Public Health Genomics最新文献

{"title":"Implementing Genomic Medicine in a Federally Qualified Health Center: Assessing Readiness through a Mixed-Methods Approach.","authors":"Emory William Heffernan, Paramita Das, Larry Hearld, Catanya G Stager, Samantha Whitfield, Irene Moss, Tiffany Osborne, Alex Zayzafoon, Christopher Mosely, Bruce Korf, Nita Limdi, Lori Brand Bateman","doi":"10.1159/000551310","DOIUrl":"10.1159/000551310","url":null,"abstract":"<p><strong>Introduction: </strong>Genomic medicine enables early detection of treatable conditions and supports personalized care across all populations; however, evidence guiding its implementation in resource-constrained healthcare settings remains limited.</p><p><strong>Methods: </strong>Using a mixed-methods approach, this study evaluated the readiness of an Alabama Federally Qualified Health Center (FQHC) to implement genomic medicine as part of routine clinical care. Staff members (e.g., physicians, nurses, medical assistants, and administrators) completed surveys, individual interviews, a concept mapping session, and a nominal group technique exercise.</p><p><strong>Results: </strong>Study participants included 13 clinic members. Interviews and mapping revealed three dominant barriers: staffing shortages, financial constraints, and language obstacles. Facilitators included a strong commitment to quality care, alignment with the clinical mission, and supportive leadership. Survey results (N = 12) revealed mean scores in the positive range for culture, learning climate, and leadership engagement, whereas scores for stress, available resources, and readiness for change were nearer to the neutral midpoint, suggesting potential practical constraints on genomic implementation. The use of the CFIR-ERIC Implementation Strategy Matching Tool allowed the team and participants to evaluate nine candidate strategies, prioritizing those with high feasibility and impact. The evaluation was visually developed into an impact matrix which placed patient and family involvement, tailored educational materials, educational meetings, and designated genomic medicine leadership in the high-feasibility/high-impact quadrant. These strategies directly address identified barriers and fit existing clinical strengths, which is important for equitable precision-medicine adoption.</p><p><strong>Conclusion: </strong>Findings indicate that FQHCs can advance genomic services through culturally attuned patient engagement, structured provider training, and clear leadership roles.</p>","PeriodicalId":49650,"journal":{"name":"Public Health Genomics","volume":" ","pages":"109-121"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147391535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Views on a Chatbot for Cancer Family History Collection among Leaders of Hispanic and Pacific Islander Communities in Utah.","authors":"Melissa Guziak, Daniel Chavez-Yenter, Emma Sears, Amanda Gammon, Crystal Y Lumpkins, Whitney F Maxwell, Lynette Phillips, Peter Taber, Guilherme Del Fiol, Kimberly A Kaphingst","doi":"10.1159/000550466","DOIUrl":"10.1159/000550466","url":null,"abstract":"<p><strong>Introduction: </strong>Individuals from historically marginalized communities have less access to genetic testing services. Incomplete family history information in electronic health records contributes to under-identification of those eligible for genetic testing of hereditary cancer genes. Digital health tools can aid in collecting family history information, but there is a lack of information about how to integrate these tools in ways that are effective for different communities. This study investigated experiences with family history collection as well as acceptability and approaches for cultural adaptation of a chatbot for family history collection.</p><p><strong>Methods: </strong>Seven community engagement studios were conducted with community leaders (N = 48) representing historically marginalized communities, specifically Hispanic and Pacific Islander. The studios were conducted by trained facilitators in English (n = 4) or Spanish (n = 3) with 5-8 participants per studio. Transcripts of recorded studios were analyzed using inductive thematic analysis.</p><p><strong>Results: </strong>Two domains, each with underlying themes, were identified: (1) previous family history collection experience and (2) chatbot impressions and feedback. Community leaders saw value in using a chatbot for family history collection and also expressed the importance of addressing accessibility of the tool. They emphasized interpersonal interactions together with the use of digital health tools and the importance of trusting relationships with healthcare professionals regardless of chatbot integration.</p><p><strong>Conclusion: </strong>Community leaders highlighted specific strengths and limitations of the chatbot. The importance of human connection with healthcare professionals to build trusting relationships was emphasized. Successful integration of this tool into historically marginalized communities will require ongoing conversations and investment in communities.</p>","PeriodicalId":49650,"journal":{"name":"Public Health Genomics","volume":" ","pages":"55-72"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Path to Screening US Newborns for Severe Combined Immunodeficiency, 1968-2018: A Narrative Review of a Successful Biomedical Research and Public Health Partnership.","authors":"Scott D Grosse, Robert F Vogt, Golriz K Yazdanpanah, Kee Chan, Marcus Gaffney, Anne M Comeau","doi":"10.1159/000551379","DOIUrl":"10.1159/000551379","url":null,"abstract":"<p><strong>Background: </strong>Newborn screening for severe combined immunodeficiency (SCID) represents an important advancement in public health genomics as the first DNA-based primary screening test in newborn screening programs. The story of how this process took place in the USA during the first two decades of the current century can provide useful lessons for the fields of newborn screening and public health genomics.</p><p><strong>Summary: </strong>Newborn screening for SCID was officially recommended at the national level in the USA in 2010 and fully implemented by 2018. It was preceded by the development and evaluation of treatments administered to infants with SCID at varying ages. Evidence of better outcomes with early treatment by hematopoietic stem cell transplantation, published beginning in 1998, led to the exploration of practical screening assays beginning in 2001, followed by pilot screening studies conducted beginning in 2008, and full implementation in US screening programs between 2010 and 2018. Technical, logistical, and funding challenges in implementing the needed genomic technologies in public health programs were met through creative partnerships.</p><p><strong>Key messages: </strong>The development of newborn screening for new rare disorders can require multiple years of painstaking research and implementation science. Support and cooperation among patient advocacy groups, clinical experts, public health researchers, and government agencies are essential for the successful rollout of new newborn screening tests and follow-up protocols.</p>","PeriodicalId":49650,"journal":{"name":"Public Health Genomics","volume":" ","pages":"83-93"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Public Perspectives on Sharing Profits with Biospecimen Donors.","authors":"Aaron Eli Segal, Xiaobai Li, David Wendler","doi":"10.1159/000549697","DOIUrl":"10.1159/000549697","url":null,"abstract":"<p><strong>Introduction: </strong>In current practice, individuals rarely share in the profits of research using their biospecimens. Many commentators defend this practice on the grounds that the contributions donors make are not important enough to merit a share of the profits. Others argue that if researchers and sponsors profit, donors should too. Despite the importance of this debate, there are no data on the public's views.</p><p><strong>Methods: </strong>Online survey of US adults selected to approximate the 2020 US census on age, gender, race, ethnicity, and geographic region. Respondents were asked whether biospecimen donors should share in the profits or receive payments across six scenarios, differing on whether the research yields a profit and which other parties share in the profits.</p><p><strong>Results: </strong>A total of 77.2% of respondents indicated that donors should share in the profits when researchers profit and 78.9% when sponsors profit. Support for profit sharing was strong across all groups assessed, although respondents who were older, white, and wealthier were less likely to think donors should share in the profits.</p><p><strong>Conclusion: </strong>A significant majority of a sample of the US public thinks individuals who donate their biospecimens should share in the profits of research that uses their samples. These findings offer compelling reason to reconsider current practice of not sharing profits with biospecimen donors.</p>","PeriodicalId":49650,"journal":{"name":"Public Health Genomics","volume":" ","pages":"10-20"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interest in Genetic Testing for Hereditary Cancer Risk: Associations with Genetic Familiarity, Self-Efficacy, and Sociodemographics.","authors":"DaLaina Marie Cameron, Emerson Dusic, Tesla Nikola Theoryn, Faith Beers, Sarah Knerr, Catharine Wang, Deborah Bowen, Elizabeth Swisher","doi":"10.1159/000552069","DOIUrl":"10.1159/000552069","url":null,"abstract":"<p><strong>Introduction: </strong>Genetic testing (GT) for hereditary cancer risk enables early detection and prevention, yet many individuals who could benefit do not pursue testing. Limited genetic familiarity and lower genetic self-efficacy may act as barriers. This study examined relationships among patient-reported genetic familiarity, genetic self-efficacy, sociodemographic characteristics, and interest in GT.</p><p><strong>Methods: </strong>Data were drawn from the Early Detection of Genetic Risk (EDGE) baseline survey (n = 2,319), distributed to a random sample of patients aged ≥25 years from participating primary care clinics in Washington, MT, and WY. Patients were contacted via email and mailed letter in January 2021, prior to implementation of the EDGE intervention. Bivariate logistic regression assessed associations between sociodemographic factors and genetic familiarity and self-efficacy. Multivariable logistic regression examined independent associations between sociodemographic factors, genetic familiarity, genetic self-efficacy, and interest in GT.</p><p><strong>Results: </strong>In multivariable analyses, higher genetic familiarity was strongly associated with interest in GT (adjusted odds ratio [aOR] = 2.67; 95% CI: 1.47-4.86). Higher income (aOR = 2.43; 95% CI: 1.43-4.13) and female sex compared with male (aOR = 1.80; 95% CI: 1.16-2.40) were also positively associated with interest in GT. Participants aged over 65 years were significantly less likely to express interest in GT (aOR = 0.28; 95% CI: 0.13-0.60).</p><p><strong>Conclusion: </strong>The strong association between genetic familiarity and interest in GT suggests that increasing basic genetic knowledge may be an effective starting point for educational interventions aimed at improving testing uptake. Understanding drivers of interest in GT can inform targeted strategies to enhance hereditary cancer prevention and early detection efforts.</p>","PeriodicalId":49650,"journal":{"name":"Public Health Genomics","volume":" ","pages":"149-157"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Reporting and Outreach for Surveillance and Risk-Reducing Surgeries for Cancer Genetic Predisposition: Findings of a Workshop Organized by the International Cascade Consortium.","authors":"Bardha Citaku-Qerimi, Hanna Yttring, Sofia E Andersson, Margreet G E M Ausems, Sivia Barnoy, Maria Caiata-Zufferey, Deborah Cragun, Efrat Dagan, Marleah Dean, Katrina R Ellis, Lea Godino, Senada Hajdarevic, Ylva Heyman, Sue Kim, Fred H Menko, Carla Pedrazzani, Helle V Petersen, Amicia Phillips, Susanna Pusa, Charité N Ricker, Anna Rosén, Meghan Underhill, Pamela Ganschow, Elena M Stoffel, D Gareth Evans, Joanne Ngeow, Tuya Pal, Heather Hampel, Maria C Katapodi","doi":"10.1159/000553075","DOIUrl":"10.1159/000553075","url":null,"abstract":"<p><strong>Introduction: </strong>Improving access to genetic testing has increased the number of individuals identified with cancer genetic predisposition. Hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) are key examples of high-risk hereditary cancer syndromes. Ensuring that carriers of germline pathogenic/likely pathogenic variants (GPVs) receive evidence-based risk counseling, surveillance and risk-reducing interventions remains a global challenge. Variations in implementation and reporting of international guidelines across healthcare systems contribute to this problem.</p><p><strong>Methods: </strong>An international workshop on cancer genetic care, held from March 12 to March 15, 2025, in Switzerland, brought together 40 experts on this topic from 10 countries. The workshop combined evidence-based presentations with expert-led discussions and considered novel strategies, which were synthesized in key discussion points.</p><p><strong>Results: </strong>Participants highlighted major inconsistencies in reporting age of initiation and uptake of surveillance, follow-up intervals, and uptake of risk-reducing interventions for carriers of GPVs associated with genetic predisposition to cancer between and within countries. These differences are due to variations in available technology, insurance coverage, and sociocultural attitudes that shape national clinical guidelines. Participants emphasized the need for a standardized approach for reporting surveillance practices, including clear definitions of gene-specific recommendations, timing of follow-up, and alternatives when ideal resources are limited. In addition to these reporting issues, participants also noted the need for sustained outreach for lifelong follow-up surveillance of GPV carriers through digital as well as low-tech approaches.</p><p><strong>Conclusion: </strong>Standardized reporting of surveillance and risk-reducing practices across countries may improve the quality and comparability of data in cancer genetic predisposition, reveal gaps in genetic care, and inform outreach strategies for engaging GPV carriers in lifelong cancer risk management.</p>","PeriodicalId":49650,"journal":{"name":"Public Health Genomics","volume":" ","pages":"209-217"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13450973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148354284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"I Know that One Day I Will Be Cured\": Perspectives on Acceptability of Curative Therapies for Sickle Cell Disease in Tanzania.","authors":"Daima Bukini, Kassim Kassim, Collins Kanza, Aisha Rifai, Rahma Chanzi, Augostino Amando, Elianna Amin, Jonathan Spector, Julie Makani","doi":"10.1159/000551690","DOIUrl":"10.1159/000551690","url":null,"abstract":"<p><strong>Introduction: </strong>While curative treatments for sickle cell disease (SCD), including hematopoietic stem cell transplant and gene therapies, are largely restricted to high-resource settings, recent advancements have raised hopes that they will eventually become more accessible to patients in Africa, where the disease is particularly prominent and contributes to substantial morbidity and mortality. Understanding the factors that influence acceptability of curative therapies will therefore be important in developing strategies for successful adoption and implementation.</p><p><strong>Methods: </strong>To address this need, a qualitative study was conducted to gain insights into the perspectives of patients and families in Tanzania regarding curative therapies for SCD, focusing on factors affecting treatment acceptability. A total of 81 individuals (46 caregivers and 35 patients) participated in focus group discussions or in-depth interviews; the majority were female (67%) and between 21 and 40 years of age.</p><p><strong>Results: </strong>The results indicated substantial interest in current and prospective curative programs, with various factors influencing the attitudes of patients and caregivers differently. The findings suggested that caregivers' decisions were likely to be influenced by the burden of caregiving roles and the financial costs related to care for SCD. Patients were more likely to accept the therapies if provided with information on safety of the therapies and transparency of data from treated patients.</p><p><strong>Conclusion: </strong>In preparation for GT trials or transplants, tailored engagement strategies for patients younger than 18 years old will be necessary as the majority of SCD patients in Africa are children. Healthcare professionals must be well informed to address questions and concerns from patients' families. Overall, the study highlighted strong interest in curative therapies for SCD in Tanzania while identifying important factors shaping acceptability, underscoring the need for tailored engagement and early involvement of affected families in program planning.</p>","PeriodicalId":49650,"journal":{"name":"Public Health Genomics","volume":" ","pages":"257-268"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148406668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health Literacy and Awareness of Family Health History in the All of Us Research Program.","authors":"Jemar R Bather, Melody S Goodman, Stephanie H Cook, Kimberly A Kaphingst","doi":"10.1159/000550532","DOIUrl":"10.1159/000550532","url":null,"abstract":"<p><strong>Introduction: </strong>A 2016 study showed that limited health literacy was associated with lower awareness of family health history. However, this analysis was conducted among adult patients in St. Louis, Missouri, thereby warranting broader replication.</p><p><strong>Methods: </strong>We quantified the association between health literacy and awareness of family health history using a nationwide cross-sectional study of 286,293 All of Us Research Program participants. Modified Poisson regression models estimated PRs (PRs): model 1 (unadjusted), model 2 (demographic factors), model 3 (socioeconomic status), model 4 (health insurance), model 5 (self-rated health status), and model 6 (number of chronic health conditions).</p><p><strong>Results: </strong>The average age was 53 years (SD = 17), with 4% who self-reported no awareness of family health history and 17% who had limited health literacy. Without controlling for confounders (model 1), participants with limited health literacy were 3.06 (95% confidence interval [CI]: 2.95-3.17) times more likely than those with adequate health literacy to report no awareness of family health history. This significant association persisted but attenuated in models 2 (adjusted PR [aPR]: 2.04, 95% CI: 1.96-2.12) and 3 (aPR: 1.43, 95% CI: 1.37-1.49). The association remained stable in models 4-6 with the sequential addition of health insurance coverage (aPR: 1.42, 95% CI: 1.37-1.48), self-rated health status (aPR: 1.42, 95% CI: 1.36-1.47), and number of chronic health conditions (aPR: 1.42, 95% CI: 1.36-1.48).</p><p><strong>Conclusion: </strong>These findings indicate that increasing health literacy may increase awareness of family health history, which is vital for delivery of personalized healthcare and active patient participation in precision medicine.</p>","PeriodicalId":49650,"journal":{"name":"Public Health Genomics","volume":" ","pages":"1-9"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12923247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent and Young Adult Perspectives on Receiving Pathogenic or Likely Pathogenic Results in a Prospective Genomic Screening Clinical Trial.","authors":"Jessica A Sinclair, Emma C Donigan, Cara L Barnett, Erin M Miller, Melanie F Myers, Michelle L McGowan","doi":"10.1159/000552865","DOIUrl":"10.1159/000552865","url":null,"abstract":"<p><strong>Introduction: </strong>Professional societies recommend pediatric genetic testing only when results may impact medical management in childhood. However, with increasing access to genetic information in various settings, young people's responses to learning pathogenic or likely pathogenic (P/LP) genetic results remain understudied.</p><p><strong>Methods: </strong>The Engaging Adolescents in Decisions about Return of Genomic Research Results clinical trial enrolled 483 adolescents and young adults (ages 13-21 years) who made decisions about whether to undergo prospective genomic screening to learn their personal results related to 32 sets of treatable, preventable, and adult-onset conditions and carrier traits. Participants (n = 15) who received P/LP results were invited to participate in an interview at least 3 months after receiving their results.</p><p><strong>Results: </strong>Eleven individuals (ages 14-19 years) participated in an interview. Most interviewees accurately recalled their P/LP results and reported satisfaction with learning personal genetic information, despite experiencing short-lived anxiety and confusion. While participants had knowledge of relevant risk reduction and screening measures, most viewed their genetic test results as a future consideration. Several participants' family members underwent cascade testing after learning the young person's results. Reactions to or risk-reducing behaviors taken since learning results did not differ between disease categories associated with the result.</p><p><strong>Conclusion: </strong>In support of a growing body of empirical research engaging young people in genetic testing decisions and outcomes, our findings suggest that young people who choose to learn genetic information about themselves understand the implications and potential actionability of P/LP results and actively incorporate results into their and their family members' lives.</p>","PeriodicalId":49650,"journal":{"name":"Public Health Genomics","volume":" ","pages":"171-181"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13367749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148213101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Based Disparities in Fabry Disease Cause Challenges in Newborn Screening.","authors":"Yutaka Furuta, Neena S Agrawal, Natalie N Owen, Lisa A Bastarache, Cathy Shyr, Hanabi U Geiger, Elvira Ponce, Chelsea J Lauderdale, Camille R Carter, Karee A Morgan, Rizwan Hamid, John A Phillips Iii, Rory J Tinker","doi":"10.1159/000552599","DOIUrl":"10.1159/000552599","url":null,"abstract":"<p><strong>Introduction: </strong>Fabry disease (FD) is a multi-systemic, X-linked lysosomal storage disorder caused by decreased α-galactosidase activity. Early diagnosis enables timely treatment, but enzyme-based newborn screening (NBS) may not detect affected females. We hypothesized that enzyme-based NBS limitations contribute to sex-based diagnostic disparities in FD and investigated these differences.</p><p><strong>Methods: </strong>Retrospective cohort analyses used data from the Fabry Registry (FR: 2001-2023) and Tennessee NBS (2017-2024). Sex differences in diagnosis via NBS, biochemical phenotype, symptom onset, and treatment initiation were analyzed using Wilcoxon and chi-square tests.</p><p><strong>Results: </strong>Among 8,657 FR individuals, 73 (67 males, 6 females) were identified via NBS. FR data show that affected females had significantly higher residual α-galactosidase activity than affected males (leukocyte median: 45.9% vs. 3.9%, plasma median: 32.5% vs. 3.9%; p < 0.0001 for both). FR females had delayed symptom onset (18.1 vs. 11.1 years), later diagnosis (35.5 vs. 30.8 years), and lower treatment rates (51.1% vs. 80.8%) compared to males (all %, p < 0.0001). Tennessee NBS detected 25 males but no females.</p><p><strong>Conclusion: </strong>Females with FD have delays in symptom onset, diagnosis, and treatment compared to males. Furthermore, higher residual enzyme activity causes current enzyme-based NBS to miss most females. Incorporating sex-specific cutoffs and/or molecular sequencing into NBS could improve early detection and reduce sex-based disparities.</p>","PeriodicalId":49650,"journal":{"name":"Public Health Genomics","volume":" ","pages":"158-168"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13345605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}