Orphanet Journal of Rare Diseases最新文献

{"title":"Caregivers' experiences and challenges of the diagnostic odyssey in Dravet syndrome.","authors":"Jan Domaradzki, Dariusz Walkowiak","doi":"10.1186/s13023-025-03772-7","DOIUrl":"https://doi.org/10.1186/s13023-025-03772-7","url":null,"abstract":"<p><strong>Background: </strong>Although the genetic background of Dravet syndrome (DS) has been determined and is clearly described, and genetics tests that support a clinical diagnosis are available, DS diagnosis is often based on the clinical assessment alone, which may lead to a late or missed diagnosis. This study explores experiences of caregivers' of persons with DS with the diagnostic odyssey and their perception of its consequences for DS patients.</p><p><strong>Results: </strong>106 family caregivers connected with the Association for People with Severe Refractory Epilepsy DRAVET.PL completed an anonymised, self-administered, computer-assisted online survey on parents' experiences of the diagnostic journey conducted from March to June 2024. Although 96.2% of DS parents reported that their children experienced initial symptoms in the first year of life, 58.4% indicated that it took more than a year before DS was diagnosed and 72.7% reported that their DS child received at least one misdiagnosis. While 6.6% of patients were diagnosed by the first doctor consulted, 65.1% had to consult between two and four specialists and 22.8% consulted more than five specialists. 19.8% of parents confirmed that they sought diagnosis abroad. 58.4% of DS parents suggested that delayed diagnosis was harmful to their children's health. Many believed that it resulted in taking unnecessary or inappropriate medications (67%), hospitalisations (32.1%), or medical interventions (15.1%). Many parents reported problems with accessing genetic counselling and psychological support.</p><p><strong>Conclusions: </strong>Since DS parents report the multifaceted and protracted diagnostic journey in their children, underscoring the duration of the diagnostic process, numerous misdiagnoses and the number of healthcare professionals involved in achieving the confirmed DS diagnosis, this study highlights the need for widespread access to genetic testing, which usually concludes the diagnostic odyssey and is crucial for managing the proper treatment plan for DS patients. It also shows the need to increase general practitioners' awareness of the developmental and epileptic encephalopathy (DEE) and the creation of more rapid and transparent referral procedures for children with DEE.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"234"},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086308","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":"European Reference Network (ERN) ReCONNET methodology for the cross-cultural adaptation of instruments for research and care in the context of rare connective tissue diseases (CROSSADAPT).","authors":"Laurent Arnaud, Oliver Sander, Simona Rednic, Philippe Mertz, Raquel Faria, Francesca Crisafulli, Sofia Silva-Ribeiro, Lou Kawka, Cedric Sztejkowski, Christina Düsing, Thomas Rose, Antonio Lamas, Carlos Vasconcelos, Giulia Fontana, Paolo Semeraro, Teodora Neagu, Mihaela Resteu, Laura Damian, Cristina Pamfil, Camelia Bucsa, Lisa J Matthews, Rosaria Talarico, Marta Mosca, Giuseppe Turchetti, Thomas Thibault, Hervé Devilliers","doi":"10.1186/s13023-025-03674-8","DOIUrl":"10.1186/s13023-025-03674-8","url":null,"abstract":"<p><p>The traditional process of intercultural adaptation, while suitable for one or a few target languages, is not optimal for developing instruments for rare connective tissue diseases (CTDs) in multiple languages simultaneously. The European Reference Network ReCONNET presents the protocol for a novel methodology for cross-cultural adaptation of instruments for research and care in the context of rare CTDs (ReCONNET-CROSSADAPT). It is initiated by the identification of 'key-terms' that are crucial for maintaining the original meaning of the source document. Each language group, led by a senior member and two collaborators, independently assesses the existence and equivalence of these key terms in target languages. Reconciliation meetings are held to establish agreed-upon terms for consistent usage across translations when difficulties arise with key-terms. Subsequently, each language group translates the source document, followed by a reconciliation meeting involving one CTD patient in each group. The purpose of this meeting is to address potential discrepancies among translations, ensuring a comprehensive assessment from a linguistic, cultural and patient perspective. Collective feedback and consensus-based decision-making guide the resolution process. This methodology eliminates the need for backward translation, optimizing time and cost utilization. This new ReCONNET-CROSSADAPT methodology ensures linguistic accuracy, cultural relevance, and contextual appropriateness for the cross-cultural adaptation of instruments for research and care in the context of rare CTDs.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"230"},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079371","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":"TREAT: systematic and inclusive selection process of genes for genomic newborn screening as part of the Screen4Care project.","authors":"Christina Saier, Stefaan Sansen, Joanne Berghout, Kathrin Freyler, Moshe Einhorn, Yaron Einhorn, Leslie Matalonga, Sergi Beltran, Antonio Novelli, Rita Selvatici, Fernanda Fortunato, Silvia Montanari, Maria Martinez-Fresno, Gulcin Gumus, Emanuele Agolini, Nicolas Garnier, Alessandra Ferlini, Enrico Bertini, Janbernd Kirschner","doi":"10.1186/s13023-025-03692-6","DOIUrl":"10.1186/s13023-025-03692-6","url":null,"abstract":"<p><strong>Background: </strong>Genomic newborn screening (gNBS) offers the potential to detect genetic conditions early, enhancing outcomes through timely treatment. It can serve as an additional tool to identify conditions that are not detectable via metabolic screening. The Screen4Care project seeks to develop a systematic approach for selecting treatable rare diseases (RDs) for inclusion in gNBS through the creation of the TREAT-panel.</p><p><strong>Methods: </strong>A set of six selection criteria containing treatability, clinical validity, age of onset, disease severity, penetrance, and genetic feasibility was applied to a comprehensive list of gene-disease pairs. Genes meeting a defined threshold score were included in the TREAT-panel. This automated scoring process was complemented by expert review from clinicians and patient representatives to ensure clinical relevance and adherence to current medical guidelines.</p><p><strong>Results: </strong>The initial gene list, derived from multiple data sources, included 484 gene-disease pairs. After applying the scoring system and two rounds of expert curation, a final list of 245 genes was selected. These genes predominantly represent disorders in metabolic, neurological, and immunological categories, with treatability and early disease onset as key inclusion factors.</p><p><strong>Conclusion: </strong>The Screen4Care TREAT-panel provides a curated, scientifically robust gene set for gNBS, focusing on treatable RDs with early onset and clinical actionability. The panel will be tested in a European pilot project involving approximately 20,000 newborns, contributing to the growing body of evidence for the implementation of next-generation sequencing (NGS) in newborn screening programs.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"231"},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079374","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":"Management of sleep-disordered breathing in achondroplasia: guiding principles of the European Achondroplasia Forum.","authors":"Brigitte Fauroux, Moeenaldeen AlSayed, Tawfeg Ben-Omran, Silvio Boero, Mieke Boon, Valérie Cormier-Daire, Svein Fredwall, Encarna Guillen-Navarro, Melita Irving, Philip Kunkel, Núria Madureira, Mohamad Maghnie, Josef Milerad, Klaus Mohnike, Geert Mortier, Lino Nobili, Zagorka Pejin, Marco Sessa, Sérgio B Sousa","doi":"10.1186/s13023-025-03717-0","DOIUrl":"10.1186/s13023-025-03717-0","url":null,"abstract":"<p><p>Due to the craniofacial anatomy of people with achondroplasia, sleep-disordered breathing (SDB) occurs more frequently than in the average stature population. SDB, which comprises obstructive sleep apnoea (OSA), more rarely central sleep apnoea (CSA), and nocturnal alveolar hypoventilation (NH), may present at any age in patients with achondroplasia. Untreated SDB is associated with neurocognitive dysfunction, cardiovascular, and metabolic complications in children and adults. There continues to be debate on the optimal assessment and management of SDB in achondroplasia. To help address this, the European Achondroplasia Forum (EAF), a network of clinicians and patient advocates representative of the achondroplasia clinical community, organised a virtual workshop in October 2023 to scrutinise, vote and agree upon five guiding principles for managing SDB in achondroplasia. This workshop was attended by 40 healthcare professionals, including clinical geneticists, general practitioners and consultants, orthodontic and orthopaedic surgeons, paediatricians, paediatric endocrinologists and pulmonologists, sleep researchers and specialists, and two patient advocacy group representatives. The five guiding principles focus on lifelong assessment and proactive management, incorporating individualised sleep studies, screening, and a stepwise approach to therapeutic management. The EAF was in favour of all guiding principles, with all achieving 100% consensus with high levels of agreement (range 8.9-9.7/10). In developing guiding principles for the management of SDB in achondroplasia, the EAF aims to facilitate optimal screening and management of SDB in infants, young children, and adults with achondroplasia.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"233"},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aspiration, respiratory complications, and associated healthcare resource utilization among individuals with Rett syndrome.","authors":"Nazia Rashid, Jonathan D Darer, Charles Ruetsch, Xiaoyun Yang","doi":"10.1186/s13023-025-03757-6","DOIUrl":"10.1186/s13023-025-03757-6","url":null,"abstract":"<p><strong>Background: </strong>Individuals with Rett syndrome (RTT) are at high risk for aspiration and also experience high rates of lower respiratory tract infections (LRTI) and respiratory failure (RF).</p><p><strong>Methods: </strong>A retrospective comparative cohort analysis was performed among 89 individuals with RTT with and without evidence of aspiration, using EHR structured and abstracted clinical notes data. Individuals with known or suspected aspiration (per clinical documentation) (cases) were compared to controls on aspiration risk factors, RF, LRTI, and hospitalization.</p><p><strong>Results: </strong>Of eligible individuals, 25 (28.1%) were aspiration cases. The cumulative rate of RF among RTT individuals with and without aspiration was 60.0% and 6.3%, respectively. Aspiration cases were more likely to have risk factors compared to controls during the 6-month baseline including epilepsy (54.5% vs. 4.5%), dysphagia (40.9% vs. 0%), GERD (31.8% vs. 0.0%), scoliosis (31.8% vs. 4.5%), and vomiting (18.2% vs. 0.0%). Aspiration cases were more likely to have LRTI (50% vs. 5.0%) and ≥ 1 inpatient admissions than non-aspiration controls (75.0% vs. 35.0%) (all p < 0.05).</p><p><strong>Conclusions: </strong>Individuals with RTT with known or suspected aspiration are at increased risk of LRTI, RF, and inpatient admissions. Providers should monitor aspiration and institute preventative measures among individuals with aspiration risk factors even in the absence of aspiration symptoms.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"232"},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079370","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":"Treatment preferences among individuals with primary hyperoxaluria type 1 (PH1): a real-world study.","authors":"David S Goldfarb, Jing Voon Chen, Rebekah Zincavage, Brad Padilla, Matthew Sussman, Sandra Salem, Frank Modersitzki","doi":"10.1186/s13023-025-03738-9","DOIUrl":"https://doi.org/10.1186/s13023-025-03738-9","url":null,"abstract":"<p><strong>Background: </strong>Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder causing excessive oxalate production, damaging kidneys and other organs. Nedosiran, launched in the U.S. for individuals with PH1 (≥ 9 years of age; estimated glomerular filtration rate [eGFR] ≥ 30 mL/min/1.73 m²), can be self- or caregiver-administered at home with fixed-dosing for patients ≥ 12 years of age. This real-world study aimed to understand treatment preferences among individuals with PH1, highlighting challenges in administration of current treatments.</p><p><strong>Methods: </strong>A cross-sectional web-based survey was conducted among U.S.-based adults (aged ≥ 18) diagnosed with PH1. The survey consisted of a 20-25 min questionnaire and was conducted from October to December 2023.</p><p><strong>Results: </strong>The study participants (N = 39) included both male (N = 26) and female (N = 13) adults with PH1. Participants came from a range of community settings, including urban (46%), rural (39%), and suburban (15%); and were full- or part-time workers (56%) or students (41%). Most participants were on lumasiran therapy (95%) for an average of 1 year (range: 0.3-1.8 years). The survey revealed that the commonly reported factors important for treatment selection among participants living with PH1 were frequency of administration, treatment administrator, time required for treatment, and place of administration. The ability to self-administer was ranked as the top choice by most participants. Over half (56%) found quarterly injections easy or very easy. Similarly, 56-59% found home administration, whether self- or healthcare provider (HCP)-administered, easy or very easy. Nearly half (46%) considered injections at medical facilities challenging or very challenging. The majority indicated traveling > 15 min for injections would be burdensome (57%) and arranging appointments problematic (54%). When comparing administration methods, 72% preferred self-injection over HCP-administered injections. Regarding treatment regimens, 57% found it easy or very easy to receive monthly injections initially, before switching to quarterly. Additionally, 64% preferred a medication dosage that is not weight-based. While participants expressed a preference for less frequent treatments, 67% preferred self-injection at home over medical facility injections, and 67% preferred monthly injections at home over quarterly injections at a medical facility.</p><p><strong>Conclusions: </strong>This study shows that patients with PH1 value treatments that are convenient and fit their lifestyle.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"228"},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079386","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 variants of SLC6A4 and risk of coronary artery disease: insights from North Indian population.","authors":"Jyotdeep Kour Raina, Minakashee Sharma, Ravi Sharma, Rohit Bhardwaj, Parvinder Kumar, Santasree Banerjee, Rakesh Kumar Panjaliya","doi":"10.1186/s13023-025-03761-w","DOIUrl":"https://doi.org/10.1186/s13023-025-03761-w","url":null,"abstract":"<p><strong>Background: </strong>The activity of SLC6A4 is influenced by its polymorphisms, including the length variation in serotonin transporter linked promoter region (5-HTTLPR), a single nucleotide polymorphism (rs25531), and variable number of tandem repeats in serotonin transporter intronic enhancer (STin2). These polymorphisms have been implicated in the development of vascular diseases. Our research aimed to determine whether the bi-allelic 5-HTTLPR, tri-allelic 5-HTTLPR (rs25531), and STin2 polymorphisms of SLC6A4 were associated with an increased risk of coronary artery disease (CAD) in the North Indian population of Jammu region in Jammu and Kashmir state of India.</p><p><strong>Methods: </strong>In this study, we performed a large cohort case-control study. Here, we recruited 400 patients clinically diagnosed with CAD, and 400 unrelated healthy individuals with similar sex and age range. We performed Polymerase Chain Reaction (PCR) for genotyping the 5-HTTLPR and STin2 polymorphisms. In addition, PCR- Restriction Fragment Length polymorphism (RFLP) was used to perform restriction fragment length polymorphism for the rs25531. Finally, we performed statistical analysis with the yield data.</p><p><strong>Results: </strong>The L-allele of 5-HTTLPR was significantly associated with CAD susceptibility, with an odd ratio (OR) of 1.39 and a p-value of 0.01. However, no significant association was identified for the tri-allelic 5-HTTLPR (rs25531) and STin2 polymorphism with the susceptibility of CAD. The haplotype combinations associated with CAD outcomes include L-12 and LA-10.</p><p><strong>Conclusions: </strong>Although, majority of the previous studies have evaluated the association of 5-HTTLPR biallelic polymorphism with CAD, our findings suggested that the tri-allelic 5-HTTLPR (rs25531) is a more reliable candidate than the bi-allelic 5-HTTLPR, as studying the bi-allelic version alone may generate association bias. Based on the results of this study, the rs25531 and STin2 polymorphisms indicated that the SLC6A4 gene does not contribute to the development of CAD in the population of the of Jammu region in Jammu and Kashmir state of India.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"229"},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079372","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":"Evidence of the impact of CLN2 and CLN3 Batten disease on families in the United Kingdom.","authors":"Sara E Mole, Paul Gissen, Shannon Nordstrom, Suzanne Wait, Louise Allen, Mathilda Antonini, Liz Brownnutt, Richard Brown, Barbara Cole, Frances Gibbon, Robert H Henderson, Sarah Kenrick, Zlatko Sisic, Bob Thompson, Joanna Nightingale","doi":"10.1186/s13023-025-03747-8","DOIUrl":"10.1186/s13023-025-03747-8","url":null,"abstract":"<p><strong>Background: </strong>Neuronal Ceroid Lipofuscinoses (NCLs), also known as Batten disease, are a group of inherited neurodegenerative disorders that mostly arise in childhood. Each of the NCLs is a genetically distinct disease caused by variants in at least 13 different genes (CLN1-CLN14). NCLs are neurodegenerative, and symptoms can include a combination of childhood dementia, epileptic seizures, motor decline and vision loss, and eventually lead to premature death. There is currently no cure for any subtype of NCL, however, enzyme replacement therapy is available for CLN2 disease, and several treatment strategies are being explored for other NCL subtypes. Early diagnosis and initiation of supportive services (e.g. health, education, social services) are essential to preserve quality of life. Only a few studies have investigated family experiences with NCL, many of which are international in scope.</p><p><strong>Methods: </strong>A mixed-method research study was conducted in the UK to understand family experiences in CLN2 and CLN3 disease. It involved an initial literature review, followed by in-depth qualitative interviews. Interview data were analysed using a thematic analysis. Thirteen families (n = 13) participated in the interviews. This represented 16 parents (11 mothers and 5 fathers) of 18 children (10 diagnosed with CLN3 disease and 8 diagnosed with CLN2 disease). Findings were analysed jointly across CLN2 and CLN3 disease.</p><p><strong>Results: </strong>Six overarching themes emerged from the analysis: difficulty in recognising early symptoms; the shock of a diagnosis; the demands of caring for complex and ever-changing needs; a constant battle to access appropriate and timely support services; the extensive impact on the unaffected sibling; and the all-encompassing impact on the family.</p><p><strong>Conclusions: </strong>This study contributes novel UK specific data on family experiences and unmet needs in CLN2 and CLN3 disease. More needs to be done to ensure NCLs are diagnosed early, and timely local support services are made available to protect quality of life for both the affected children and their families.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"223"},"PeriodicalIF":3.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972372","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":"Odevixibat therapy in progressive familial intrahepatic cholestasis with MYO5B variants: a retrospective case series.","authors":"Bertrand Roquelaure, Marco Sciveres, Tassos Grammatikopoulos, Eberhard Lurz, Folke Freudenberg, Dalila Habes, Lionel Thevathasan, Fatine Elaraki, Emmanuel Gonzales","doi":"10.1186/s13023-025-03728-x","DOIUrl":"10.1186/s13023-025-03728-x","url":null,"abstract":"<p><strong>Background and rationale: </strong>Progressive familial intrahepatic cholestasis (PFIC) associated with myosin 5B deficiency is a rare liver disease characterised by elevated serum bile acids (sBAs) and severe pruritus. The objective of this study was to evaluate treatment with the ileal bile acid transporter inhibitor odevixibat in affected children.</p><p><strong>Methods: </strong>This was a retrospective analysis of five children with a diagnosis of PFIC associated with myosin 5B deficiency and pruritus refractory to treatment with rifampicin and ursodeoxycholic acid, starting odevixibat treatment (37.2-120 µg/kg.day) between 15 months and 10 years of age. Clinical and laboratory data were collected regularly, including liver biochemistry and treatment history. Pruritus and sleep disorders were rated on a four-point Likert scale (absent, mild, moderate or severe).</p><p><strong>Results: </strong>In the year before starting odevixibat, all patients presented with moderate to severe refractory pruritus. Four patients had sleep disturbances. One patient had a history of microvillus inclusion disease and was parenterally fed during his first year of life. In the year prior to initiating odevixibat, sBA levels were > 150 µmol/L and total bilirubin levels were > 25 µmol/L in all patients. Within six months after starting odevixibat, sBA levels normalised to < 10 µmol/L and total bilirubin fell to < 15 µmol/L. Bilirubin and sBA levels remained mostly normal throughout the treatment period (from 22 to 39 months) in four patients. Pruritus and sleep disturbances improved in the first three months and disappeared completely on treatment in four patients. In two patients, compliance and access to treatment were limited, which may explain the fluctuations in treatment response. In one patient, odevixibat treatment was discontinued following an episode of infectious gastroenteritis leading to a rise in sBA and symptom recurrence which did not respond to treatment reinitiation. Digestive tolerability of odevixibat was good; no new or worsening gastrointestinal symptoms were observed in any child.</p><p><strong>Conclusion: </strong>This case series indicates that treatment with odevixibat is effective in children with myosin 5B-related PFIC and encourages further research into the utility of this medication in rare forms of PFIC.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"227"},"PeriodicalIF":3.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033465","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":"Age-related neutrophil activation in Hermansky-Pudlak Syndrome Type-1.","authors":"Lourdes Marinna Caro-Rivera, Sonya Malavez-Cajigas, Mercedes Lacourt-Ventura, Andrea P Rivera-Torres, Dorca E Marcano-Jiménez, Pablo López-Colon, José Muñiz-Hernández, Enid Rivera-Jiménez, Mónica Egozcue-Dionisi, Rosa Román-Carlo, Wilfredo De Jesús-Rojas, Marcos J Ramos-Benítez","doi":"10.1186/s13023-025-03758-5","DOIUrl":"10.1186/s13023-025-03758-5","url":null,"abstract":"<p><p>Hermansky-Pudlak Syndrome (HPS) type 1 (HPS-1) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction, and pulmonary fibrosis (HPS-PF), the leading cause of mortality in these patients. HPS-PF manifests earlier than idiopathic pulmonary fibrosis, typically between 30 and 40 years of age. The etiology and drivers of HPS-PF progression remain poorly understood, and no FDA-approved therapies exist. Neutrophil extracellular traps (NETs) and neutrophil-derived mediators have emerged as key players in fibrosis, promoting lung injury, inflammation, and fibroblast activation. This study evaluates the role of neutrophil activation in age-related changes in patients with HPS-1, focusing on differences in inflammatory markers, neutrophil granules, and NETosis capacity. We observed significantly elevated levels of NETs, neutrophil granule proteins (NE, NGAL, LF), and inflammatory cytokines (IL-8, IL-6) in patients with HPS-1 older than 40 years compared to younger patients and healthy controls. Additionally, fibrosis-related markers (MMP-7 and MMP-8) were significantly higher in older patients. Elevated levels of anandamide (AEA), a circulating marker of HPS-PF, were positively associated with neutrophil granule markers in older patients, suggesting its association with fibrosis. Neutrophils from older patients also demonstrated increased NETosis capacity. These findings suggest that age-related neutrophil activation may contribute to an inflammatory environment that promotes fibrosis progression in HPS-1.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"226"},"PeriodicalIF":3.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008673","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}