in 96.6% of cases. Following miglustat therapy (mean duration: 1.96 ± 2.54 years), 86.5% of patients remained stable or showed improvement in at least one disease domain. Visceral manifestations showed the most favorable response, with 30.8% of patients demonstrating improvement in hepatosplenomegaly. Cortical manifestations (seizures and cognitive disorders) improved in 13.5% of patients. Motor function remained stable in 63.5% of patients, while 7.7% experienced deterioration. Ocular manifestations remained largely stable (94.2%). Seven patients (13.5%) experienced deterioration in at least one domain. At study completion, mortality was 20.7%, with mean age at death of 11.58 ± 7.73 years.</p><p><strong>Conclusion: </strong>This first comprehensive analysis of NP-C in Iran demonstrates the effectiveness of miglustat across multiple disease manifestations, particularly for visceral and cortical symptoms. While neurological symptoms generally stabilized, responses varied, emphasizing the need for individualized therapeutic approaches. Early diagnosis and intervention remain crucial for improving outcomes in this progressive neurodegenerative disorder.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"459"},"PeriodicalIF":3.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963885","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}
引用次数: 0
Health-related quality of life of adults with generalized pustular psoriasis in Malaysia: a cross-sectional study. 马来西亚成人广泛性脓疱性牛皮癣患者的健康相关生活质量:一项横断面研究
IF 3.5 2区 医学
Orphanet Journal of Rare Diseases Pub Date : 2025-08-27 DOI: 10.1186/s13023-025-03820-2
Xin Qian Seah, Siew Chin Ong, Mustapha Mohammed, Mei Ee Tay, Latha Selvarajah, Wooi Chiang Tan, Sook Yee Michelle Voo, Yen Loo Ting, Jyh Jong Tang, Azura Mohd Affandi
{"title":"Health-related quality of life of adults with generalized pustular psoriasis in Malaysia: a cross-sectional study.","authors":"Xin Qian Seah, Siew Chin Ong, Mustapha Mohammed, Mei Ee Tay, Latha Selvarajah, Wooi Chiang Tan, Sook Yee Michelle Voo, Yen Loo Ting, Jyh Jong Tang, Azura Mohd Affandi","doi":"10.1186/s13023-025-03820-2","DOIUrl":"10.1186/s13023-025-03820-2","url":null,"abstract":"<p><strong>Background: </strong>Generalized Pustular Psoriasis (GPP) is a rare but severe form of psoriasis, characterized by flares involving the sudden spread of erythema with sterile pustules, crusting, and scaling.</p><p><strong>Objective: </strong>The study aimed to assess both generic and dermatology-specific health-related quality of life (HRQoL) in patients with GPP across flare and non-flare stages in Malaysia.</p><p><strong>Methods: </strong>The study was a multicenter cross-sectional study conducted among patients diagnosed with GPP attending the General Hospitals under the Ministry of Health, Malaysia, between May 15, 2024, and November 30, 2024. The HRQoL of the GPP patients were assessed using the validated versions of the Dermatology Life Quality Index (DLQI) and EuroQol-5 Dimensions (EQ-5D). Data were statistically analysed using descriptive and inferential statistics using IBM SPSS version 28.0.</p><p><strong>Results: </strong>A total of fifty-four patients from six centres were enrolled into the study, with a mean (standard deviation, SD) age of 44.6 (SD: 15.5), the majority being female (n = 41, 75.9%). The mean (SD) scores of the DLQI and EQ-5D for the patients with GPP were 8.44 (SD: 7.12) and 0.74 (SD: 0.27), respectively. Thirteen patients (24%) were in their flares phase at the time of assessment. During the flares stage, patients experienced poorer quality of life, as indicated by a significantly higher mean DLQI score of 15.70 (SD: 7.33) (p < 0.001), lower EQ-5D score of 0.41 (SD: 0.30) (p < 0.001), and an EQ-VAS score of 51.15 (SD: 19.70) (p = 0.006), compared to those with non-flares. Patients' flare status was a significant predictor of impaired HRQoL based on DLQI (p = 0.004), EQ-5D (p < 0.001) and EQ-VAS (p < 0.001) while higher BMI was associated with impaired EQ-VAS score (p = 0.001).</p><p><strong>Conclusion: </strong>The study demonstrates the substantial and dynamic burden of GPP, with a significant impairment in HRQoL among the patients in Malaysia, particularly during disease flares. These findings suggest the importance of prioritizing flares prevention and addressing the holistic needs of GPP patients to maximize their quality of life over the long term.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"460"},"PeriodicalIF":3.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963936","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}
引用次数: 0
Clinical features and genetic analysis of A20 haploinsufficiency. A20单倍体功能不全的临床特征及遗传分析。
IF 3.5 2区 医学
Orphanet Journal of Rare Diseases Pub Date : 2025-08-26 DOI: 10.1186/s13023-025-04004-8
Fumin Xue, Chao An, Zhi Lei, Shijie Dong, Yaqiong Guo, Jiangshan Hou, Jing Yu, Yuesheng Wang
{"title":"Clinical features and genetic analysis of A20 haploinsufficiency.","authors":"Fumin Xue, Chao An, Zhi Lei, Shijie Dong, Yaqiong Guo, Jiangshan Hou, Jing Yu, Yuesheng Wang","doi":"10.1186/s13023-025-04004-8","DOIUrl":"https://doi.org/10.1186/s13023-025-04004-8","url":null,"abstract":"<p><strong>Objective: </strong>To described clinical and genetic characteristics of 4 patients presenting A20 haploinsufficiency (HA20) treated at Children's hospital affiliated to Zhengzhou university from 2015 to 2024.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on the clinical data, genetic testing results, and treatment outcomes of four children with HA20 treated at the Children's hospital affiliated to Zhengzhou university from 2015 to 2024.</p><p><strong>Results: </strong>All four patients developed symptoms before the age of 1 year, presenting with recurrent fever and abdominal pain with diarrhea. Most common characteristics were hematochezia, bipolar aphthosis, arthritis, skin eruption in 50% of patients. Lab tests revealed elevated inflammatory markers; all patients had anemia. Imaging showed intestinal mucosal edema, hip/knee joint effusions, and lymphadenopathy in one case. Endoscopy revealed gastrointestinal aphthosis in 100% of cases. Genetic testing identified TNFAIP3 mutations in all four patients, including one novel whole-gene deletion (6q23.3chr6:136700000-138880000), 2 novel pathogenic mutations (c.866delA, c.1243_1247del), and one previously reported mutation (c.133C > T). Treatment included exclusive enteral nutrition (EEN) and thalidomide for all patients. One patient was switched to infliximab (IFX) combined with azathioprine due to gastrointestinal side effects, and one patient received methylprednisolone during acute phase. Follow-up for 4-10 years showed that 1 patient had improved symptoms with IFX and azathioprine but still had intermittent fever and perianal aphthosis; While one patient demonstrated poor response to EEN-thalidomide therapy requiring regimen change, the other responded well. One patient exhibited normalized gastrointestinal function following EEN-thalidomide therapy, yet still required repeated hospitalizations for recurrent infections with progressively prolonged inter-episode intervals.</p><p><strong>Conclusion: </strong>HA20 has strong clinical heterogeneity, and genetic testing is crucial for diagnosis and guiding treatment. Early diagnosis and individualized treatment can improve prognosis.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"457"},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963893","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}
引用次数: 0
The impact of vanishing white matter on unaffected family members. 白质消失对未受影响的家庭成员的影响。
IF 3.5 2区 医学
Orphanet Journal of Rare Diseases Pub Date : 2025-08-26 DOI: 10.1186/s13023-025-03987-8
Romy J van Voorst, Daphne H Schoenmakers, Irene van Beelen, Francesco Gavazzi, Alexandra Chapleau, Adeline Vanderver, Geneviève Bernard, Ingeborg Krägeloh-Mann, Marjo S van der Knaap
{"title":"The impact of vanishing white matter on unaffected family members.","authors":"Romy J van Voorst, Daphne H Schoenmakers, Irene van Beelen, Francesco Gavazzi, Alexandra Chapleau, Adeline Vanderver, Geneviève Bernard, Ingeborg Krägeloh-Mann, Marjo S van der Knaap","doi":"10.1186/s13023-025-03987-8","DOIUrl":"https://doi.org/10.1186/s13023-025-03987-8","url":null,"abstract":"<p><strong>Background: </strong>Vanishing White matter (VWM) is one of the more prevalent leukodystrophies, caused by biallelic pathogenic variants in any of the EIF2B1-5 genes. It is characterized by chronic progressive neurological deterioration and additional stress-provoked episodes of rapid decline, leading to severe neurological impairment and early death. The impact of VWM on unaffected family members has not been investigated.</p><p><strong>Methods: </strong>This international cross-sectional study enrolled parents, partners, and unaffected siblings. We used online administration of (1) health-related quality of life questionnaires (quantitative, comprising the EuroQol-5-Dimensions [EQ5-D]-5-Levels questionnaire [EQ-5D-5L], EuroQol-5-Dimensions-Youth-3-Levels questionnaire [EQ-5D-Y-3L], Pediatric Quality of Life Family Impact Module [PedsQL™-FIM], PedsQL™ Child-Adult Self Report [PedsQL™-SC]); (2) VWM-specific customized questionnaires (quantitative, comprising the impact of VWM inventory questionnaires for parents, partners and siblings); and (3) in-depth semi-structured interview (qualitative).</p><p><strong>Results: </strong>A total of 100 family members were included: 52 mothers, 29 fathers, 13 unaffected siblings, and 6 partners. Mothers and partners scored significantly poorer on the EQ5D-5L than the reference norms. Fathers and mothers scored significantly poorer on the PedsQL™-FIM than the reference norms. Siblings scored similar to the reference norms on the EQ5D-5L and all domains of the PedsQL™-SC, with the lowest score on the emotional domain. Qualitative interviews revealed three main drivers of the impact of VWM: (1) lack of knowledge and empathy of healthcare professionals, (2) unpredictable disease course, and (3) caregiver responsibilities. Mothers reported substantial impacts on their emotional well-being and dissatisfaction with their professional development. Fathers commonly reported financial concerns and heightened family responsibility. Partners mentioned emotional exhaustion and difficulty in managing family responsibilities. Siblings frequently reported internal struggles, finding it challenging to express their feelings.</p><p><strong>Conclusions: </strong>Mothers and partners indicate a significant and consistent reduction in their quality of life on standardized questionnaires. Qualitative interviews revealed in-depth details of VWM's impact on all family members. Improved healthcare communication, symptom management resources, and support networks are essential for alleviating VWM's impact on families. This study emphasizes the importance of tailored approaches to supporting family members of VWM patients and enhancing their quality of life.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"456"},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963924","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}
引用次数: 0
Cutaneous manifestations-associated with tuberous sclerosis complex and the use of topical rapamycin in the United States: a sub-analysis of an international survey of caregivers and patients. 在美国,与结节性硬化症相关的皮肤表现和局部雷帕霉素的使用:一项对护理人员和患者的国际调查的亚分析。
IF 3.5 2区 医学
Orphanet Journal of Rare Diseases Pub Date : 2025-08-25 DOI: 10.1186/s13023-025-03653-z
Sreedevi Boggarapu, Gabrielle Rushing, Ashley Pounders, Steven L Roberds, Eric Beresford
{"title":"Cutaneous manifestations-associated with tuberous sclerosis complex and the use of topical rapamycin in the United States: a sub-analysis of an international survey of caregivers and patients.","authors":"Sreedevi Boggarapu, Gabrielle Rushing, Ashley Pounders, Steven L Roberds, Eric Beresford","doi":"10.1186/s13023-025-03653-z","DOIUrl":"https://doi.org/10.1186/s13023-025-03653-z","url":null,"abstract":"<p><strong>Background: </strong>This analysis was aimed to characterize cutaneous manifestations associated with tuberous sclerosis complex (TSC) and management of facial angiofibroma in the United States from a patient/caregiver perspective. Data was collected from an international survey of TSC Alliance conducted during May-June 2017 by distributing a link to patients/caregivers through various channels including social media.</p><p><strong>Results: </strong>Of the 418 caregivers and 133 patients, 336 (80.0%) caregivers and 98 (73.7%) patients reported cutaneous manifestations. Increased incidence in cutaneous manifestations was observed with age with the highest incidence in the age group spanning 27-45 years. More than half of the responders reported minor, moderate or major changes to their lifestyle because of the impact of cutaneous manifestations on the quality of life. The presence of other TSC-related manifestations studied in this survey (epilepsy, non-malignant brain tumours, developmental delay, learning or memory issues, kidney issues, communication issues, behavioural issues, sleep problems, anxiety or depression, heart issues, eye issues, dental issues, bone or skeletal issues, lung issues, and liver or pancreatic issues) was significantly higher in patients with cutaneous manifestations. Surgical removal was reported by 28.6% caregivers and 61.2% patients. Compounded topical rapamycin use for the management of facial angiofibroma was reported by 31.3% caregivers/23.5% patients, out of whom, improvement in skin condition was reported by 64.8% caregivers/69.6% patients. Overall, 82.9% of caregivers and 73.9% patients reported improvement as moderately effective or very effective.</p><p><strong>Conclusions: </strong>In patients with cutaneous manifestations, a higher frequency of other TSC manifestations was observed. Presence of cutaneous manifestations impacted the quality of life of more than half of the responders. Surgical removal of cutaneous manifestations and compounded topical rapamycin treatment for the management of facial angiofibroma were reported. Compounded topical rapamycin use for the management of facial angiofibroma was reported as moderately effective or very effective by most of the responders.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"455"},"PeriodicalIF":3.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963928","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}
引用次数: 0
Clinical, biochemical, and molecular characteristics of Sanfilippo a syndrome (MPS IIIA) in a cohort of Egyptian patients. 临床,生化和分子特征的三filippo综合征(MPS IIIA)在一组埃及患者。
IF 3.5 2区 医学
Orphanet Journal of Rare Diseases Pub Date : 2025-08-25 DOI: 10.1186/s13023-025-03971-2
Ekram Fateen, Soha S Nosier, Nahla N Abdel Aziz, Amira M Radwan, Eman E A Mohammed
{"title":"Clinical, biochemical, and molecular characteristics of Sanfilippo a syndrome (MPS IIIA) in a cohort of Egyptian patients.","authors":"Ekram Fateen, Soha S Nosier, Nahla N Abdel Aziz, Amira M Radwan, Eman E A Mohammed","doi":"10.1186/s13023-025-03971-2","DOIUrl":"https://doi.org/10.1186/s13023-025-03971-2","url":null,"abstract":"<p><strong>Background: </strong>Lysosomal storage diseases (LSDs) is a large group of genetically heterogeneous inherited metabolic disorders that affect the functions of the lysosomes in various human tissues. Mucopolysaccharidosis type IIIA (MPSIIIA), Sanflippo syndrome A, is a rare autosomal recessive LSD caused by biallelic variants in the SGSH gene, codes for the lysosomal enzyme heparan-N-sulphatase. This study aimed to find out the SGSH mutational spectrum, clinical and biochemical characteristics in a cohort of MPS IIIA Egyptian patients.</p><p><strong>Results: </strong>Ten patients derived from 9 unrelated families, clinically and biochemically diagnosed having MPS IIIA secondary to heparan sulphatase deficiency, were enrolled. Patients, variably, displayed early-onset and progressive neurological and mental deterioration, aggressive and hyperactive behaviors, sleep disturbances and visceromegaly. Sanger sequencing of the SGSH coding and exon-intron boundaries revealed four homozygous disease-causing variants in all the patients (100%), three previously reported (p.Y224*, p.R377C, and p.V361Sfs*52), and a novel one (c.948delA; p.D317Tfs*96). The p.Y224* in exon 6 was the most recurrent variant (5/10, 50%), followed by the missense R377C in exon 8 (3/10; 30%), while the two frameshift truncating variants, each appeared in only one patient; presenting 10% of the disease causing variants.</p><p><strong>Conclusions: </strong>The pattern of variants recurrence in unrelated Egyptian patients highlights exons 6 and 8 as hot spots for first variant screening. The molecular findings of this study expand the SGSH variant spectrum and underline specific exons for first screening of MPS IIIA patients, which would largely help the early diagnosis and genetic counselling. To the best of our knowledge, the present study is the first delineating the SGSH variant profile in Egyptian Sanflippo A patients.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"454"},"PeriodicalIF":3.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963938","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}
引用次数: 0
Alpha-lipoic acid supplementation improves pathological alterations in cellular models of Friedreich ataxia. 补充α -硫辛酸可改善弗里德赖希共济失调细胞模型的病理改变。
IF 3.5 2区 医学
Orphanet Journal of Rare Diseases Pub Date : 2025-08-23 DOI: 10.1186/s13023-025-03990-z
Marta Talaverón-Rey, Diana Reche-López, Suleva Povea-Cabello, Mónica Álvarez-Córdoba, David Gómez-Fernández, Ana Romero-González, Paula Cilleros-Holgado, José Manuel Romero-Domínguez, Alejandra López-Cabrera, Rocío Piñero-Pérez, Susana González-Granero, José Manuel García-Verdugo, José A Sánchez-Alcázar
{"title":"Alpha-lipoic acid supplementation improves pathological alterations in cellular models of Friedreich ataxia.","authors":"Marta Talaverón-Rey, Diana Reche-López, Suleva Povea-Cabello, Mónica Álvarez-Córdoba, David Gómez-Fernández, Ana Romero-González, Paula Cilleros-Holgado, José Manuel Romero-Domínguez, Alejandra López-Cabrera, Rocío Piñero-Pérez, Susana González-Granero, José Manuel García-Verdugo, José A Sánchez-Alcázar","doi":"10.1186/s13023-025-03990-z","DOIUrl":"https://doi.org/10.1186/s13023-025-03990-z","url":null,"abstract":"<p><strong>Background: </strong>Friedreich ataxia (FRDA), the most common autosomal recessive ataxia, is characterized by degeneration of the large sensory neurons and spinocerebellar tracts, cardiomyopathy, and an increased incidence of diabetes. The underlying pathophysiological mechanism of FRDA, driven by a significantly decreased expression of frataxin (FXN), involves increased oxidative stress, reduced activity of enzymes containing iron‑sulfur clusters, defective energy production, calcium dyshomeostasis, and impaired mitochondrial biogenesis, leading to mitochondrial dysfunction.</p><p><strong>Methods: </strong>This study is aimed at evaluating the role of alpha-lipoic acid (ALA) in reversing the pathological alterations in fibroblasts and induced neurons derived from FRDA patients. Iron accumulation, lipid peroxidation, transcript and protein expression levels of frataxin, mitochondrial proteins, as well as mitochondrial bioenergetics were examined.</p><p><strong>Results: </strong>Treatment with ALA was able to correct partially the pathological alterations in mutant fibroblasts. The optimal ALA concentration was dependent on the number of expanded GAA triplet repeats in the FXN gene. The positive effect of ALA was also confirmed in induced neurons derived from FRDA mutant fibroblasts. Our results also suggest that the positive effect of ALA was mediated by Peroxisome Proliferator-Activated Receptor Gamma activation.</p><p><strong>Conclusions: </strong>Our results suggest that ALA treatment can increase the expression levels of frataxin and reverse the mutant phenotype in cellular models of FRDA.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"453"},"PeriodicalIF":3.5,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963811","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}
引用次数: 0
Psychometric evaluation of novel hyperphagia questionnaires in a real-world setting for patients with a rare MC4R pathway disease. 一种罕见的MC4R通路疾病患者在现实世界中新型贪食问卷的心理测量评估
IF 3.5 2区 医学
Orphanet Journal of Rare Diseases Pub Date : 2025-08-22 DOI: 10.1186/s13023-025-03948-1
Jeremy Pomeroy, Usha G Mallya, Min Yang, Caroline Huber, Alexandra Greatsinger, Ella Hagopian, Andrea M Haqq
{"title":"Psychometric evaluation of novel hyperphagia questionnaires in a real-world setting for patients with a rare MC4R pathway disease.","authors":"Jeremy Pomeroy, Usha G Mallya, Min Yang, Caroline Huber, Alexandra Greatsinger, Ella Hagopian, Andrea M Haqq","doi":"10.1186/s13023-025-03948-1","DOIUrl":"https://doi.org/10.1186/s13023-025-03948-1","url":null,"abstract":"<p><strong>Background: </strong>There are no validated measures to assess hyperphagia associated with rare MC4R pathway diseases, such as Bardet-Biedl Syndrome (BBS). Symptoms of Hyperphagia© (SoH) and Impacts of Hyperphagia© (IoH) are novel questionnaires designed to assess signs and symptoms of hyperphagia and their impacts on patients and caregivers. We evaluated the psychometric performance of the caregiver-versions of the SoH: Caregiver (Observer-reported) and IoH: Caregiver (Observer-reported and Self-reported subscales).</p><p><strong>Results: </strong>Reliability and validity were evaluated using data from a multi-country cross-sectional survey of adult caregivers of patients with BBS experiencing hyperphagia and obesity. Other instruments included were Impact of Weight on Quality of Life (IWQOL)-Kids (Parent Proxy), PROMIS Scale Global Health of Caregiver, Revised Impact on Family Scale (RIOFS), and Work Productivity and Activity Impairment. 242 eligible caregivers completed the survey. Exploratory factor analysis identified 1 factor per subscale. Strong internal consistency was observed for IoH: Caregiver (Observer) (Cronbach's a = 0.66) and IoH: Caregiver (Self) (a = 0.72) and moderate for SoH: Caregiver (Observer) (a = 0.40). Moderate-to-strong correlations were observed with school days missed and all domains of IWQOL-Kids except Physical Comfort (range = 0.315-0.573, p's < 0.001). Known-groups indicated significantly worse SoH: Caregiver subscores for patients using appetite suppressants or implementing more weight management approaches (6-10 vs. ≤5 or > 10). Caregivers reporting greater strain on RIOFS items and worse mental health had worse IoH subscores.</p><p><strong>Conclusions: </strong>The SoH: Caregiver and IoH: Caregiver demonstrated preliminary validity, reliability, and consistency in a real-world setting. Research is underway to further validate these measures for use in clinical trials for BBS and other MC4R pathway-related diseases associated with obesity.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"452"},"PeriodicalIF":3.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963864","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}
引用次数: 0
Identity development and adaptation in adolescents with genetic conditions: a qualitatively oriented mixed-methods study to develop strategies for optimizing clinical genetics services. 具有遗传条件的青少年的身份发展和适应:一项定性导向的混合方法研究,以制定优化临床遗传学服务的策略。
IF 3.5 2区 医学
Orphanet Journal of Rare Diseases Pub Date : 2025-08-21 DOI: 10.1186/s13023-025-03968-x
Tasha Wainstein, Cyrus Boelman, Connie Ens, William T Gibson, Kevin Gregory-Evans, Olubayo U Kolawole, Sheila K Marshall, Kathryn Selby, Jehannine Austin, Alison M Elliott
{"title":"Identity development and adaptation in adolescents with genetic conditions: a qualitatively oriented mixed-methods study to develop strategies for optimizing clinical genetics services.","authors":"Tasha Wainstein, Cyrus Boelman, Connie Ens, William T Gibson, Kevin Gregory-Evans, Olubayo U Kolawole, Sheila K Marshall, Kathryn Selby, Jehannine Austin, Alison M Elliott","doi":"10.1186/s13023-025-03968-x","DOIUrl":"10.1186/s13023-025-03968-x","url":null,"abstract":"<p><strong>Background: </strong>Genetic counselling for adolescents necessitates an approach distinct from that used with adults. Developing best practices is crucial, considering the growing number of disabled adolescents worldwide and increasing use of genomic testing early in life. We investigated perceptions of adolescents (10-19 years) who had been diagnosed with a genetic disorder in terms of how they describe receiving, understanding, and living with a genetic condition. We undertook a cross-sectional, qualitatively oriented mixed methods study underpinned by the pragmatic paradigm. Adolescents completed two self-report measures - the psychological adaptation scale (PAS) and the illness identity questionnaire (IIQ)-and participated in semi-structured interviews. Demographic, PAS, and IIQ data were analyzed using descriptive statistics. We used phronetic iterative analysis to interrogate interview data. Qualitative and quantitative components were integrated through abduction.</p><p><strong>Results: </strong>Eighteen participants (median age: 15.5 years; 11/18 women/girls; 13/18 typical cognition; 8/18 de novo presentation) with a variety of genetic conditions participated. Participants had a mean PAS of 3.07 ± 0.84 indicating adequate adaptation. Their IIQ profiles indicated slightly better mean adaptive scores (3.10 ± 1.06) than mean maladaptive scores (2.85 ± 0.99). We developed a conceptual model that describes disability and genetic identity development and psychological adaptation among participants composed of three interacting components: internalizing processes; variability arising from contextual factors; and external factors associated with the processes. Adolescents generally moved among four internalizing processes (initiating, minimizing, exploring, and accepting). Movement across these processes took place frequently because of contextual factors like setting and disability type. Communication and engagement with caregivers, peers, and healthcare professionals, social interactions with others who have the same or a similar condition, and the impact of ableism constituted the main external factors with which adolescents engaged in the development of these identities.</p><p><strong>Conclusions: </strong>Our findings present a foundation upon which to develop a care model optimized for the needs of adolescents with genetic conditions. Enhancing access to genetic counselling as a means of facilitating identity development is an important component of these care models.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"450"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963908","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}
引用次数: 0
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