Orphanet Journal of Rare Diseases最新文献

{"title":"Assessment of cardiometabolic risk using single point insulin sensitivity estimator (SPISE) in pediatric Bardet-Biedl Syndrome: a pilot study.","authors":"Tugce Kandemir, Melek Yildiz, Ummahan Tercan, Ozge Bayrak Demirel, Hasan Yanik, Volkan Karaman, Ayca Dilruba Aslanger, Aslı Derya Kardelen, Sukran Poyrazoglu, Feyza Darendeliler, Guven Toksoy, Firdevs Bas","doi":"10.1186/s13023-026-04353-y","DOIUrl":"10.1186/s13023-026-04353-y","url":null,"abstract":"<p><strong>Background: </strong>Bardet-Biedl syndrome (BBS) carries early cardiometabolic risk, yet pediatric screening is complicated by growth and puberty. The metabolic syndrome (MetS) z-score provides a continuous benchmark for clustered risk. The single-point insulin sensitivity estimator (SPISE), based on body mass index (BMI) and fasting lipids, may offer a practical alternative where insulin testing is impractical. We aimed to assess the association between SPISE and cardiometabolic burden in children with molecularly confirmed BBS, and to compare its ability to identify MetS against the MetS z-score benchmark and insulin-derived indices.</p><p><strong>Methods: </strong>Single-center retrospective pilot study including children/adolescents with genetically confirmed BBS who underwent standardized anthropometry and metabolic profiling (fasting lipids, glucose, insulin; OGTT when available). SPISE-MetS z-score associations were examined using Spearman and adjusted analyses. In adolescents (≥ 10 years), MetS discrimination was evaluated with ROC curves for SPISE, TG/HDL, and homeostatic model assessment for insulin resistance (HOMA-IR), with pairwise DeLong comparisons and Youden-optimal thresholds.</p><p><strong>Results: </strong>Fourteen participants (7 females, 7 males) were evaluated. Median age at last visit was 11.7 years [IQR 7.6-15.5]; BMI SDS was 3.05 [2.47-3.57]. The median MetS z-score was 1.60 [0.90-1.75]. SPISE correlated inversely with the MetS z-score (ρ=-0.57, p = 0.021), and adjusted models (age, sex, BMI-SDS) retained significance. Among adolescents (n = 10), SPISE showed the highest AUC for MetS (AUC 0.95; 95% CI 0.82-1.00) versus TG/HDL (AUC 0.81) and HOMA-IR (AUC 0.60); pairwise differences were not statistically significant. Youden-optimal SPISE ≤ 3.34 identified MetS with high sensitivity in adolescents. Confidence intervals were wide, reflecting the small sample size.</p><p><strong>Conclusions: </strong>In this single-center pediatric BBS cohort, SPISE tracked continuous MetS burden and showed numerically stronger discrimination for MetS than insulin-derived indices. These findings highlight the potential utility of SPISE as a feasible tool for cardiometabolic monitoring in syndromic obesity, where laboratory access may be limited. Beyond BBS, SPISE may support early risk stratification and follow-up in rare obesity models of metabolic risk, but multicenter prospective validation remains warranted.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13445732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679286","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":"Real world experience of carglumic acid for methylmalonic and propionic acidurias: the second interim analysis of the multicentre observational PROTECT study.","authors":"Sufin Yap, Elena Procopio, Alessandro Rossi, Alberto Burlina, Lucy Dougherty-de Miguel, Elvira Cañedo, Francesca Furlan, Sinziana Stanescu, Thibault Delcroix, Zahir Boutoub, Vincenzo Giordano","doi":"10.1186/s13023-026-04522-z","DOIUrl":"10.1186/s13023-026-04522-z","url":null,"abstract":"<p><strong>Introduction: </strong>Propionic aciduria (PA) and methylmalonic aciduria (MMA) are rare inherited metabolic disorders marked by recurrent metabolic decompensation and hyperammonaemia, resulting in neurological morbidity, chronic complications, and substantial healthcare burden. Although carglumic acid (Carbaglu®) is established for acute hyperammonaemic crises, evidence for its long-term use is limited. This study reports the 18-month interim analysis of PROTECT, a large prospective observational study evaluating chronic Carbaglu® therapy in PA and MMA.</p><p><strong>Methods: </strong>PROTECT is a prospective, longitudinal, observational study conducted across 34 centres in seven European countries. Patients with PA or MMA receiving long-term Carbaglu® for at least six months were eligible. Clinical data were extracted from medical records and analysed descriptively. Annualised pre- and post-treatment comparisons were performed in patients with at least six months of life without long-term Carbaglu® prior to initiation. Outcomes included metabolic decompensation events, ammonia control, healthcare utilisation, and growth parameters.</p><p><strong>Results: </strong>Fifty-eight patients were included in this interim analysis. Among 39 evaluable patients, long-term Carbaglu® treatment was associated with reduced annualised metabolic decompensation events, including hyperammonaemic episodes. Mean peak ammonia levels during decompensations and background ammonia concentrations were significantly lower following treatment initiation. Healthcare utilisation decreased substantially, with significant reductions in inpatient admissions, inpatient days, and emergency room visits. Growth parameters remained stable in patients initiating treatment later in life, while patients treated from birth demonstrated sustained metabolic stability and favourable growth profiles.</p><p><strong>Discussion: </strong>Despite heterogeneity and limitations inherent to real-world observational data, these findings indicate clinically meaningful improvements in metabolic control and healthcare burden with long-term Carbaglu® therapy. Reductions in both acute and background ammonia exposure suggest potential cumulative neuroprotective benefits.</p><p><strong>Conclusions: </strong>This 18-month interim analysis supports Carbaglu® as a beneficial long-term treatment option for patients with PA and MMA, with particular promise when initiated early in life. Ongoing follow-up will further clarify long-term outcomes and inform optimisation of chronic management strategies.</p><p><strong>Clinical trial statement: </strong>Findings based on clinical trial NCT04176523 titled the PRospective Observational study of long-TErm Carbaglu® for the Treatment of PA & MMA (PROTECT), registered retrospectively at ClinicalTrials.gov on 25th November 2019, available at https://clinicaltrials.gov/study/NCT04176523.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113135","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: Randomized investigation to evaluate phenylalanine fluctuation after overnight fasting in PKU patients treated with prolonged-release versus standard amino acid protein substitute.","authors":"Anne Daly, Fatma Ilgaz, Sharon Evans, Catherine Ashmore, Alex Pinto, Anita MacDonald","doi":"10.1186/s13023-026-04386-3","DOIUrl":"10.1186/s13023-026-04386-3","url":null,"abstract":"","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649136","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 patients with rare diseases in the Middle East: challenges & opportunities - insights from the Rare Advocacy Council.","authors":"Agnès Farrugia, Ahmed Bahey, Ahmad Tarawah, Arwa Al Yamani, Carla Abou Selwan, Dania Mohty, Denis Wolfs, Dorica Dan, Hafiz Mosa Ali Malhan, Johan De Graaf, Stefan Živković, Yasser Wali, Youmna Ouraybi, Zakareya Al Kadhem, Nafisa Tawfiq, Lee Davelaar, Noha Mohamed Mahmoud Abdelbaky","doi":"10.1186/s13023-026-04469-1","DOIUrl":"10.1186/s13023-026-04469-1","url":null,"abstract":"<p><strong>Background: </strong>Rare diseases affect a small percentage of the population but collectively impact millions worldwide. In the Middle East, the challenges are intensified by regional factors such as high rates of consanguinity, sociocultural stigma, limited diagnostic capacity, and inadequate healthcare infrastructure. These challenges often lead to delayed diagnoses, restricted access to treatment, and poor quality of life for affected individuals and their families.</p><p><strong>Methods: </strong>The Rare Advocacy Council conducted two 1.5-hour virtual expert panels involving 14 regional and international stakeholders (5 clinicians, 4 patient advocates, and 5 international academic experts) to identify and prioritize the challenges of managing rare diseases in the Middle East region. Discussions were organized across four domains: disease recognition and diagnosis, the patient journey and continuum of care, access to timely diagnostics, and access to adequate treatment, followed by structured online voting (involving only clinicians and patient advocates; n = 9), discussions focused on prioritization, and a descriptive follow-up survey to identify the most critical barriers and propose actionable solutions.</p><p><strong>Results: </strong>Key challenges identified included the lack of national disease registries, limited public awareness, underrepresentation of patient voices in decision-making, fragmented multidisciplinary care, and restricted access to diagnostics and advanced therapies. Top priorities included developing national registries, enhancing media-driven education, strengthening collaboration among care providers, and improving treatment accessibility through policy reforms.</p><p><strong>Conclusions: </strong>Effective management of rare diseases in the Middle East requires a coordinated, patient-centered approach. Strengthening health system infrastructure, investing in education, and aligning policy with patient needs are essential for sustainable improvement. Collaborative action among policymakers, healthcare providers, and advocacy groups can significantly advance care delivery and improve outcomes for individuals living with rare diseases.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649216","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":"Abstracts of the ERICA ERN research conference.","authors":"","doi":"10.1186/s13023-026-04450-y","DOIUrl":"10.1186/s13023-026-04450-y","url":null,"abstract":"","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 Suppl 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605110","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":"Defining the therapeutic corridor of stability in enzyme replacement therapy for Pompe disease: a position statement.","authors":"Benedikt Schoser","doi":"10.1186/s13023-026-04518-9","DOIUrl":"10.1186/s13023-026-04518-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Pompe disease, also known as glycogen storage disease type II, is a rare, progressive lysosomal storage disorder caused by pathogenic variants in the GAA gene. Enzyme replacement therapy has transformed the natural history of the disease; however, with three agents now approved - alglucosidase alfa, avalglucosidase alfa, and cipaglucosidase alfa plus miglustat - clinicians lack a consensus quantitative framework for determining when a patient has left the zone of therapeutic stability and requires treatment reassessment, escalation, or switching.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A structured synthesis was conducted of Phase 2 and Phase 3 randomized controlled trials, open-label extension studies, registry analyses, real-world observational datasets, switching studies, scoping review evidence on global diagnostic and epidemiological variation, and consensus recommendations evaluating approved enzyme replacement therapies for Pompe disease, with an emphasis on late-onset Pompe disease. Outcome domains evaluated included forced vital capacity percentage predicted, six-minute walk test distance, urinary hexose tetrasaccharide, serum creatine kinase, maximal inspiratory and expiratory pressures, anti-drug antibody titers, functional motor scales, and patient-reported outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Across LOTS, COMET and its 97- and 145-week extensions, PROPEL and ATB200-07, ATB200-02, the STIG real-world cohort, the International Pompe Registry, European Pompe Consortium start-switch-stop criteria, post hoc PROPEL switching analyses, real-world alglucosidase-to-avalglucosidase switching data, and the first multicenter real-world analysis of switching to next-generation enzyme replacement therapies, a coherent therapeutic corridor of stability emerges. Forced vital capacity change within approximately - 1% to + 5% per year defines the respiratory stability corridor; a confirmed decline exceeding 5% over 12 months constitutes an alarm threshold. For the six-minute walk test, stabilization within approximately ± 25 m of the peak is an adequate response, whereas a confirmed decline of more than 25 m from the peak is actionable. Biomarker improvement or normalization of urinary hexose tetrasaccharide and creatine kinase is achievable with next-generation enzyme replacement therapies and serves as an early surrogate of enhanced lysosomal glycogen clearance. Multicenter real-world switching data indicate that transitions between enzyme replacement therapy preparations are generally feasible and associated with clinical stability in late-onset Pompe disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This formal, multi-domain therapeutic corridor of stability for enzyme replacement therapy in Pompe disease is grounded in available Phase 2, Phase 3, extension, registry, consensus, and real-world evidence. The framework supports structured monitoring, timely reassessment of treatment, and personalized management for patients r","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649199","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":"Diagnosis of rare diseases based on facial phenotype: a quantitative assessment using 2D and 3D photography in Stickler syndrome.","authors":"Adèle Rohée-Traoré, Maxime Taverne, Quentin Hennocq, Thomas Bongibault, Alejandra Daruich, Dominique Bremond-Gignac, Jean-Daniel Kün-Darbois, Pierre-Raphaël Rothschild, Roman-Hossein Khonsari","doi":"10.1186/s13023-026-04323-4","DOIUrl":"10.1186/s13023-026-04323-4","url":null,"abstract":"<p><p>Stickler syndrome (SS) is a rare genetic disorder caused by mutations in collagen-encoding genes. Patients with SS are at an increased risk of retinal detachment, with ophthalmologic complications often presenting as the first symptom due to significant diagnostic delays. These delays contribute to severe visual impairment, even in early childhood, making diagnostic uncertainty a major clinical challenge. This study assessed the feasibility of early SS detection using facial features. Supervised machine learning models, including XGBoost and support vector machines (SVM), were applied to 2D and 3D facial photographs to differentiate individuals with SS from healthy controls. The models achieved 92% accuracy in identifying SS patients using full-face 2D and 3D photographs. When focusing specifically on the orbitonasal region in 3D images, classification accuracy increased to 96%. Facial morphology in rare diseases such as Stickler syndrome can serve as a highly accurate, non-invasive screening tool. AI-based analysis has the potential to reduce diagnostic delays and prevent associated complications, improving patient outcomes.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes in alpha-mannosidosis: a systematic review of therapeutic approaches.","authors":"Arezki Azzi, Reem Bin Shlhoob, Hassan Al-Shehri","doi":"10.1186/s13023-026-04394-3","DOIUrl":"10.1186/s13023-026-04394-3","url":null,"abstract":"<p><strong>Background: </strong>Alpha mannosidosis (AM) is a rare lysosomal storage disorder caused by a deficiency in the α-mannosidase enzyme, resulting in impaired glycoprotein metabolism within lysosomes. Enzyme dysfunction is attributed to an autosomal recessive mutation in the MAN2B1 gene. Affected individuals present with a broad spectrum of manifestations, including developmental delays, cognitive decline, musculoskeletal abnormalities, hearing difficulties, and recurrent infections. Current therapeutic options are limited to hematopoietic stem cell transplantation and the more recently developed enzyme replacement therapy.</p><p><strong>Objective: </strong>The aim of this review was to evaluate and compare the therapeutic outcomes, benefits and challenges associated with Hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) in the treatment of AM.</p><p><strong>Methods: </strong>A systematic search across PubMed, MEDLINE, EMBASE, the Cochrane Library, OMIM, and ScienceDirect identified 12 original studies from 307 records. The data are presented narratively due to the scarcity of literature and the heterogeneity of study designs and interventions.</p><p><strong>Results: </strong>A total of 28 patients who received hematopoietic stem cell transplantation showed improvements in preserving neurocognitive function and skeletal stabilization and reduced infection rates, especially when performed at relatively young ages. However, this treatment carries significant risks, including infections, graft-versus-host disease, and increased morbidity and mortality, particularly in older patients. Conversely, enzyme replacement therapy was administered to 75 patients, who demonstrated a favorable safety profile, enhanced respiratory function, reduced skeletal abnormalities, and improved overall quality of life. However, enzyme replacement therapy has limited efficacy in preventing neurocognitive decline and requires lifelong administration.</p><p><strong>Conclusion: </strong>Both interventions yield better outcomes when initiated early, particularly before cognitive deterioration becomes significant. This review emphasizes the importance of a timely diagnosis to optimize treatment outcomes and prevent severe complications.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13390369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550050","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":"Launching a multi-level data strategy for rare eye diseases: a methodological case study from national to European scale.","authors":"Camille Beluffi-Marin, Marilyne Oswald, Isabella Anna Vacchi, David Keegan, Bart Peter Leroy, Hélène Dollfus","doi":"10.1186/s13023-026-04505-0","DOIUrl":"https://doi.org/10.1186/s13023-026-04505-0","url":null,"abstract":"<p><p>Rare eye diseases bring unique challenges in clinical research and patient care due to their heterogeneity, low prevalence, and dispersed expertise. To address these challenges, an integrated multilevel data strategy has been developed in France and Europe, enabling structured, interoperable data collection and reuse across national and transnational initiatives. In this paper, we present a methodological framework using the metaphor of a spaceship to illustrate the vertical articulation of this ecosystem, from national infrastructures to European platforms. At the base of the spaceship lies BaMaRa, France's national registry for rare diseases, which ensures the systematic collection of core clinical data at the point of care. The next stage is FREDD, a disease-specific data warehouse dedicated to rare eye conditions, developed by the SENSGENE network thanks to the France 2030 RaReTiA project. FREDD integrates granular phenotypic and genotypic data, allowing for in-depth research and cohort building. FREDD is fully interoperable with BaMaRa, ensuring data consistency and minimizing redundancies. The third level of the spaceship is REDgistry, the European registry for rare eye diseases coordinated by ERN-EYE. REDgistry allows for cross-border data harmonization and aligns with FAIR principles to facilitate data sharing and secondary use in international research. At the top of the structure is the European Health Data Space, a future platform enabling secure and standardized access to health data for research and policy-making at the EU level. At the core of this architecture remains the patient, whose data is the very foundation of the system. Although not always actively involved in data collection, the patient remains central to the purpose and structure of each data layer. Building and sustaining such a complex infrastructure requires the coordination of a wide range of stakeholders, including clinicians, research networks, data stewards, hospital IT departments, national authorities, and European institutions. The success of this multilevel model depends on shared standards, transparent governance, and sustained collaboration across all actors. Together, they form the propulsion system of the spaceship, enabling the structured reuse of high-quality data to accelerate research and improve care in the field of rare eye diseases.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550043","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":"Eating behaviour phenotype in the MYT1L-related neurodevelopmental disorder: a deep phenotyping study using standardized questionnaires.","authors":"Juliette Coursimault, Emilie Guillon, François Lecoquierre, Camille Charbonnier, Anne-Marie Guerrot, Alice Goldenberg, Gaël Nicolas, Elise Schaefer, Anael Ayrolles, Richard Delorme, Florence Riccardi, Maude Grelet, Roseline Caumes, Mathilde Nizon, Bertrand Isidor, Guillaume Jouret, Caroline Rooryck, Jeanne Amiel, Anne-Sophie Alaix, Victor Morel, Adeline Jacquinet, Cyril Mignot, Laurence Faivre, Emilie Fraile-Caietta, Sarah Chalopin, Béatrice Dubern, Christine Poitou","doi":"10.1186/s13023-026-04497-x","DOIUrl":"10.1186/s13023-026-04497-x","url":null,"abstract":"<p><strong>Background: </strong>The MYT1L-related neurodevelopmental disorder (MRND) is associated with global motor and language delay, intellectual disability, behavioural disturbances, epilepsy and frequent early-onset obesity. Eating disturbances have been reported but remain poorly characterized. A systematic characterization of the eating behaviour phenotype is essential to improve diagnosis and management.</p><p><strong>Methods: </strong>We conducted a multicentre study including 21 French-speaking individuals with a molecularly confirmed MRND and either overweight/obesity or eating behaviour disturbances. Eating behaviours were reported by relatives using validated questionnaires widely employed in rare obesity research: the Dykens Hyperphagia Questionnaire (HQ), the Trousseau Impulsivity Questionnaire, the Children's Eating Behaviour Questionnaire (CEBQ), the Food Cravings Questionnaire-Trait-reduced (FCQ-T-r, adults only), and a Visual Analogue Scale (VAS) for hunger. When available, questionnaire results were compared with published studies using the same instruments.</p><p><strong>Results: </strong>Persistent hyperphagic behaviours were identified in the majority of patients, with the HQ questionnaire highlighting sustained food-seeking behaviours and pervasive food preoccupation. The mean global score was 25.9, indicating a moderate yet sustained hyperphagic profile. CEBQ revealed a strong attraction to food combined with reduced satiety responsiveness and rapid eating. Hunger was reported as persistent throughout the day. In children food impulsivity was less frequent (5/14; 36%) and no correlation was found between impulsivity and hyperphagia severity, contrasting with findings in other obesity syndromes. Among adults, 62.5% had scores suggestive of food addiction (FCQ-T-r ≥ 50).</p><p><strong>Conclusion: </strong>This study delineates an eating behaviour profile in a symptom-enriched subgroup of individuals with MRND, characterized by moderate but sustained hyperphagia, persistent hunger, impaired satiety, low food-related impulsivity in children but frequent food craving/addiction in adults. These findings support early, age-adapted and multidisciplinary management strategies and highlight the need for targeted interventions to reduce the burden on affected individuals and families.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550015","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}