Orphanet Journal of Rare Diseases最新文献

{"title":"Clinical, biochemical and genetic characteristics of patients with argininosuccinate lyase deficiency from a single center cohort in China.","authors":"Kaichuang Zhang, Deyun Lu, Lili Liang, Yi Yang, Ruifang Wang, Yuning Sun, Zhuwen Gong, Haijuan Zhi, Wenjuan Qiu, Lianshu Han","doi":"10.1186/s13023-025-04026-2","DOIUrl":"https://doi.org/10.1186/s13023-025-04026-2","url":null,"abstract":"<p><strong>Background: </strong>Argininosuccinate lyase deficiency (ASLD) is a rare autosomal recessive urea cycle disorder (UCD) resulting from mutations in the ASL gene. Previous studies of ASLD in patients from China have predominantly been limited to individual case reports, lacking comprehensive cohort study. This study aimed to systematically evaluate the clinical features, biochemical abnormalities, and genetic mutations of Chinese ASLD patients, thereby enhancing the understanding of the unique characteristics of this population.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of clinical and genetic data from patients diagnosed with ASLD at Shanghai Xinhua Hospital between January 2011 and May 2024.</p><p><strong>Results: </strong>The cohort consisted of 28 Chinese ASLD patients from Xinhua Hospital. The median age of symptom onset was 18 days (range: 2 days to 6 years). Five patients (17.9%) died within the first year, and 87.0% (20/23) of survivors exhibited developmental delay. Citrulline levels were elevated in all patients. 14 out of 16 (87.5%) who underwent platelet testing demonstrated elevated platelet counts. The median blood ammonia level was 172 µmol/L (range: 9-1911 µmol/L). Early-onset cases had significantly higher ammonia levels than late-onset cases ( P < 0.0001). Eight patients underwent liver transplantation, which normalized ammonia levels and liver function but did not prevent developmental delay. Genetic analysis identified 14 novel ASL variants.</p><p><strong>Conclusions: </strong>Our study represents the largest cohort of ASLD patients from China reported to date. Despite active interventions, including liver transplantation, the prognosis remains poor, with a high prevalence of developmental delays. The identification of 14 novel pathogenic variants significantly expands the known mutation spectrum of the ASL gene in this population.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"509"},"PeriodicalIF":3.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroretinal structure changes in infantile nephropathic cystinosis.","authors":"Leonie Franziska Keidel, Neringa Jurkute, Benedikt Schworm, Katharina Hohenfellner, Siegfried Priglinger, Axel Petzold, Claudia Priglinger","doi":"10.1186/s13023-025-04018-2","DOIUrl":"https://doi.org/10.1186/s13023-025-04018-2","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to investigate the neuroretinal structure of patients with the lysosomal storage disease cystinosis.</p><p><strong>Methods: </strong>In this retrospective cross-sectional analysis, optical coherence tomography (OCT) was used to measure the peripapillary retinal nerve fiber layer (pRNFL), the optic disc volumes, the prelaminar depth and the macular ganglion cell layer volumes (mGCL) in patients with genetically confirmed infantile nephropathic cystinosis. The same measurements were repeated in an age -and spherical equivalent (SE) matched, healthy control group.</p><p><strong>Results: </strong>The cystinosis group included 40 patients (40 eyes) with a mean age of 20.6 ± 8.6 years and a SE of 0.47 ± 1.85. The healthy control group consisted of 30 patients (30 eyes) with a mean age of 20.7 ± 12.5 years and a SE of 0.47 ± 1.29. A pronounced deposition of crystals in the optic disc was observed in all cystinosis cases. Cystine crystals follow the nerve fibers in a dense, pearl-string pattern. A significantly thicker pRNFL and a higher rate of positive prelaminar depth was evident in the cystinosis group (839.7 ± 151.0 μm vs. 775.7 ± 79.6 μm, p = 0.004). A significantly smaller mGCL volume was found in the cystinosis group as compared to normal controls (0.25 ± 0.03 mm³ vs. 0.35 ± 0.03 mm³, p = 0.036).</p><p><strong>Conclusions: </strong>Cystinosis leads to pronounced crystal accumulation in the optic disc in early stages of the disease. This accumulation occurs in concomitance with the well-described cystine crystal deposits in the cornea, which have previously been considered the foremost ocular sign of cystinosis. The pearl-string appearance of crystal deposition suggests a primarily glial localization. A significantly thicker pRNFL and a higher rate of positive prelaminar depth was observed in the OCT scans of cystinosis patients, explaining the clinical impression of a crowded optic disc. Additionally, retinal neurodegeneration was significant in patients with cystinosis if compared to healthy controls. The optic disc crowding may result from the dense deposition of cystine crystals in the optic nerve head and the GCL thinning could be due to metabolically induced ganglion cell atrophy. However, the exact reason for these changes remains to be elucidated.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"508"},"PeriodicalIF":3.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing an explainable machine learning model to predict false-negative citrin deficiency cases in newborn screening.","authors":"Peiyao Wang, Haomin Li, Xinjie Yang, Lingwei Hu, Yuhe Chen, Ziyan Cen, Pingping Ge, Qimin He, Benqing Wu, Xinwen Huang","doi":"10.1186/s13023-025-04045-z","DOIUrl":"https://doi.org/10.1186/s13023-025-04045-z","url":null,"abstract":"<p><strong>Background: </strong>Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD) is an autosomal recessive disorder affecting the urea cycle and energy metabolism. Newborn screening (NBS) usually relies on elevated citrulline, but some patients have normal citrulline, resulting in false negatives and delayed diagnosis. This study develops an explainable machine learning (ML) model to predict false-negative NICCD cases during NBS.</p><p><strong>Methods: </strong>Data from 53 false-negative NICCD patients and 212 controls, collected retrospectively between 2011 and 2024, were analyzed. The dataset was split into a training set (70%) and a test set (30%). External validation involved 48 participants from distinct time periods. Key predictors were identified using variable importance in projection (VIP > 1) and Lasso regression. Six ML models were trained for evaluation: Logistic Regression, Random Forest, Light Gradient Boosting Machine, Extreme Gradient Boosting (XGBoost), K-Nearest Neighbor, and Support Vector Machines. Performance was evaluated using the area under the receiver operating characteristic curve (AUC) and F1 score. Shapley Additive exPlanations (SHAP) was applied to determine the importance of features and interpret the models.</p><p><strong>Results: </strong>Birth weight, citrulline, glycine, phenylalanine, ornithine, arginine, proline, succinylacetone, and C10:2 were selected as predictive features. Among the ML models, XGBoost demonstrated the most robust and consistent performance, achieving AUCs of 0.971(95%CI: 0.959-0.979), 0.968, and 0.977, and F1 scores of 0.786(95% CI: 0.744-0.820), 0.828, and 0.833 in the training, test, and external validation sets, respectively. SHAP analysis showed that the most important features are citrulline, glycine, phenylalanine, succinylacetone, birth weight, and ornithine. Feature pairs such as citrulline-phenylalanine, citrulline-glycine, succinylacetone-birth weight, and ornithine-glycine showed varying interactions. SHAP force plots, decision plots, and waterfall plots provided insightful patient-level interpretations. Finally, we built a network calculator for the prediction of false-negative NICCD cases ( https://myapp123.shinyapps.io/my_shiny_app/ ).</p><p><strong>Conclusion: </strong>An interpretable machine learning model utilizing metabolite and demographic data enhances the detection of false-negative NICCD cases, facilitates early identification and intervention, and ultimately improves the overall effectiveness of the newborn screening system.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"507"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Currently managed US prevalence of cutaneous venous malformations (cVMs): a nationally representative, retrospective, real-world, subject-blinded, physician-observational probability study.","authors":"Jack Ray Gallagher, Susan Carroll, Jeffrey Martini, Michael Kelly, Maria Gnarra Buethe","doi":"10.1186/s13023-025-03995-8","DOIUrl":"10.1186/s13023-025-03995-8","url":null,"abstract":"<p><strong>Background: </strong>Cutaneous venous malformations (cVMs) are rare vascular anomalies characterized by progressive vessel ectasia, leading to disfigurement, pain, ulceration, and bleeding. These lesions often evade early detection and are notoriously difficult to treat due to the limited dermal bioavailability of systemic therapies. Unlike deep venous malformations, cVMs present unique management challenges and currently lack FDA-approved treatments. To address the paucity of epidemiologic data, we conducted a nationally representative, blinded, real-world observational probability study to estimate the annual treatment prevalence of cVM in the United States. A geographically representative sample of dermatologists, hematologist-oncologists, pediatricians, radiologists, and vascular surgeons was recruited via blinded invitations. Participants self-reported the number of cVM patients treated in the prior 12 months. Estimates were adjusted for comanagement to calculate the national prevalence of unique patients.</p><p><strong>Results: </strong>Of 691 physicians who accessed the study website, 515 (74.5%) completed the survey; 376 (73.0%) reported managing at least one patient with cutaneous-only or mixed (cutaneous and internal) VMs. The estimated annual prevalence was 194,195 patients (95% CI 188,852-200,228), including 135,687 with cutaneous-only VMs and 58,508 with mixed lesions. This corresponds to a prevalence of 0.06% (US population).</p><p><strong>Conclusions: </strong>While cVM is rare, it affects a substantial number of individuals across age groups in the U.S. These findings underscore the need for improved access to care and the development of targeted therapies for this understudied, debilitating condition.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"504"},"PeriodicalIF":3.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244783","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":"X-linked hypophosphatemia and tumor-induced osteomalacia: a narrative review and expert opinion on the diagnostic and therapeutic challenges in the era of burosumab.","authors":"Maria Luisa Brandi, Cristina Eller Vainicher, Danilo Fintini, Andrea Giusti, Andrea Magnolato, Salvatore Minisola, Sandro Giannini","doi":"10.1186/s13023-025-03952-5","DOIUrl":"10.1186/s13023-025-03952-5","url":null,"abstract":"","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"505"},"PeriodicalIF":3.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244797","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":"Rare case of longevity in Hutchinson-Gilford progeria syndrome and literature review.","authors":"Xiao-Ling Cai, Hang Chen, Xue-Qin Lin, Hong Zhang, Yi-Fei Xiang, Ming-Xiang Wu, Kai-Yang Lin","doi":"10.1186/s13023-025-04022-6","DOIUrl":"10.1186/s13023-025-04022-6","url":null,"abstract":"<p><p>Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant disorder characterised by premature ageing, with an average life expectancy of 14.6 years. We report a case of HGPS associated with a typical C. 1824 C > T (P. Gly608Gly) mutation in the 11th exon of the LMNA gene in a 21-year-old woman. The patient presented with a three-year history of progressive exertional dyspnea that acutely worsened over the five days preceding admission. She had a short stature (weight 13 kg, height 85 cm), typical craniofacial features, and scleroderma-like skin changes. Cardiovascular evaluation showed signs of premature ageing (ejection fraction 30.8%). This patient is the oldest among all reported cases of HGPS associated with typical mutations. We describe rapid progression of HGPS in this patient and recommend that physicians should consider coronary heart disease in the differential diagnosis of chest pain in patients with HGPS, regardless of age.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"506"},"PeriodicalIF":3.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244822","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":"Unraveling the mystery of alien hand syndrome: when your hand has a mind of its own.","authors":"Khaled Moghib, Trisha Shivashankar, Thoria I Essa Ghanm, Mona I Elshamy, Eman G Allam, Salomon Izere, Md Al Hasan Mia, Muhannad Wael Abu Arafeh, Mostafa Meshref","doi":"10.1186/s13023-025-04000-y","DOIUrl":"10.1186/s13023-025-04000-y","url":null,"abstract":"<p><strong>Background: </strong>Alien Hand Syndrome (AHS) is a rare neurological disorder characterized by involuntary, complex movements of a limb, often with a sense of estrangement from the affected hand. Initially described in 1908, AHS has since been associated with various neurological conditions, including strokes, neurodegenerative diseases, tumors, and surgical interventions affecting the corpus callosum and frontal lobes.</p><p><strong>Objective: </strong>This study aims to provide a comprehensive review of etiology, clinical manifestations, neuroanatomical basis, and differential diagnosis of AHS, synthesizing findings from published case reports and literature.</p><p><strong>Methods: </strong>This scoping review followed PRISMA-ScR guidelines to systematically analyze AHS case reports from PubMed (2010-2025). Two independent reviewers screened studies using predefined criteria, extracting demographic, clinical, neuroimaging, and treatment data. Eligible case reports required a confirmed AHS diagnosis with complete clinical and neuroimaging documentation. Data synthesis combined descriptive statistics and qualitative analysis to map AHS characteristics across subtypes.</p><p><strong>Results: </strong>A total of 72 cases were reviewed, with a mean patient age of 59.58 years (SD 18.24), ranging from 9 to 89 years. Males accounted for 48.6% (35 cases), while females represented 51.4% (37 cases). The most frequently implicated brain regions were the corpus callosum, supplementary motor area, and posterior parietal cortex. AHS was commonly associated with stroke, neurodegenerative diseases (e.g., corticobasal syndrome, Creutzfeldt-Jakob disease), and brain tumors. The disorder was categorized into three subtypes, each with distinct clinical presentations and underlying neuropathology. Differential diagnoses included psychiatric disorders, movement disorders, and body schema disturbances.</p><p><strong>Conclusion: </strong>AHS remains a rare and complex neurological disorder with diverse etiologies and clinical manifestations. Accurate diagnosis requires thorough clinical evaluation and neuroimaging to differentiate AHS from psychiatric and other neurological conditions. Further research is needed to elucidate its pathophysiology and develop targeted therapeutic approaches.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"503"},"PeriodicalIF":3.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239308","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":"Perspectives of pediatric patients with inborn errors of metabolism on long-term treatment and metabolic emergency management.","authors":"Tanjana Harings, Thilo Bertsche, Alena Gerlinde Thiele, Wieland Kiess, Astrid Bertsche, Skadi Beblo, Martina Patrizia Neininger","doi":"10.1186/s13023-025-04046-y","DOIUrl":"10.1186/s13023-025-04046-y","url":null,"abstract":"<p><strong>Background: </strong>Long-term treatment and emergency management are essential in most pediatric patients with inborn errors of metabolism (IEM). In routine care, these patients receive age-appropriate education to support adherence and self-management. However, little is known about pediatric patients' perspectives on long-term treatment and emergency management. We explored patients' perspectives to identify individual needs and challenges.</p><p><strong>Methods: </strong>After ethical approval and written informed consent, we conducted semi-structured interviews with 79 patients diagnosed with IEM, aged ≥ 6 years. The interview consisted of two parts: long-term treatment (Part A) and emergency management (Part B).</p><p><strong>Results: </strong>Altogether, 79 patients participated. Part A on long-term treatment was completed by 66 patients. Of those, 70% (46/66) reported regular medication intake. While 67% (44/66) experienced their medication as beneficial, 24% (16/66) were unsure whether their medication was helpful. However, adhering to their prescribed treatment regimen was very important for 74% (49/66), mainly to prevent adverse health outcomes (48%, 32/66). Nearly half of patients (48%, 32/66) reported experiencing burden related to their medication, primarily due to its constant presence in everyday life (26%, 17/66) and unpleasant taste (13%, 9/66). Among 42 patients at risk of metabolic emergencies, 62% (26/42) were aware of the risk and were asked about their emergency management in Part B of the interview. Of those, 54% (14/26) were able to describe symptoms and their actions in response. Overall, patients rated their level of preparedness for emergencies as \"moderate\".</p><p><strong>Conclusion: </strong>Pediatric patients with IEM demonstrated a good understanding of and positive attitude toward their medication. However, despite education as part of routine care, gaps remain in awareness and preparedness regarding metabolic emergencies that require further support for the affected patients.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"502"},"PeriodicalIF":3.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239321","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":"Genetic diagnosis of Jordanian patients with glycogen storage diseases.","authors":"Mohammad Shboul, Mohammed El-Khateeb, Rajaa Fathallah","doi":"10.1186/s13023-025-03982-z","DOIUrl":"10.1186/s13023-025-03982-z","url":null,"abstract":"","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"501"},"PeriodicalIF":3.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225728","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":"Expanding the clinical spectrum of pediatric ataxia-telangiectasia: a case series of novel genetic variants, lupus vulgaris, and hyper-IgM phenotypes.","authors":"Damla Baysal Bakır, Özge Atay, Halime Yağmur, Gizem Kabadayı, Mehmet Kocabey, Suna Asilsoy, Nevin Uzuner","doi":"10.1186/s13023-025-03942-7","DOIUrl":"10.1186/s13023-025-03942-7","url":null,"abstract":"<p><strong>Background: </strong>Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by pathogenic ATM gene variants, characterised by progressive cerebellar ataxia, telangiectasia, immunodeficiency, and cancer predisposition. While its immunological and oncological complications are well-documented, clinical heterogeneity, particularly in cases with elevated IgM, poses diagnostic challenges.</p><p><strong>Methods: </strong>Following written informed consent, we retrospectively analysed four pediatric A-T patients followed in our clinic. Clinical, laboratory, and radiological data were reviewed, including immunoglobulin levels, vaccine antibody responses, lymphocyte subsets, and alpha-fetoprotein (AFP) levels. Diagnosis was established based on clinical and laboratory findings, supported by whole-exome sequencing (WES) and targeted ATM gene sequencing.</p><p><strong>Results: </strong>Our findings further support the association between the hyper-IgM phenotype and increased immune dysfunction in A-T. We report the first globally documented case of lupus vulgaris in an A-T patient and identify a previously unreported ATM variant in our country, expanding the disease spectrum. These findings highlight the need for further research on regional genetic variations and their clinical implications.</p><p><strong>Conclusion: </strong>This study highlights the importance of early diagnosis and genetic testing, particularly in atypical presentations. The recognition of novel infectious and autoimmune associations, along with novel variants, underscores the necessity of comprehensive, multidisciplinary follow-up and regional genetic screening efforts.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"500"},"PeriodicalIF":3.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225683","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}