Orphanet Journal of Rare Diseases最新文献

{"title":"An ALG12-CDG patient with a novel homozygous intronic mutation associated with low ALG12 mRNA.","authors":"Sandrine Vuillaumier-Barrot, Thierry Dupré, Tiffany Andriantsihoarana, Vincent Desportes, David Cheillan, Stuart E H Moore, Isabelle Chantret","doi":"10.1186/s13023-025-03535-4","DOIUrl":"10.1186/s13023-025-03535-4","url":null,"abstract":"<p><strong>Background: </strong>Type I Congenital Disorders of Glycosylation (CDG-I) are inherited diseases presenting deficits in protein N-glycosylation involving either the biosynthesis of the lipid-linked oligosaccharide Glc₃Man₉GlcNAc₂-PP-dolichol or transfer of its oligosaccharide to protein.</p><p><strong>Results: </strong>We describe a patient harbouring hypoglycosylated transferrin, a characteristic of CDG-I. NGS revealed a homozygous RFT1 (c.16G > T p.Val6Leu) variant of unknown significance that is predicted to be benign. Metabolic radiolabelling of the patient's fibroblasts did not reveal the accumulation of truncated Man₅GlcNAc₂-PP-dolichol expected of RFT1-CDG but rather an accumulation of Man₇GlcNAc₂-PP-dolichol, characteristic of ALG12-CDG. Revaluation of the NGS data revealed a homozygous (22_50311909A_G, c.-79 + 2 T > C) variant that modifies the second nucleotide of the first intron of the ALG12 gene upstream of the first coding exon (exon 2). Sequencing of ALG12 cDNA revealed a 4-base insertion between exon 1 and exon 2 suggesting a shift in mRNA splicing in this intron to a putative new GU donor site. The patient's fibroblasts display 3% of control ALG12 mRNA levels.</p><p><strong>Conclusion: </strong>This is the first description of a pathogenic intronic ALG12 variant upstream of the first coding exon. The modification of the splicing process between intron 1 and exon 2, the very low transcript level and the absence of other mutations in the patient's ALG12 gene lead us to conclude that this ALG12 variant is a predicted Loss of Function (pLOF) variant.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"81"},"PeriodicalIF":3.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472766","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":"The economic impact of caregiving for individuals with Angelman syndrome in the United States: results from a caregiver survey.","authors":"John Jarvis, Elizabeth Chertavian, Marric Buessing, Taylor Renteria, Lufei Tu, Lauren Hoffer, Ryan Fischer, Amanda Moore, Meagan Cross, Megan Tones","doi":"10.1186/s13023-025-03551-4","DOIUrl":"10.1186/s13023-025-03551-4","url":null,"abstract":"<p><strong>Background: </strong>Angelman syndrome (AS) is a rare neurogenetic disorder characterized by persistent cognitive and functional impairments that necessitate lifelong care. Caring for individuals with AS leads to substantial household costs, as well as impacts on work productivity, leisure time, and quality of life for caregivers. The economic value of these impacts in the United States (US) has not been well studied. We conducted a survey of US caregivers for persons with AS to quantify the annual economic impact of caregiving. Information on AS-related economic impacts was gathered, including household costs, employment impacts, leisure time loss, and caregiver healthcare costs. The survey did not gather information on direct medical care costs borne by healthcare insurers or other economic impacts to the US government and other stakeholders.</p><p><strong>Results: </strong>A total of 105 caregivers completed the survey and 105 individuals with AS were represented. Most caregivers were female (89.5%), white (83.8%), and identified as the primary caregiver (75.2%). Most individuals with AS represented in the sample were age < 18 (82.9%). The annual economic impact of caregiving for persons with AS averaged $79,837 (SD $55,505). Costs related to employment impacts and lost work productivity in the past 12 months accounted for most (53%) of this impact and averaged $42,697 (SD $28,309). Household costs incurred in the past 12 months for goods and services to better accommodate individuals with AS were $29,680 (SD $47,753). Leading contributors included vehicle purchases and modifications (mean $6,717; SD $17,791), professional caregiving (mean $6,123; SD $17,335), home modifications and repairs (mean $4,387; SD $15,734), and supportive therapy (mean $3,269; SD $7,564). Economic impacts in the past 12 months from lost leisure time and incremental healthcare costs for caregivers were estimated to be $6,634 (SD $4,652) and $827 (SD $2,072), respectively.</p><p><strong>Conclusions: </strong>Caregivers incur substantial costs to accommodate individuals with AS, as well as substantial impacts related to employment and leisure time. This study's findings may be utilized in future research to better estimate the value from therapeutic advances in AS and direct resources toward mitigating economic impacts for households.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"82"},"PeriodicalIF":3.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476804","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":"Genotypes and different clinical variants between children and adults in progressive familial intrahepatic cholestasis: a state-of-the-art review.","authors":"Giovanni Vitale, Marco Sciveres, Claudia Mandato, Adamo Pio d'Adamo, Angelo Di Giorgio","doi":"10.1186/s13023-025-03599-2","DOIUrl":"10.1186/s13023-025-03599-2","url":null,"abstract":"<p><strong>Introduction: </strong>Progressive Familial intrahepatic cholestasis (PFIC) are rare disorders of bile acid (BAs) secretion and transport with a genetic background. PFIC are paediatric manifestations, but the same variants causing PFIC can also cause cholestasis with a later paediatric onset or adult-onset cholestatic disease (AOCD). Pruritus is a symptom of cholestasis that can be so devastating that it requires a liver transplant (LT) in children; some PFIC types have been described as at risk of liver cancer development. Commonly prescribed medications for PFIC symptoms can partially relieve pruritus without changing the natural history of the disease. Recently, a therapy reducing the intestinal resorption of BAs has been approved; it is effective on both pruritus and cholestasis in PFIC, potentially being a disease-modifying intervention.</p><p><strong>Areas covered: </strong>The clinical and genetic characteristics of different PFIC and AOCD are summarized to provide a common background for geneticists and paediatric and adult hepatologists in diagnosis and management.</p><p><strong>Expert opinion: </strong>Collaboration between paediatric and adult hepatologists and geneticists will become crucial for cholestatic disease research and patient treatment. Therefore, adult hepatologists will need to learn more about FIC. This might enable the implementation of individualized surveillance in FIC patients and the evaluation of patient family histories.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"80"},"PeriodicalIF":3.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472769","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":"Helping the medicine go down: the role of the healthcare professional in a young person's experience of achalasia, a rare oesophageal motility disorder.","authors":"Geena Capps","doi":"10.1186/s13023-025-03571-0","DOIUrl":"10.1186/s13023-025-03571-0","url":null,"abstract":"<p><p>Young patients can be uniquely vulnerable to the impacts of a rare disease, diagnosed in their critical years of identity formation, social development, and planning for the future. Drawing from my journey as both a rare disease patient and a medical student, this essay explores how the rare disease achalasia has shaped my life, alongside the experiences of another young patient, Isobel. Most importantly, this essay highlights the critical role that individual healthcare professionals play in shaping young patients' experiences of their condition. Although diagnosing and managing rare diseases can be challenging due to limited research and awareness, my own experiences demonstrate that individual, intentional changes can have profound impacts. By engaging with and believing young patients, individual healthcare providers can reduce misdiagnoses, alleviate isolation and uncertainty, and ultimately, improve healthcare outcomes for young people with rare diseases.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"72"},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458746","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":"Impact of enzyme replacement therapy and migalastat on disease progression in females with fabry disease.","authors":"Malte Lenders, Albina Nowak, Markus Cybulla, Jessica Kaufeld, Anja Friederike Köhn, Nicole Maria Muschol, Christine Kurschat, Eva Brand","doi":"10.1186/s13023-025-03600-y","DOIUrl":"10.1186/s13023-025-03600-y","url":null,"abstract":"<p><strong>Aim: </strong>The aim of our multicenter study was to investigate the safety and efficacy of enzyme replacement therapy (ERT) and chaperone therapy on the disease progression in female Fabry disease (FD) patients and to compare the individual treatment regimens.</p><p><strong>Methods: </strong>Data from 3 consecutive visits of 102 female FD patients from 6 Fabry centers were retrospectively analyzed. According to their FD-specific treatment, patients were separated in 5 groups: Newly agalsidase-beta- [n = 18], agalsidase-alfa- [n = 29] and migalastat-[n = 14] treated patients, and long-term agalsidase-beta- [n = 7] and agalsidase-alfa-[n = 34] treated patients. Clinical presentation and laboratory data, including plasma lyso-Gb₃ levels were assessed.</p><p><strong>Results: </strong>Treatment with agalsidase-beta, agalsidase-alfa, and migalastat was safe and severe adverse events were rare. Newly and long-term-treated patients presented a stable disease course over time. None of the patients required hospitalization due to cardiac events. Overall septum thickness remained stable in all groups (p > 0.05). Estimated glomerular filtration rate (eGFR) only slightly decreased in patients treated with agalsidase-alfa [newly- and long-term-treated: -1.5 ± 3.2 and - 1.3 ± 3.9 ml/min/1.73 m²/year; p = 0.0056 and p = 0.0187, respectively] but the decrease was in the range of natural eGFR decline. eGFRs in agalsidase-beta and migalastat-treated patients were stable. No clinically relevant differences concerning treatment efficacy between agalasidase-beta, agalsidase-alfa, and migalastat were detected.</p><p><strong>Conclusion: </strong>We conclude that treatment of females with agalsidase-beta, agalsidase-alfa, and migalastat was safe. Independent of the chosen treatment regimen, nearly all patients presented with a stable disease course over time. In our cohort, a comparison of therapy efficacies showed no relevant clinical differences between the groups.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"79"},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468416","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":"Illness cognition, illness perception and related factors in patients with lymphangioleiomyomatosis.","authors":"Liting Huang, Lulu Yang, Ruoyun Ouyang, Siying Ren","doi":"10.1186/s13023-025-03566-x","DOIUrl":"10.1186/s13023-025-03566-x","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the self-perceived illness cognition and perception status, as well as the relevant factors among lymphangioleiomyomatosis (LAM) patients.</p><p><strong>Methods: </strong>A web-based questionnaire survey was conducted in September 2023. A total of 121 LAM patients participated (including 16 patients with TSC-LAM), and the survey collected general demographic information, responses to a disease cognition questionnaire, and a simplified disease perception questionnaire.</p><p><strong>Results: </strong>LAM patients have a higher level of negative illness cognition and a lower level of positive illness cognition, specifically characterized by helplessness (15.74 ± 4.68 points), acceptance (16.00 ± 3.28 points), and perceived benefits (16.92 ± 3.86 points). Single-factor analysis of variance found significant correlations between cultural level, age, family average monthly income, use of rapamycin, use of home oxygen therapy, hospitalization frequency, disease duration, severity of respiratory distress, activity limitation, and the helplessness score of LAM patients (p ≤ 0.05); the number of children was significantly associated with acceptance scores of LAM patients (p ≤ 0.05); and whether surgery had been performed was significantly associated with acceptance and perceived benefits scores of LAM patients (p ≤ 0.05). Disease duration and activity limitation entered the regression equation for helplessness dimension, while whether surgery had been performed entered the regression equation for perceived benefits dimension, but no factor entered the regression equation for acceptance dimension. Applying the same analysis to disease perception, we found that the average score of the Illness Perception Questionnaire was 45.43 ± 8.97, with lower scores in the reverse-scored items of individual control, treatment, and understanding.</p><p><strong>Conclusions: </strong>LAM patients exhibit higher levels of helplessness, particularly among those with longer disease duration and greater activity limitations, leading to a more negative perception of the disease. Additionally, patients who have undergone surgical procedures tend to perceive fewer benefits. Furthermore, there is a significant correlation between illness perception and factors such as rapamycin usage, home oxygen therapy, disease duration and activity limitations caused by LAM. This indicates that clinical healthcare providers should pay more attention to LAM patients and their associated groups, providing both informational and psychological support.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"78"},"PeriodicalIF":3.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458748","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":"Bone disease and oromaxillofacial disorders: a cross- sectional study in a Tanzanian pediatric population.","authors":"Elias Isaack Mashala, Lluís Brunet-Llobet, Anastasiya Lapitskaya, Sol Balsells-Mejía, Ombeni Mrina, Jaume Miranda-Rius","doi":"10.1186/s13023-025-03563-0","DOIUrl":"10.1186/s13023-025-03563-0","url":null,"abstract":"<p><strong>Background: </strong>Certain bone diseases of congenital origin are associated with dental alterations and with oromaxillofacial (OMF) disorders. The objective of this study was to evaluate and compare the OMF alterations presented by patients affected by bone pathology with respect to a healthy population from the same geographical environment.</p><p><strong>Material & methods: </strong>A cross-sectional study was carried out at Mount Meru Regional Referral Hospital and Kaloleni secondary school in Arusha, Tanzania. The patients with bone pathologies (n = 60) were consecutively recruited from the hospital, while the controls (n = 581) comprised a population of healthy students from the school, which was located in the same neighbourhood as the hospital. In the case group, the different bone pathologies were divided into two subgroups: (i) disorders in cellular metabolism (DCM); and (ii) disorders of bone growth/deformity (DGD). Musculoskeletal and oral clinical examinations were performed in both groups.</p><p><strong>Results: </strong>The case group presented significantly higher values of moderate and severe inflammation on the Löe & Silness Gingival Index (GI 2: 65%, GI 3: 25%) than the control group (p < 0.001), where mild inflammation predominated (GI 1: 88%). The case group also had higher scores for decayed, missing and filled teeth. Dental fluorosis was reported in 75.2% of controls and in only 26.6% of cases, the differences being clearly significant (p < 0.001). Significant differences for fluorosis were also reported between the two subgroups (p < 0.001), with a higher incidence for the DCM subgroup (43.8%). Twenty-two patients (36.7%) in the case group displayed clinical absence of teeth: the rate was significantly higher in the DGD subgroup (n = 15, 50%) than in the DCM subgroup (n = 8, 25%) (p = 0.045). In relation to the type of dental occlusion, the group with bone pathology presented a significant predominance of Angle class II - III malocclusions (p < 0.001). Craniofacial abnormalities were more frequent in the DGD subgroup, although the difference was not significant. The spine was normal in 41 patients (68.3%) and the differences between subgroups were not significant. Pathological fractures were significantly more frequent in the DGD subgroup (50% vs. 6.3%; p < 0.001). Assessing whether there was a relationship between malocclusion and skeletal deformities (spine and upper limb) in the case group, subjects with upper limb deformity (n = 16) presented significant differences for inverted overjet (p = 0.031).</p><p><strong>Conclusion: </strong>Patients with bone disease had worse oral health and more severe dental malocclusion than controls. The results presented here may help to raise awareness among orthopedic and pediatric professionals of abnormalities related to OMF conditions in childhood.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"77"},"PeriodicalIF":3.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441574","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 outcomes and drug utilisation in children with Noonan syndrome: a European cohort study.","authors":"Michele Santoro, Ingeborg Barisic, Alessio Coi, Joachim Tan, Ester Garne, Maria Loane, Ljubica Odak, Maria Valentina Abate, Elisa Ballardini, Clara Cavero-Carbonell, Miriam Gatt, Mika Gissler, Kari Klungsøyr, Nathalie Lelong, David Tucker, Diana Wellesley, Joan K Morris","doi":"10.1186/s13023-025-03594-7","DOIUrl":"10.1186/s13023-025-03594-7","url":null,"abstract":"<p><strong>Background: </strong>Noonan Syndrome (NS) is a rare multisystemic disorder with heterogeneous phenotypic manifestations. The aim of this study was to analyse rates of survival, hospitalisation, surgeries and prescriptions in children born with NS in the first 10 years of life.</p><p><strong>Methods: </strong>This is a multi-centre population-based cohort study. Data on 175 liveborn children diagnosed with NS from 11 EUROCAT congenital anomaly registries were linked to healthcare databases. Each registry applied a common data model to standardise data and run common syntax scripts to produce aggregated results which were pooled using random effects meta-analyses.</p><p><strong>Results: </strong>Mortality rates were high in the first year of life with 5.4% (95%CI 1.5%-10.1%) of children dying before the age of 1 year with a further 2% dying up to age 5. In the first year, 87.9% (95%CI 75.3%-94.3%) of children were hospitalized and the median Length Of hospital Stay (LOS) was 15.3 days (95%CI 9.3-21.2). After the first year, the proportion of children hospitalized remained higher than 70%, but the LOS decreased to 1.3 days per year. In the first 5 years, 65.2% of children underwent a median of two surgical procedures. The median age at first surgery was 29 weeks. The proportion of children with an antibiotic prescription increased from 53.6% at age 1 to 62.4% yearly until 4 years of age.</p><p><strong>Conclusions: </strong>Children with NS have high mortality and morbidity not only in the first year of life but also up to five years of age. This study evaluated the health burden of NS and provided information for clinicians, health-care providers and families.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"76"},"PeriodicalIF":3.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441576","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":"The healthcare burden of pulmonary alveolar proteinosis (PAP).","authors":"Elinor Lee, Ali Ataya, Cormac McCarthy, Erica Godart, John Cosenza, Alysse King, Brian Robinson, Tisha Wang","doi":"10.1186/s13023-024-03478-2","DOIUrl":"10.1186/s13023-024-03478-2","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary alveolar proteinosis (PAP) is a rare lung syndrome characterized by the accumulation of surfactant in the alveoli. Using a longitudinal claims database, we compared measures of clinical and economic burden between a sample of diagnosed PAP patients and non-PAP matched controls.</p><p><strong>Methods: </strong>PAP patients were identified leveraging IPM.ai's longitudinal U.S. claims database spanning January 1, 2009, through May 1, 2022. PAP patients were selected based on the presence of ICD-10: J84.01 or ICD-9: 516.0 in their claims history and were indexed for observation. An age, gender, and geographically matched control cohort was created (ratio of 1:4) for comparison. A third cohort, consisting of likely undiagnosed PAP patients, was identified using a machine learning model. The PAP and control cohorts were tracked longitudinally, depending on individual index dates, from January 1, 2018, through May 1, 2023. Inclusion criteria required evidence of continual claims activity 12 months prior to and after the index date, which reduced the total number of diagnosed PAP and control patients in the analysis. Demographics, comorbidities, procedures, medication use, annual healthcare resource utilization (HCRU), and costs were calculated for eligible PAP and control patients and were compared 12 months prior to, and 12 months after each patient's index date.</p><p><strong>Results: </strong>After inclusion criteria were applied, 2312 confirmed PAP patients and 9247 matched controls were included in the analysis. Compared with matched controls, PAP patients had significantly higher rates of diagnosed conditions at baseline as defined by the Charlson Comorbidity Index (CCI). During the follow-up period, PAP patients had higher rates of diagnosed conditions, procedures, medication use, and cost-of-care compared with controls. PAP patients also had higher rates of emergency room visits (35% vs. 14%; P < 0.001), outpatient visits (87% vs. 56%; P < 0.001), inpatient visits (20% vs. 5%; P < 0.001) and had longer lengths of stay for inpatient hospitalizations (2.8 days vs. 0.56 days; P < 0.001), respectively.</p><p><strong>Conclusion: </strong>This study represents the largest dataset of PAP patients and matched controls to be analyzed to date. Findings indicate that PAP patients have higher rates of diagnosed conditions, procedures, medication use, HCRU, and costs compared with non-PAP patients.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"73"},"PeriodicalIF":3.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425896","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 evidence for Pompe disease remains fragmented. Comment on \"A rare partnership: patient community and industry collaboration to shape the impact of real-world evidence on the rare disease ecosystem\" by Klein et al.","authors":"Michelle E Kruijshaar, Tiffany House, Benedikt Schoser, Pascal Laforêt, Maudy T M Theunissen, Stephan Wenninger, Thomas Hundsberger, Jordi Diaz-Manera, Ans T van der Ploeg, Nadine A M E van der Beek","doi":"10.1186/s13023-025-03552-3","DOIUrl":"10.1186/s13023-025-03552-3","url":null,"abstract":"<p><p>In a recent publication by Klein et al., the need for real-world data on rare diseases is highlighted. We strongly support this need, and the collaboration with the patient community to collect data, as promoted in this publication. Our concern, however, is that this paper may be misunderstood as suggesting that the Sanofi-run Rare Disease Registries (RDRs) are sufficient to provide the datasets needed to evaluate current and future therapies. Industry-driven registries focus on their own product(s) and, therefore, do not provide the opportunity to compare products from different companies. Today, multiple companies produce treatments for all diseases included in the RDRs. Each company will have to run its own registry for regulatory purposes. This will lead to data fragmentation, which is prohibitive of truly understanding the effects of the various treatment options for these rare diseases. Therefore, independently funded and owned registries are essential to generate real-world evidence (RWE) unrelated to specific products. We discuss options for this for Pompe disease, including the International Pompe Survey, which has collected patient-reported outcomes independently from industry since 2002. This letter aims to raise awareness of the problem of siloed data and advocate for a new way forward where independent registries provide post-marketing surveillance data.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"74"},"PeriodicalIF":3.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425766","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}