Orphanet Journal of Rare Diseases最新文献

{"title":"Evaluating the relationship between caregiver depression, social support, and children's internalizing and externalizing symptoms in families affected by 22q11.2 deletion syndrome.","authors":"Holly Carbyn, Abiaz Hossain, Raquel L Dias, Lisa D Palmer, Sophie Ayoub, Patricia Lingley-Pottie, Patrick J McGrath, Andrea L Rideout, Andrea Shugar, Cheryl Cytrynbaum, Donna M McDonald-McGinn, Ann Swillen, Anne S Bassett, Sandra Meier","doi":"10.1186/s13023-025-03955-2","DOIUrl":"10.1186/s13023-025-03955-2","url":null,"abstract":"<p><strong>Background: </strong>22q11.2 Deletion Syndrome (22q11DS) is the most common microdeletion syndrome. It exhibits broad phenotypic variability, often including conditions like autism spectrum disorder and intellectual disability. Caregivers of children with 22q11DS are known to be at increased risk of poor mental health and less social support, which might affect their children's health. The current study examined the relationship between parental mental health, perceived social support, and child mental health (internalizing/externalizing symptoms) in children with 22q11DS.</p><p><strong>Method: </strong>Ninety caregivers of children with 22q11DS completed an online survey measuring parental depressive symptoms, perceived social support, and child mental health problems (internalizing and externalizing symptoms). Structural equation models were run to examine the postulated relationships between variables.</p><p><strong>Results: </strong>The caregiver's depressive symptoms were associated with higher internalizing and externalizing symptoms in their children with 22q11DS (mean age 11.8, SD 7.6 years). Caregivers experiencing symptoms of depression were less likely to report strong social support, and lower perceived social support was associated with greater child internalizing and externalizing symptoms. The relationship between caregiver's depressive symptoms and internalizing symptoms in their children was mediated by perceived social support, but no such mediating effects were observed for externalizing symptoms.</p><p><strong>Conclusions: </strong>These findings provide valuable insights into the mental health burdens facing families living with 22q11DS. Interventions focusing on 22q11DS should integrate techniques to foster social and other supports to improve the mental health of caregivers and children.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"442"},"PeriodicalIF":3.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874418","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":"Mitochondrial neurogastrointestinal encephalomyopathy in china: a novel TYMP variant and comprehensive clinical-genetic insights.","authors":"Xuebi Xu, Junhui Xia, Fei Xu, Mingshan Wang, Lihong Yang, Xiaoli Chen","doi":"10.1186/s13023-025-03962-3","DOIUrl":"10.1186/s13023-025-03962-3","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a rare autosomal recessive disorder caused by variants in the TYMP gene, which encodes thymidine phosphorylase (TP). It is characterized by multisystem involvement, with prominent gastrointestinal, neurological, and systemic manifestations that typically exhibit progressive worsening over time.</p><p><strong>Methods: </strong>We characterized a multigenerational MNGIE family through comprehensive proband analysis, identifying compound heterozygous TYMP variants (c.131G > C, p.Arg44Pro and c.1268T>G, p.Leu423Arg in trans) as the molecular basis of disease. Extended family testing for genetic counseling confirmed no secondary pathogenic variants. Muscle biopsies were analyzed using comprehensive staining techniques. Genomic analysis involved next-generation sequencing (NGS) of the proband's DNA and Sanger sequencing of family members' DNA to confirm variants. In silico analysis utilized bioinformatics tools and protein modeling to predict pathogenicity and assess structural impacts, with variant classification adhering to American College of Medical Genetics and Genomics(ACMG) guidelines. Additionally, a literature review of Chinese MNGIE cases was conducted to contextualize the findings.</p><p><strong>Results: </strong>The proband exhibited characteristic MNGIE features, including gastrointestinal dysmotility, diffuse leukoencephalopathy on brain MRI (magnetic resonance imaging), and electrophysiologically confirmed peripheral neuropathy. Muscle biopsy revealed ragged red fibers, cytochrome c oxidase-deficient fibers, and enhanced succinate dehydrogenase activity in blood vessels, consistent with mitochondrial dysfunction. Genetic analysis identified a novel TYMP variant (c.1268T > G, p.Leu423Arg) and a known variant (c.131G > C, p.Arg44Pro) in the proband, both classified as likely pathogenic according to ACMG guidelines. Molecular analysis of other 11 family members detected heterozygous carriers of either the c.1268T > G or c.131G > C variant in six asymptomatic individuals. In silico analysis confirmed that both variants are highly conserved and likely pathogenic. Protein modeling revealed that both variants compromise structural integrity and conformation, impairing TP function. Homozygous or compound heterozygous missense variants were identified as the predominant genetic alterations in 16 Chinese MNGIE cases, with gastrointestinal and neurological symptoms being the most common clinical manifestations.</p><p><strong>Conclusions: </strong>This study enriches the variant spectrum in Chinese patients, highlights the importance of early diagnosis prior to the onset of cachexia and irreversible tissue damage, and enhances the understanding of genetic heterogeneity.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"439"},"PeriodicalIF":3.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874447","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":"A single-centre retrospective study on the clinical characteristics of patients with hereditary angioedema and the therapeutic effect of lanadelumab.","authors":"Yanhua Xu, Yinshi Guo","doi":"10.1186/s13023-025-03988-7","DOIUrl":"10.1186/s13023-025-03988-7","url":null,"abstract":"<p><strong>Background: </strong>Hereditary angioedema (HAE) is a rare monogenic disease, and there are few reports on its clinical characteristics, particularly its drug efficacy, in China. The objective of this study was to gain insight into the clinical characteristics of HAE in Chinese patients, and the efficacy and safety of prophylactic treatment with lanadelumab.</p><p><strong>Results: </strong>The cohort included 22 patients with a median age of 35.0 years (IQR: 27.0-48.3 years). The male-to-female ratio was 1:1.75. The median age at onset was 15.5 years (IQR: 10.0-21.3 years), with a median diagnostic delay of 18.5 years. A significant positive correlation was found between patient age and the duration of diagnostic delay (r = 0.750; p = 0.000). In the cohort, 18 patients (81.8%) had Type I HAE, whereas 4 patients (18.2%) had Type II HAE. The average monthly frequency of attacks was 1.0 (IQR: 0.3, 1.3). Ten patients (45.5%) experienced onset following minor trauma/local bumps/pressure/heat exposure, which was the most common precipitating factor; 7 patients (31.8%) experienced spontaneous onset without apparent precipitating factors. A family history was reported for 16 patients (72.7%). Six patients (27.3%) had concomitant diseases involving various positive autoantibodies or confirmed autoimmune diseases. Eleven patients (50.0%) in this cohort were either currently receiving or had previously received lanadelumab treatment, with a median treatment duration of 7 months (IQR: 3-10 months). Nine patients reached the steady-state period of treatment (> 70 days). Eight patients experienced no oedema attack during treatment. There was a significant reduction in the frequency of attacks and a significant improvement in quality of life by Day 30 (D30) posttreatment, with a decrease of 91.5% in the average monthly frequency of attacks. The average monthly frequency of attacks decreased by 94.6% and 96.2% after 3 months of treatment and at the time of the last injection, respectively, with no life-threatening laryngeal oedema attacks. Only 5 patients (45.5%) experienced local adverse reactions during treatment, and no severe adverse reactions were reported.</p><p><strong>Conclusion: </strong>(1) The median age at onset, diagnostic delay, and precipitating factors in this cohort were consistent with previously reported data from domestic studies. However, the proportion of Type 2 patients was greater than that in prior domestic reports, and a trend towards earlier diagnosis in younger patients was observed; notably, this cohort identified a high proportion (27.3%) of patients with positive autoantibodies or confirmed autoimmune diseases for the first time in China. (2) After treatment with lanadelumab, patients experienced significant improvements in symptoms, quality of life, and anxiety/depression levels. Symptom control was achieved by D30 prior to the drug steady state-period and was maintained throughout the entire treatment period. No seriou","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"441"},"PeriodicalIF":3.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874416","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":"Developments in diagnostic and surgical techniques in children with sagittal suture craniosynostosis: a systematic review spanning the last 30 years.","authors":"Julia Hermann, Christa K Raak, Thomas Ostermann, Wolfram Scharbrodt","doi":"10.1186/s13023-025-03978-9","DOIUrl":"10.1186/s13023-025-03978-9","url":null,"abstract":"<p><strong>Background: </strong>Sagittal suture craniosynostosis is the most usual subtype of craniosynostosis which results from premature fusion of the sagittal suture. It leads to an elongated skull shape known as scaphocephaly. This condition necessitates timely surgical intervention to correct cranial deformities and prevent the associated complications. Over the past three decades, the use of advanced diagnostic methods and the refinement of surgical techniques have improved the understanding of this rare disease.</p><p><strong>Objective: </strong>To analyse the development of surgical interventions and diagnostic methods in children suffering from sagittal suture craniosynostosis over the last three decades.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted in electronic databases Pubmed and online university libraries to identify articles, studies and case reports reporting on surgical interventions and diagnostic procedures for sagittal suture craniosynostosis the period from 1994 to 2024. Clinical studies, case reports, systematic reviews and meta-analyses were assessed and analysed according to inclusion and exclusion criteria. Prisma guidelines for systematic reviews were considered.</p><p><strong>Results: </strong>A systematic literature search identified 301, and a hand search identified 12 articles, of which a total of 57 met the inclusion criteria after careful evaluation. The reviewed studies, predominantly originated from the USA and the Netherlands and provided data on diagnostic methods, surgical techniques, patient-specific characteristics, and outcomes for non-syndromic sagittal craniosynostosis.</p><p><strong>Conclusions: </strong>The evolutionary change in surgical and diagnostic strategies for sagittal suture craniosynostosis reflects the ongoing efforts of the medical community to achieve optimal outcomes for affected children. The selection of the appropriate technique remains an individualized decision, considering age, severity of craniosynostosis and other patient-specific factors.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"437"},"PeriodicalIF":3.5,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874417","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 testing for oral clefts: reflections based on a single Brazilian public genetics service.","authors":"Tamiris Nogueira Bezerra Bueno, Társis Paiva Vieira, Vera Lúcia Gil-da-Silva-Lopes","doi":"10.1186/s13023-025-03967-y","DOIUrl":"10.1186/s13023-025-03967-y","url":null,"abstract":"<p><strong>Background: </strong>Genomic medicine has allowed for an improvement in the diagnosis and molecular understanding of congenital defects. However, its implementation into routine clinical practice demands enormous challenges worldwide. This study describes the etiological diversity and access to genetic diagnosis of individuals with oral clefts (OC) at a single genetics service.</p><p><strong>Results: </strong>This cross-sectional and descriptive study analyzed primary records of the Brazilian Database on Craniofacial Anomalies from 2006 to 2019, before the National Policy of Comprehensive Care for People with Rare Diseases (NPCCPRD) implementation in this service. Among 103 individuals (51 Female and 52 Male), the proportion of syndromic OC (SOC) and non-syndromic OC (NSOC) was 73.8% and 26.2%, respectively, showing that NSOC seems not to be referred for genetic evaluation. Diagnosis occurred in 64/103 (62.13%) cases; 36/64 (56,25%) had clinical diagnoses, of which 27/36 were NSOC. The tests allowing a conclusive diagnosis were whole exome sequencing (WES) (11/20-55.00%), followed by chromosomal microarray analysis (CMA) (4/52-7.69%), Fluorescent in situ hybridization (FISH) (6/21-28.57%), multiplex ligation-dependent probe amplification (MLPA) (2/32-6.25%), and G-banding karyotype (6/72-8.33%). Age at diagnosis ranged from 0 to 46 years (mean = 9.56 /median = 7). Diagnostic investigations of 39/76 SOC cases are still ongoing, relying on clinical follow-up and genetic tests.</p><p><strong>Conclusions: </strong>Etiological diversity reinforces the need for different laboratory resources and clinical follow-up. These results and reflections about the need to implement Genomic Medicine are of universal interest. They also show the need to improve public health policies for genetic evaluation, diagnostic tests, and genetic counseling for an effective NPCCPRD.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"435"},"PeriodicalIF":3.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862391","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":"Health care supply in patients with Ehlers-Danlos syndromes and generalized hypermobility spectrum disorder: a German perspective.","authors":"Jonas Rauterberg, Marie Hock, Nikolaus Kernich, Arim Shukri, Henning Klapproth, Vanessa Löw, Michaela Henning, Iliana Tantcheva-Poór","doi":"10.1186/s13023-025-03937-4","DOIUrl":"10.1186/s13023-025-03937-4","url":null,"abstract":"<p><strong>Background: </strong>Diagnosing Ehlers-Danlos syndromes (EDS) and EDS-related \"hypermobility spectrum disorder\" (HSD) is challenging and cutaneous manifestations often serve as indicators of these rare connective tissue disorders. Only limited data exist on the healthcare of EDS/HSD in Germany as specialized services have been missing and a national register is not available.</p><p><strong>Objectives: </strong>In 2020, a dermatologic-orthopedic EDS outpatient service was initiated at the University Hospital of Cologne, Germany. The objectives of the present survey were to examine the \"medical journey\" and the disease burden of our patients.</p><p><strong>Methods: </strong>A pseudonymized paper survey was sent to all adults who were diagnosed with hypermobile EDS (hEDS), classical EDS (cEDS), classical-like EDS (clEDS) or generalized HSD at the EDS Cologne service from December 2021 until May 2023.</p><p><strong>Results: </strong>Of the 99 participants, 80 were diagnosed with hEDS/HSD, 16 with cEDS and 3 with clEDS. The mean time to diagnosis was 22.0 years (14.5 years for cEDS/clEDS vs. 23.0 years for hEDS/HSD). 24.2% of the participants had a recognized degree of disability of ≥ 50, the average sick leave in the last 3 months was 4.6 days for cEDS/clEDS and 21.3 days for hEDS/HSD. 44.9% of the hEDS/HSD patients reported on having at least four comorbidities compared to 21.1% in the cEDS/clEDS group (p = 0.023). At least 15 medical specialties were involved in the diagnostics and treatment of participants with multiple therapeutic modalities.</p><p><strong>Conclusions: </strong>This is the first study providing an insight on the healthcare supply of EDS/HSD patients in Germany. Participants in our survey had a much longer \"diagnostic journey\" than the one in previous studies and suffered from high morbidity despite high healthcare utilization. Our results point to the urgent necessity of a better coordinated, multidisciplinary care for patients with these complex genodermatoses including innovative political structures, further research and international networking.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"436"},"PeriodicalIF":3.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862392","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":"Anti-MDA5 antibody IgG1 subtype is associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis.","authors":"Yun Wu, Yue Wang, Yulu Qiu, Chengying Lv, Yujing Zhu, Lei Wang, Lingxiao Xu, Hanxiao You, Fang Wang, Wenfeng Tan","doi":"10.1186/s13023-025-03921-y","DOIUrl":"10.1186/s13023-025-03921-y","url":null,"abstract":"<p><strong>Background: </strong>Rapidly progressive interstitial lung disease (RP-ILD) is a severe, often fatal complication in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5⁺ DM). Early prediction of RP-ILD still remains challenging. We aimed to explore the link between anti-MDA5 IgG subtypes and ILD prognosis in individuals with MDA5⁺ DM.</p><p><strong>Methods: </strong>In a retrospective study involving 71 MDA5⁺ DM-ILD patients, initial serum titers of anti-MDA5 IgG subtypes were measured using indirect immunofluorescence. We then analyzed the associations between these IgG subclasses and the development of RP-ILD.</p><p><strong>Result: </strong>Of the 71 patients, 30% developed RP-ILD. RP-ILD patients had a shorter disease course and a higher mortality rate than non-RP-ILD patients (both P < 0.001). A notable link was found between RP-ILD and anti-MDA5 IgG1 (P < 0.05), with 100% of RP-ILD patients showing IgG1 titers ≥ 1:100. Additionally, IgG3 positivity was more prevalent in RP-ILD (P < 0.05). Multivariate logistic regression analysis identified high titers of anti-MDA5 IgG1 and a high neutrophil-lymphocyte ratio (NLR^high≥5.22) as independent risk factors for RP-ILD (P = 0.020, 0.017, respectively). The combination of anti-MDA5 IgG1 ≥ 1:100 with an NLR ≥ 5.22 improved the predictive accuracy for RP-ILD, yielding an AUC of 0.80.</p><p><strong>Conclusions: </strong>Elevated anti-MDA5 IgG1 titers are strongly related to RP-ILD in MDA5⁺ DM and function as an important marker for early detection of individuals at high risk. Combining anti-MDA5 IgG1 levels with NLR further enhances predictive accuracy for RP-ILD, offering a practical approach for clinical monitoring and early intervention.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"434"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859519","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 self-counselors in Tunisia: the role of health education in hemoglobinopathies prevention among high school students.","authors":"Foued Maaoui, Imen Moumni, France Arboix-Calas, Ines Safra, Samia Mnif","doi":"10.1186/s13023-025-03958-z","DOIUrl":"10.1186/s13023-025-03958-z","url":null,"abstract":"<p><strong>Background: </strong>In Tunisia, the primary prevention of hemoglobinopathies relies on behavioral changes related to screening and genetic counseling. The progression in cognitive and functional literacy in human genetics serves as a crucial aspect of this transformation. In this study, we consider the possibility of genetic self-counseling, checking it in students with scientific or literary backgrounds.</p><p><strong>Methods: </strong>To assess potential for genetic self-counseling applied to sickle cell disease (SCD), we designed a questionnaire on SCD knowledge (SCDKA), then recruited 356 students (200 scientific students vs. 165 literary students). Since and there were no previous standards for classifying students according to their SCDKA score, we considered participants with an SCDKA score ≥ 70% correct answers as having a high literacy level. Statistical analysis of the results was carried out using chi-square tests and Fisher's, to compare the demographic and educational characteristics of the participants.</p><p><strong>Results: </strong>The analysis of responses to the various SCDKA items shows a lack of awareness about the hereditary origin of hemoglobinopathies. 97.8% of respondents did not recognize electrophoresis as a diagnostic technique. In terms of genetic literacy, the autosomal and recessive nature of hemoglobinopathies is not well understood. This explains why 41% and 74% of these students could not answer items on genetic transmission. The perception of controllability of hereditary diseases is higher among science students, as is the intention to inform their partner before procreation (56.5% vs. 24.35%, p < 0.001). Responses reveal that science section respondents have higher proactive preventive intentions compared to literature section students, as they recognize the usefulness of genetic counseling (75.5% vs. 47.43%, p < 0.001), premarital diagnosis (57.5% vs. 18.59%, p < 0.001), and prenatal diagnosis (61.5% vs. 13.46%, p < 0.001).</p><p><strong>Conclusion: </strong>Currently, levels of health literacy and functional genetic literacy do not ensure genetic self-counseling for hemoglobinopathies prevention. The survey shows that having a scientific background was an advantage, but a detailed analysis of these students' results reveals average to low SCDKA scores.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"426"},"PeriodicalIF":3.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144848210","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":"A cost-utility analysis of newborn screening for spinal muscular atrophy in Canada.","authors":"Alex Pace, Weston Roda, Corrina Poon, Hugh J McMillan, Maryam Oskoui, Alex MacKenzie, Pranesh Chakraborty, Jeff Round","doi":"10.1186/s13023-025-03927-6","DOIUrl":"10.1186/s13023-025-03927-6","url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by the loss of the SMN1 gene, with an estimated birth prevalence of about 1 in 10,000. Early intervention with disease-modifying therapies (DMTs) significantly improves outcomes. This study evaluates the economic implications and health benefits of newborn screening (NBS) for SMA in Canada from the societal perspective.</p><p><strong>Methods: </strong>A decision analytic model was developed, which combined a decision tree for the screening algorithm and a Markov model for long-term health outcomes. The Markov model included health states based on WHO motor milestones. The population cohort of 357,903 live newborns reflects the 2022-2023 births in Canada. Screening is performed on dried blood spot testing which evaluates for biallelic deletions in SMN1. Cost inputs encompassed treatment and health state costs, while utility values reflected quality of life in each health state.</p><p><strong>Results: </strong>NBS for SMA is expected to identify 37.1 (95% CI: 15.0, 70.7) newborns annually in Canada. Our analysis over a lifetime horizon and a discount rate of 1.5% shows NBS and early treatment has an incremental cost of -$146,187,000 (95% CI: -249,773,777 to - 17,890,034) and incremental benefit of 872 (95% CI: -193, 2329) quality-adjusted life years (QALYs) compared to no NBS and late treatment. This resulted in a mean ICER value of -$173,572/QALY.</p><p><strong>Conclusion: </strong>The decision analytic model indicated that overall NBS is cost-saving and more effective than no NBS and late treatment in the Canadian health system.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"428"},"PeriodicalIF":3.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144848204","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 characteristics and long-term outcomes of 101 patients with urea cycle disorders in China.","authors":"Ziyan Cen, Pingping Ge, Yuhe Chen, Ting Zhang, Peiyao Wang, Lingwei Hu, Benqing Wu, Xinwen Huang","doi":"10.1186/s13023-025-03985-w","DOIUrl":"10.1186/s13023-025-03985-w","url":null,"abstract":"<p><strong>Background: </strong>Urea cycle disorders (UCDs) are a group of rare genetic metabolic disorders characterized by hyperammonemia, which can lead to neurological damage, systemic complications, and even death. Understanding UCDs' clinical features and progression in the Chinese population will fill research gaps and benefit patients globally.</p><p><strong>Methods: </strong>This retrospective study evaluated the clinical, biochemical, genetic characteristics, and long-term outcomes in 101 Chinese patients with six subtypes of UCDs between 2007 and 2024. Data were collected from medical records and analyzed.</p><p><strong>Results: </strong>The overall survival rate was 93.0% among UCD patients. An equal gender ratio was observed in ornithine transcarbamylase deficiency. Newborn screening (NBS) was conducted in this cohort, and 57.0% of patients were diagnosed through NBS. Neurological and gastrointestinal symptoms were the most common. Symptoms often appeared within the first year, especially in the first month. Arginine was the most frequently used treatment, with glycerol phenylbutyrate often used as a nitrogen scavenger in severe cases. Biochemical analysis showed subtype-specific differences, including notable declines in leucine and glycine on low-protein diets. Genetic analysis revealed a wide distribution of mutations, with few hotspots and 17 newly identified mutations. Clinically diagnosed patients had worse outcomes than those diagnosed via newborn screening.</p><p><strong>Conclusion: </strong>This study is the first to describe the clinical features and long-term outcomes of UCDs in a large sample of Chinese patients, highlighting the importance of newborn screening for early diagnosis and improved treatment outcomes.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"432"},"PeriodicalIF":3.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144848205","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}