Orphanet Journal of Rare Diseases最新文献

{"title":"The new frontier of newborn screening: integrating genomics, metabolomics, and data science for inborn errors of metabolism.","authors":"Muhammad Wasim, Yajun Wang, Guoda Ma","doi":"10.1186/s13023-026-04513-0","DOIUrl":"https://doi.org/10.1186/s13023-026-04513-0","url":null,"abstract":"<p><p>Newborn screening (NBS) for inborn errors of metabolism (IEMs) represents one of the most successful public health initiatives of the past century. Originating with the simple bacterial inhibition assay for phenylketonuria, the field was revolutionized by tandem mass spectrometry (MS/MS). Today, we stand at the precipice of a second, more profound revolution driven by the convergence of high-throughput genomics, next-generation metabolomics, and advanced data science. This review articulates this paradigm shift, detailing how MS/MS is being augmented by targeted DNA analysis and how whole genome sequencing and untargeted metabolomics, integrated with artificial intelligence, are expanding the detectable universe of disorders and enabling precision interventions. However, this powerful multi-omic approach raises critical challenges: incomplete penetrance, overdiagnosis, economic burden, psychosocial impacts, algorithm biases, and the genomic data gap that exacerbates health disparities. We critically examine the practical limitations of AI, the lack of evidence for cost-effectiveness, the slow pace of database updates, and the need for short-term reanalysis systems to \"rescue\" cases left undiagnosed. Global policy variations and data-sharing governance frameworks are also addressed. We conclude that the future of NBS lies not in sequential technology replacement, but in the responsible creation of a sophisticated, multi-omic biomedical information system to transform NBS into a foundational pillar of precision pediatric medicine.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245689","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":"Health and social challenges faced by rare disease patients in Hong Kong: a cross-sectional study.","authors":"Roger Yat-Nork Chung, Alvin Yik-Kiu Hui, Dong Dong, Jonathan Ka-Long Mak, Cheryl Shu Ming Chia","doi":"10.1186/s13023-026-04482-4","DOIUrl":"https://doi.org/10.1186/s13023-026-04482-4","url":null,"abstract":"<p><strong>Background: </strong>Literature suggests that rare disease (RD) have adverse effects on patients' physical and psychosocial well-being. RD patients also face various challenges in their daily lives. This study aims to quantify the impact of RDs on patients in Hong Kong in terms of their sociodemographic characteristics, health-related conditions, patient experience, psychosocial support, illness perception, and self-esteem.</p><p><strong>Methods: </strong>We conducted a cross-sectional survey of RD patients in Hong Kong. A mixed-mode survey approach, which included purposive, opportunity, and snowball sampling, was adopted. Participants were recruited through Rare Disease Hong Kong (RDHK) and completed a face-to-face, interviewer-administered survey(n = 176). The 127-item survey instrument covered aspects on sociodemographic characteristics, health-related conditions, patient experience, psychosocial support, illness perception, and self-esteem. Health-related quality of life (HRQL) was assessed using 12-item Short-Form Health Survey version 2 (SF-12 v2), from which a Physical Component Summary was derived for physical health, and a Mental Component Summary for psychological health. Univariate analyses and multivariate linear regression analyses were conducted subsequently to examine the associations between HRQL and sample characteristics.</p><p><strong>Results: </strong>RD patients in this study were found to have poor physical and psychological HRQL compared with population norms. They also faced challenges and difficulties in their daily lives, including but not limited to economic activities, ability to work, sleep quality, activities of daily living, patient experience, psychosocial support, outlook on life, and self-esteem.</p><p><strong>Conclusions: </strong>To our knowledge, this is the first study in Hong Kong that quantifies the impact of RDs on patients' HRQL, and their experience throughout the disease journey. Due to the multi-faceted impact of RD on their patients, we opine that it is critical to adopt a capability approach that does not merely emphasize on the resourcist right and entitlement of the patients, but also ensures equality in capabilities in converting resources to outcomes they value by focusing on the social determinants of health beyond healthcare policies.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245669","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":"Impact of CFTR modulators on caregiver burden in cystic fibrosis: a cross-sectional study in Brazil.","authors":"Verônica Del Gragnano Stasiak Bednarczuk Oliveira, Vinícius Bednarczuk Oliveira, Marise Basso Amaral, Marilis Dallarmi Miguel","doi":"10.1186/s13023-026-04514-z","DOIUrl":"https://doi.org/10.1186/s13023-026-04514-z","url":null,"abstract":"<p><strong>Objective: </strong>To assess caregiver burden, health-related quality of life, and work productivity among primary caregivers of individuals with cystic fibrosis (CF) in Brazil, comparing caregivers of patients using elexacaftor/tezacaftor/ivacaftor (ETI) with those of non-users, and analyzing differences according to the age group of the care recipient.</p><p><strong>Methods: </strong>This cross-sectional study was conducted between September and November 2025 using an online questionnaire. Eligible participants were primary caregivers of individuals with CF living in Brazil. Collected data included sociodemographics, CFTR modulator use, caregiving time, and out-of-pocket health-related expenses. Validated instruments included the 12-item Zarit Burden Interview (ZBI-12), the EQ-5D-3L (utility index and Visual Analogue Scale), and the Work Productivity and Activity Impairment Questionnaire for Caregivers (WPAI: CG). Descriptive analyses and group comparisons were stratified by ETI use and age group of the care recipient.</p><p><strong>Results: </strong>A total of 174 caregivers from all Brazilian regions participated; 90.2% were mothers, with a median age of 35 years (IQR: 28-45). The individuals receiving care had a median age of 11 years (IQR: 7-14) among modulator users and 3 years (IQR: 1-7) among non-users, and 44.8% used CFTR modulators. Caregivers of non-modulator users dedicated significantly more time to daily caregiving (300 min [IQR: 180-300] vs. 180 min [IQR: 90-240]; p = 0.002) and reported more frequent consultations (p = 0.003). ZBI-12 scores were higher in the no-modulator group (20.0 [IQR: 16.0-25.2] vs. 15.5 [IQR: 11.2-23.0]; p = 0.006), with the greatest difference observed among caregivers of children under 5 years (20.0 vs. 14.0; p = 0.003), a group currently without access to modulators through the public health system. EQ-VAS was lower in the no-modulator group (65.0 [IQR: 50.0-80.0] vs. 70.0 [IQR: 50.0-80.0]; p = 0.041). Absenteeism (15.8% [IQR: 0.0-28.6] vs. 0.0% [IQR: 0.0-16.4]; p = 0.034), presenteeism (50.0% [IQR: 5.0-60.0] vs. 20.0% [IQR: 0.0-50.0]; p = 0.048), and activity impairment (50.0% [IQR: 22.5-70.0] vs. 30.0% [IQR: 0.0-60.0]; p = 0.011) were significantly higher among caregivers without modulator access.</p><p><strong>Conclusion: </strong>Use of CFTR modulators was associated with lower caregiver burden, better health perception, and reduced work productivity loss.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245728","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":"Respiratory microbiome dysbiosis in STAT3 hyper-IgE syndrome (Job syndrome).","authors":"Cristian Roca, Matthew A Greenwald, Bryan T Zorn, Ling Sun, Gang Chen, Alexandra F Freeman, Richard C Boucher, Kenneth N Olivier, Matthew C Wolfgang","doi":"10.1186/s13023-026-04508-x","DOIUrl":"https://doi.org/10.1186/s13023-026-04508-x","url":null,"abstract":"<p><p>STAT3 hyper-IgE syndrome (STAT3-HIES), historically known as Job syndrome, is a rare primary immunodeficiency caused by dominant-negative mutations in STAT3. STAT3-HIES is characterized by impaired mucosal immunity, connective tissue abnormalities, and recurrent cutaneous and pulmonary infections. Although STAT3-dependent immune and epithelial pathways are central to airway host defense, the respiratory microbiome in STAT3-HIES remains poorly defined. To address this question, we profiled upper and lower respiratory tract microbiomes using 16S rDNA gene sequencing of oral rinse samples from eight STAT3-HIES participants and eight matched healthy controls, and bronchoalveolar lavage fluid (BALF) samples from eight STAT3-HIES participants and six healthy controls that passed sequencing quality thresholds. Oral rinse samples from STAT3-HIES participants showed lower phylogenetic diversity and significantly altered microbial community structure compared with controls. In BALF, α-diversity was comparable between groups, but β-diversity differed significantly, indicating altered lower airway microbial community composition in STAT3-HIES. Differential abundance analysis identified enrichment of the genus Rothia in STAT3-HIES BALF, and Rothia relative abundance positively correlated with BALF IL-1β, IL-1RA, and IL-8. Although limited by cohort size, these findings provide the first characterization of respiratory microbiome alterations in STAT3-HIES and suggest that impaired STAT3-dependent immune pathways may influence airway microbial ecology and inflammatory responses.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245739","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":"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685170/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimation of the genetic susceptibility prevalence of primary ciliary dyskinesia via the gnomAD v4.1.0 database.","authors":"Rutao Dai, Ya Dao, Xichen Zhang, Yongyu Ma, Xian Zhu, Yunshan Gao, Jun Wu, Liu Sun","doi":"10.1186/s13023-026-04501-4","DOIUrl":"10.1186/s13023-026-04501-4","url":null,"abstract":"<p><strong>Background: </strong>Primary ciliary dyskinesia (PCD) is a rare genetic disorder that is predominantly inherited in an autosomal recessive pattern and is caused by structural or functional ciliary abnormalities. Previous studies on the genetic susceptibility prevalence of PCD have been largely based on limited populations, and there is a lack of global estimates derived from large-scale population genetic databases. This study estimates the carrier frequency and genetic susceptibility prevalence of PCD via the latest data from the gnomAD v4.1.0 database and compares the results with those of previous studies.</p><p><strong>Methods: </strong>We selected genes related to PCD with \"Definitive\" or \"Strong\" associations as determined by the ClinGen Motile Ciliopathy Gene Curation Expert Panel. According to ACMG/AMP guidelines, variables were classified for pathogenicity, including loss-of-function variants (pLOFs) and pathogenic/likely pathogenic missense variants. Using the allele frequency (AF) of these variants from the Genome Aggregation Database (gnomAD) v4.1.0 (containing data from 807,162 individuals) and applying the Hardy‒Weinberg equilibrium principle, we calculated the global and population-specific genetic susceptibility prevalence and carrier frequency of PCD.</p><p><strong>Results: </strong>Among the 31 PCD-associated genes, 5252 eligible variants were included, comprising 5156 pLOF and 96 P/LP variants. The estimated global genetic susceptibility prevalence of PCD is approximately 1 in 20,103, with a corresponding overall carrier frequency of approximately 1 in 25. The Middle East region has the highest prevalence rate of 1 in 4,744, as well as the highest carrier frequency.</p><p><strong>Conclusion: </strong>The estimated global genetic susceptibility prevalence of primary ciliary dyskinesia is approximately 1 in 20,103, with an overall carrier frequency of 1 in 25, indicating significant heterogeneity among ethnic populations. The global genetic susceptibility prevalence estimate is lower than the previous estimate of 1/7,554.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536533","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":"Sexual and reproductive life in adolescents and young adults with phenylketonuria: a cross-sectional study.","authors":"Bożena Mikołuć, Dariusz Walkowiak, Dorota Korycińska-Chaaban, Łukasz Kałużny, Maria Giżewska, Ewa Starostecka, Agata Lange, Jarosław Walkowiak","doi":"10.1186/s13023-026-04509-w","DOIUrl":"10.1186/s13023-026-04509-w","url":null,"abstract":"<p><strong>Background: </strong>Phenylketonuria (PKU) is a rare inherited metabolic disorder requiring lifelong treatment. While early diagnosis and dietary management have substantially improved neurocognitive outcomes, less is known about how PKU affects sexual life, intimate relationships, and reproductive decision-making, particularly during the transition to adulthood.</p><p><strong>Methods: </strong>This cross-sectional study included 152 adolescents and young adults with PKU and 183 age-matched healthy controls. A questionnaire-based approach was used to assess sociodemographic characteristics, sexual behavior, and reproductive attitudes. Additional analyses within the PKU group examined sex- and age-related differences and factors associated with awareness of maternal PKU syndrome.</p><p><strong>Results: </strong>Individuals with PKU differed from controls primarily in psychosocial and reproductive domains rather than in sexual behavior itself. Participants with PKU were more likely to live with parents, less frequently sexually active, and less likely to have children, particularly men. Among sexually active individuals, no significant differences were observed between groups in age at sexual initiation, number of sexual partners, or condom use. Within the PKU cohort, women were more likely to be sexually active, to live independently, to have children, and to report that PKU influenced decisions related to sexual initiation and parenthood. Awareness of maternal PKU syndrome was uneven and strongly associated with female sex, older age, higher education, sexual activity, and parenthood, indicating substantial knowledge gaps among younger individuals and men.</p><p><strong>Conclusions: </strong>PKU appears to be associated with delayed psychosocial transitions and reduced parenthood rather than altered sexual behavior per se. Marked sex differences in reproductive attitudes and disease-related knowledge highlight an unequal distribution of reproductive responsibility. These findings underscore the need to integrate structured sexual and reproductive health education into lifelong care for individuals with PKU, particularly during adolescence and early adulthood.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536601","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 role of lipid metabolism in ALS risk: a Mendelian randomization analysis using GWAS data.","authors":"Houwen Zhang, Chunrong Li, Jialin Yu, Yu Liang, You Wu, Fangzheng Cao","doi":"10.1186/s13023-026-04503-2","DOIUrl":"10.1186/s13023-026-04503-2","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Lipid metabolism is closely related to neuronal function and energy homeostasis, but the genetic association between specific lipid species and ALS risk remains unclear.</p><p><strong>Objective: </strong>This study aimed to investigate the potential causal associations between genetically predicted lipid species and ALS risk using a two-sample Mendelian randomization (MR) approach.</p><p><strong>Methods: </strong>Summary-level GWAS data for 179 lipid species were obtained from 7,174 Finnish participants in the GeneRISK cohort. ALS GWAS data included 29,612 ALS cases and 122,656 controls. The inverse variance weighted (IVW) method was used as the primary MR approach, supplemented by MR-Egger, weighted median, weighted mode, and simple mode analyses. False discovery rate (FDR) correction was applied across all lipid traits based on IVW P values. Sensitivity analyses were conducted to assess heterogeneity, horizontal pleiotropy, and robustness.</p><p><strong>Results: </strong>After FDR correction, genetically predicted higher levels of diacylglycerol (DAG) (18:1_18:1), phosphatidylcholine (PC) (16:1_18:1), PC (18:0_18:1), phosphatidylethanolamine (PE) (O-16:1_18:2), and several triacylglycerol (TAG) species were associated with increased ALS risk. Phosphatidylinositol (PI) (16:0_18:1) showed only a nominal protective association and did not remain significant after FDR correction. Sensitivity analyses did not indicate substantial heterogeneity or horizontal pleiotropy.</p><p><strong>Conclusion: </strong>This MR study provides genetic evidence supporting potential associations between specific lipid species and ALS risk. These findings highlight lipid metabolism as a relevant pathway in ALS susceptibility.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536566","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}