Orphanet Journal of Rare Diseases最新文献

{"title":"Economic burden of propionic acidemia in the United States: a claims-based study.","authors":"Sue Perera, Geetanjoli Banerjee, Erin E Cook, Fan Mu, Mu Cheng, Adina Zhang, Jessie Jie Lan, Lin Zou, Vanja Sikirica","doi":"10.1186/s13023-025-03836-8","DOIUrl":"10.1186/s13023-025-03836-8","url":null,"abstract":"","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"295"},"PeriodicalIF":3.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275535","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":"Causal relationships between alterations in shear stress-related genes and aneurysmal subarachnoid hemorrhage.","authors":"Xiaoxin Wu, Yuanyuan Dai, Xingyang Niu, Minghao Zhang, Jiaoxing Li, Yi Xie, Wenli Sheng, Fei Ye","doi":"10.1186/s13023-025-03784-3","DOIUrl":"10.1186/s13023-025-03784-3","url":null,"abstract":"<p><strong>Background: </strong>Current management of aneurysmal subarachnoid hemorrhage (aSAH) poses significant challenges, with emerging evidence implicating alterations in shear stress (SS) as critical in disease pathogenesis. However, the causal relationships and underlying molecular mechanisms remain elusive. This study aimed to elucidate the causal association of key SS-related genes with aSAH.</p><p><strong>Methods: </strong>SS-related genes were curated from the GeneCards database and transcriptomic datasets responsive to SS conditions. Expression quantitative trait loci (eQTLs) associated with these genes were identified as instrumental variables. An integrative analysis of genome-wide association study data for aSAH with eQTLs was conducted using bidirectional two-sample Mendelian randomization (MR) to identify SS-related genes causally linked to aSAH. Additionally, expression levels of identified genes were compared between ruptured and unruptured aneurysm walls. Functional assessments of these genes in vascular endothelial cells were also performed.</p><p><strong>Results: </strong>We identified 209 SS-related genes potentially implicated in aSAH pathogenesis. Using 599 eQTLs correlated with these genes as instrumental variables, MR analysis revealed that KCNN4 (OR = 0.83, 95% CI: 0.73-0.94) and UGCG (OR = 1.62, 95% CI: 1.07-2.48) were significantly associated with aSAH. Furthermore, RNA-sequencing data demonstrated elevated expression of KCNN4 and UGCG in ruptured intracranial aneurysms compared to unruptured ones. Functional experiments using siRNA-mediated knockdown in HUVECs showed that siKCNN4 increased cell proliferation and disrupted endothelial barriers, while siUGCG enhanced tube formation ability but reduced migration.</p><p><strong>Conclusions: </strong>Our findings suggest a causal relationship between alterations in SS-related genes and aSAH. Specifically, KCNN4 and UGCG emerge as potential biomarkers critical in the disease progression of aSAH. These insights contribute to a better understanding of the molecular basis of aSAH and may guide future therapeutic strategies targeting SS-related pathways.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"296"},"PeriodicalIF":3.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275533","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":"Patients with suspected pulmonary hypertension based on echocardiography in Behçet's disease: a 5-year follow-up study.","authors":"Mustafa Ekici, Alper Sarı, Berkan Armağan, Erdinç Ünaldı, Büşra Fırlatan, Gözde Sevgi Kart Bayram, Buğu Bulat, Uğur Nadir Karakulak, Levent Kılıç, Barış Kaya, Ömer Karadağ, Ali Akdoğan","doi":"10.1186/s13023-025-03825-x","DOIUrl":"10.1186/s13023-025-03825-x","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the long-term functional and transthoracic echocardiographic (TTE) progression in Behcet's disease (BD) patients with pulmonary hypertension (PH), aiming to address knowledge gaps regarding PH in BD.</p><p><strong>Methods: </strong>This study included 17 BD patients with PH detected by TTE and 6 patients with pulmonary artery involvement but without PH from a previous study at Hacettepe University. PH was defined as an estimated systolic pulmonary artery pressure (sPAP) ≥ 40 mmHg. TTE was conducted by a cardiologist blinded to clinical information, with sPAP calculated using the simplified Bernoulli equation. Right heart catheterization was performed only in two patients who underwent pulmonary endarterectomy operations.</p><p><strong>Results: </strong>All 23 patients were reached by telephone, and 13 of the 17 with PH attended the clinic for reevaluation and a TTE was performed. After 5 years, all patients were alive. Clinical worsening or FC progression was not observed in any patient with PH except the ones with Group IV PH. Pulmonary endarterectomy (PEA) was performed in 2 of the 4 Group IV PH patients during follow-up. Additional Group II PH diagnosed due to mitral valve disease in a patient with Group IV PH. Other than the ones who underwent PEA there were no increase in sPAP of the BD patients with PH. Among patients with PAI but without PH during first evaluation; only one was mildly symptomatic after 5 years who had a normal sPAP.</p><p><strong>Conclusion: </strong>Progressive PH was observed only in Group IV PH patients, while other groups remained generally asymptomatic. Although the number of patients enrolled in this study is limited implementation of TEE to the follow-up of BD patients with PAI for screening and monitoring PH can be beneficial for early diagnosis and defining treatment strategy.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"299"},"PeriodicalIF":3.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275538","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":"Factors associated with psycho-behavioral problems among 100 children with phenylketonuria aged 6-18 years.","authors":"Mei Xue, Ming Shen, Shunan Wang, Bo Pang, Xiaoqian Zhang, Kening Chen, Zhixin Zhang, Wenquan Niu","doi":"10.1186/s13023-025-03824-y","DOIUrl":"10.1186/s13023-025-03824-y","url":null,"abstract":"<p><strong>Background: </strong>Phenylketonuria (PKU) is a rare disease. Children who are diagnosed with PKU often encounter psycho-behavioral difficulties, which can significantly impact quality of life and social integration. The aim of this study was to evaluate the prevalence of psycho-behavioral difficulties and explore potential factors associated with their occurrence in PKU children aged 6-18 years.</p><p><strong>Methods: </strong>From May 2022 to May 2024, 100 children with PKU were recruited using a questionnaire-based survey. Data were analyzed using the STATA (version 18.0) and R programming language (version 4.3.3).</p><p><strong>Results: </strong>25% of children aged 6-18 years with PKU exhibited psycho-behavioral problems. Significant factors associated with psycho-behavioral problems in study children included body mass index (multi-adjusted odds ratio, 95% confidence interval, P: 1.135, 1.010-1.276, 0.033), age (3.169, 1.024-9.804, 0.045), pregnancy order (0.143, 0.033-0.607, 0.008), delivery order (0.041, 0.004-0.373, 0.005), mode of disease diagnosis (5.730, 1.935-16.963, 0.002), and dietary therapy pressure (3.321, 1.083-10.181, 0.036). Based on these significant factors, a nomogram model was constructed with descent prediction capability and accuracy.</p><p><strong>Conclusions: </strong>We identified six factors closely associated with psycho-behavioral problems in PKU children, offering insights into risk profiles underlying these problems and guiding the formulation of effective prevention strategies.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"297"},"PeriodicalIF":3.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Reporting preclinical gene therapy studies in the field of Niemann-Pick type C disease according to the ARRIVE guidelines.","authors":"Charlotte Laurfelt Munch Rasmussen, Annette Burkhart, Torben Moos, Louiza Bohn Thomsen","doi":"10.1186/s13023-025-03826-w","DOIUrl":"10.1186/s13023-025-03826-w","url":null,"abstract":"","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"293"},"PeriodicalIF":3.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266895","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":"Liver transplantation in Wilson disease: a single-center experience.","authors":"Zahra Beyzaei, Kiana Ghatei, Alireza Shamsaeefar, Kurosh Kazemi, Saman Nikeghbalian, Ali Bahador, Masoud Dehghani, Seyed-Ali Malekhosseini, Bita Geramizadeh","doi":"10.1186/s13023-025-03827-9","DOIUrl":"10.1186/s13023-025-03827-9","url":null,"abstract":"<p><strong>Background: </strong>Wilson disease is a complex genetic disorder due to copper accumulation, mainly in the liver and brain. It is associated with severe liver disease, which is effectively cured by liver transplantation (LT). This study aimed to analyze the outcome of Wilson disease after LT from a single center in Iran.</p><p><strong>Methods: </strong>In this study, we analyzed data from Wilson patients and donors who received LT from March 2018 to December 2022 at Shiraz University of Medical Sciences, Shiraz. Long-term follow-up and post-LT outcomes for both deceased donor LT (DDLT) and living donor LT (LDLT) were measured. The Kaplan-Meier survival analysis was used to test the survival.</p><p><strong>Results: </strong>106 recipients with LT (LDLT, n = 22; DDLT, n = 84) were included (mean age of adult and pediatric: 33.1 and 10.8 years respectively; male: 58% and female 42%). The average serum ceruloplasmin and urinary copper levels improved in most patients, with values of 15.6 mg/dL and 32.3 µg per 24 h, respectively. For pediatric patients with Wilson's disease, the survival rates at 6 months, 1 year, and 3 years were 97.0%, 96%, and 94.5%, and in adult patients achieved survival rates of 100%, 100%, and 75% at 6 months, 1 year, and 3 years, respectively.</p><p><strong>Conclusions: </strong>LT is considered as a principal therapeutic option with good long-term results in Wilson patients, even in those presenting with hepatic failure. Neurologic manifestations have been improved post-LT; however, de novo neuropsychiatric symptoms begin in some cases after successful liver transplantation.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"292"},"PeriodicalIF":3.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266896","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":"Comparison of two genetic strategies for diagnostic work-up of hypertrophic cardiomyopathy: impact on the diagnosis of Fabry disease or transthyretin amyloidosis.","authors":"Aurélien Palmyre, Fairouz Koraichi, Flavie Ader, Erwan Donal, Céline Bordet, Pascal de Groote, Laurence Faivre, Patricia Reant, Annick Toutain, Karine Nguyen, Bertrand Isidor, Anne-Claire Brehin, Lise Legrand, Estelle Gandjbakhch, Julie Proukhnitzky, Richard Isnard, Nicolas Mansencal, Jean-François Pruny, Jean-Pierre Rabes, Bruno Francou, Catherine Caillaud, Pascale Richard, Philippe Charron","doi":"10.1186/s13023-025-03815-z","DOIUrl":"10.1186/s13023-025-03815-z","url":null,"abstract":"<p><strong>Background: </strong>Diagnostic work-up of patients with hypertrophic cardiomyopathy is crucial for appropriate management. However, the optimal genetic strategy remains debatable. We compared two strategies: targeted testing based on careful examination of clinical red flags versus large multigene panel analysis without gene prioritization. We applied the strategy to the diagnosis of Fabry disease or Hereditary Transthyretin Amyloidosis (GLA or TTR genes respectively).</p><p><strong>Results: </strong>We studied 341 hypertrophic cardiomyopathy index patients. Patients of subgroup 1 (n = 42) had careful clinical analysis and high suspicion of Hereditary Transthyretin Amyloidosis or Fabry disease. They underwent targeted Sanger sequencing. Patients in subgroup 2 (n = 299) did not have clinical selection, and underwent next-generation sequencing analysis of 107 cardiac genes. The yield of genetic testing for pathogenic/likely pathogenic variants in GLA and/or TTR was 28.6% in subgroup 1 (12/42: 5 TTR and 7 GLA) versus 1.0% in subgroup 2 (3/299: 1 TTR and 2 GLA), p < 0.01. Genetic results were obtained after a median of 26.0 days [IQR = 18-59.8] in subgroup 1 versus 193.5 days [IQR = 174-218] in subgroup 2, p < 0.01. Finally, genetic testing cost was 615.60€ or 769.50€ for TTR or GLA targeted analysis respectively, versus 1503.90€ for multigene panel analysis.</p><p><strong>Conclusions: </strong>Both molecular strategies in hypertrophic cardiomyopathy patients are useful for the identification of pathogenic/likely pathogenic variants in TTR/GLA genes. However, targeted genetic testing based on clinical red flags identified causal mutations more efficiently, faster and at a lower cost. Careful clinical analysis is therefore important in guiding molecular strategy and may reduce diagnostic wandering and accelerate delivery of appropriate therapy.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"294"},"PeriodicalIF":3.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266894","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":"Transplacental sirolimus: a new treatment strategy for life-threatening fetal cardiac rhabdomyomas-a case report.","authors":"Kaname Uno, Yoji Nomura, Masahiro Kawaguchi, Anna Ebina, Rina Imanishi, Satoru Kawai, Hiromi Hayakawa","doi":"10.1186/s13023-025-03780-7","DOIUrl":"10.1186/s13023-025-03780-7","url":null,"abstract":"<p><p>Large cardiac rhabdomyomas can disturb hemodynamic flow. Tuberous sclerosis complex is the most common cause of cardiac rhabdomyoma in fetuses. Recently, a mammalian target of rapamycin (mTOR) inhibitor effectively treated rhabdomyomas associated with tuberous sclerosis. Here, we report the effectiveness of an mTOR inhibitor in treating a fetus with large rhabdomyomas exhibiting severe heart failure when administered transplacentally. A 30-year-old pregnant woman was transferred to our hospital due to the presence of a cardiac tumor in the left ventricle (LV) of the fetus, which gradually enlarged to > 40 mm in diameter. The diastolic and systolic functions of the LV were completely disrupted. At 32 weeks of gestation, the fetus showed severe heart failure (cardiovascular profile score 7), with a high risk of death. The hemodynamic flow was consistent with hypoplastic left heart syndrome. Fetal magnetic resonance imaging revealed several cranial regions with 7.9 × 6.9 mm subependymal giant cell astrocytoma (SEGA). The fetus was clinically diagnosed with tuberous sclerosis, and therapy was initiated with maternally administered sirolimus, an mTOR inhibitor. Sirolimus effectively reduced the size of the tumor and improved the hemodynamics of the fetus. No severe complications occurred in the mother or fetus. The baby was born at 39 weeks of gestation with a mildly reduced LV ejection fraction. In addition, the dimensions of the intracranial SEGA decreased somewhat following initiation of maternal sirolimus treatment. Postnatal genetic testing confirmed a mutation in the TSC2 gene. Currently, the baby is 3 months old with normal neurological development. Transplacental sirolimus administration can be a useful in treating large rhabdomyomas that disturb fetal hemodynamics.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"291"},"PeriodicalIF":3.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258664","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":"Patient and caregiver experiences with a patient-support program for setmelanotide treatment of patients with Bardet-Biedl syndrome.","authors":"Ilja Finkelberg, Ioanna M Polichronidou, Tom Hühne, Pia Brensing, Sinem Karaterzi, Johannes Jaegers, Anja Gäckler, Lars Pape, Metin Cetiner","doi":"10.1186/s13023-025-03835-9","DOIUrl":"10.1186/s13023-025-03835-9","url":null,"abstract":"<p><strong>Background: </strong>Bardet-Biedl syndrome (BBS) is a rare genetic disease caused by impaired cilium function and characterized by a plethora of symptoms, including hyperphagia and early-onset obesity, that negatively affect patient and caregiver quality of life. Here, we assessed real-world patient expectations and experiences before and during treatment with setmelanotide, a melanocortin-4 receptor agonist shown to reduce hunger and body weight in patients with BBS.</p><p><strong>Methods: </strong>An online survey was conducted to capture the real-world experience of patients with BBS and their caregivers regarding setmelanotide treatment and the use of a specialist nurse support service aimed at educating patients and their caregivers, and enabling them to administer injections independently. The survey was administered between January 2024 and May 2024 to participants who began treatment between June 2023 and December 2023 at a single center in Germany.</p><p><strong>Results: </strong>Of the 35 respondents, 10 were pediatric patients, 13 were adult patients, and 12 were caregivers. Prior to treatment, the most commonly reported symptoms by pediatric patients and caregivers were insatiable hunger (80% and 83%, respectively) and obesity (50% and 92%, respectively); for adult patients, key symptoms were vision loss (92%) and obesity (69%). Setmelanotide reduced feelings of insatiable hunger and had a positive effect on body weight: ≥ 92% of respondents across survey groups reported feeling less hunger, feeling satiated after meals, and a stable body weight or weight loss (mean BMI z-score ± SD at start: 3.12 ± 0.89, change after 6 months: -0.47 ± 0.37). Improvements in mobility, mood, and behavior were also reported. The specialist nurse support service was rated excellent by all respondents. The personalized approach contributed to high patient and caregiver satisfaction, enabled most of them to administer the drug independently, and ensured high treatment adherence, without any patients discontinuing setmelanotide treatment.</p><p><strong>Conclusion: </strong>Based on this real-world survey of patients with BBS and their caregivers, setmelanotide improved key symptoms related to insatiable hunger and obesity. Personalized multidimensional nursing support at the start of treatment can help address unmet support needs in BBS and may contribute to high rates of treatment satisfaction and adherence.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"290"},"PeriodicalIF":3.4,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248978","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":"Predictive value of liver enzymes in long-term prognosis of hepatic Wilson disease: results from the Wilson AEEH registry.","authors":"Marina Berenguer, Luis García-Villarreal, Antonio Olveira, Esther Mollina Pérez, José María Moreno Planas, Marta Romero-Gutiérrez, José María Pinazo Bandera, Helena Masnou Ridaura, Paula Iruzubieta, María Luisa González Diéguez, Javier Ampuero, José Ramón Fernández Ramos, Carolina Muñoz, Ana Arencibia Almeida, Sara Lorente, Manuel Delgado Blanco, Diego Burgos Santamaría, Mònica Pons Delgado, Alba Cachero, Manuel Hernández Guerra, Judith Gómez Camarero, Sergio Gil Rojas, María Lázaro Ríos, Isabel Carmona Soria, Gemma Carrión, Ariadna Bono, Anna Miralpeix, Pablo Alonso Castellano, Zoe Mariño","doi":"10.1186/s13023-025-03821-1","DOIUrl":"10.1186/s13023-025-03821-1","url":null,"abstract":"<p><strong>Background and aims: </strong>Monitoring Wilson disease (WD) is challenging due to its variable presentation and the absence of reliable biomarkers. This study aims to assess the predictive value of liver enzymes, particularly transaminases, on long-term outcomes in patients with hepatic WD using data from the Spanish Wilson Registry.</p><p><strong>Patients and methods: </strong>We analysed data from 162 WD patients with hepatic involvement and over one year of follow-up. Patients were classified as mild (no cirrhosis) or severe (with cirrhosis) at diagnosis. An \"unstable pattern of transaminases\" was defined as recurrent AST or ALT elevations. Unfavourable outcomes included new cirrhosis, elastography progression > 2 Kpa, liver transplant, or liver-related deaths. Logistic regression models were used to evaluate the impact of various factors on disease outcome.</p><p><strong>Results: </strong>Of 162 patients, 81.5% had mild disease at diagnosis. Most received chelators as first-line therapy, achieving an 81.4% one-year biochemical response. After a median follow-up of 17 years, 59% exhibited an unstable transaminase pattern, and 29% had an unfavourable outcome. Key factors associated with poor outcome included older age at diagnosis (OR = 1.03), lack of early biochemical response (OR = 0.19), advanced disease markers (platelet count, albumin), and an unstable transaminase pattern (OR = 2.92). Transaminase levels did not predict outcomes based on initial disease severity. Even patients with mild disease at diagnosis and persistently normal transaminases could experience progression over time, underscoring the need for more thorough follow-up evaluations.</p><p><strong>Conclusion: </strong>While transaminases are valuable for monitoring WD, they should be used alongside other biomarkers to better predict disease progression.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"288"},"PeriodicalIF":3.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248979","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}