Rare Disease Community Research Articles

Operational description of rare diseases: a reference to improve the recognition and visibility of rare diseases

Improving health and social equity for persons living with a rare disease (PLWRD) is increasingly recognized as a global policy priority. However, there is currently no international alignment on how to define and describe rare diseases. A global reference is needed to establish a mutual understanding to inform a wide range of stakeholders for actions. A multi-stakeholder, global panel of rare disease experts, came together and developed an Operational Description of Rare Diseases. This reference describes which diseases are considered rare, how many persons are affected and why the rare disease population demands specific attention. The operational description of rare diseases is framed in two parts: a core definition of rare diseases, complemented by a descriptive framework of rare diseases. The core definition includes parameters that permit the identification of which diseases are considered rare, and how many persons are affected. The descriptive framework elaborates on the impact and burden of rare diseases on patients, their caregivers and families, healthcare systems, and society overall. The Operational Description of Rare Diseases establishes a common point of reference for decision-makers across the world who strive to understand and address the unmet needs of persons living with a rare disease. Adoption of this reference is essential to improving the visibility of rare conditions in health systems across the world. Greater recognition of the burden of rare diseases will motivate new actions and policies to address the unmet needs of the rare disease community.

An Inventory of Rare Disease Registries in the Canadian Landscape

What Was the Question? There is a lack of centralized information about rare disease registries (RDRs) in Canada. To address this, we created an inventory of RDRs in Canada and international RDRs that include patients living in Canada. What Did We Do? Information about RDRs was identified through a search of published literature, grey literature, consultations with members of the rare disease community, and a survey with the registry holders. What Did We Find? We identified 148 RDRs, of which 66 are RDRs in Canada and 82 international RDRs. In total, 21% of RDRs in Canada and 11% of international RDRs capture rare cancer(s). About a half of RDRs in Canada (53%) and international RDRs (46%) collaborate with other national or international registries or networks. Most RDRs in Canada (73%) and international RDRs (86%) identify patients for RDR enrollment through health care provider referrals. Electronic medical records (68%), clinician-reported data (68%), and medical chart abstraction (60%) are the most common sources of data for RDRs in Canada compared to international RDRs, for which patient (79%) and caregiver (61%) surveys are most common. Most RDRs in Canada collect clinical data (95%), laboratory and diagnostic data (85%), health outcomes data (83%), and treatment data (78%), and less commonly patient-generated data (55%) and caregiver data (15%). What Does This Mean? The information in the inventory will help guide future initiatives for improving the RDR landscape in Canada. Most RDRs in Canada source data from electronic health records, clinician-reported data, and medical charts. Fewer RDRs in Canada implement patient and caregiver surveys. RDRs in Canada include information relevant to decision-makers as most collect clinical data, health outcomes data, and treatment data, and about half collect health resource utilization data. This inventory will support future initiatives to assess the suitability of RDRs for generating decision-grade real-world evidence.

Framing the European Rare Diseases field through a structured movement of patient organisations

EURORDIS-Rare Diseases Europe is an alliance of patient organisations, working across countries, empowering patients with trainings, and generating evidence through surveys. It advocates for the needs of people living with rare diseases in Europe, influencing policy, legislation, research, healthcare services, social inclusion, medicines development and access. Since its creation, EURORDIS has maintained a global perspective. By nature of the rarity of these conditions, knowledge and expertise are scattered, so collaboration on a global level is required to have an understanding of disease progression. Thus, every rare disease patient group must be equipped to collaborate beyond its own borders. EURORDIS impacts global activities with a focus on raising awareness; empowering a global alliance; supporting international, national and regional initiatives; and recognising rare diseases within the international community while fostering collaboration among stakeholders. For these reasons, the organisation’s impact extends beyond Europe, as demonstrated by its international partnerships. This perspective paper explores EURORDIS’ achievements over two decades, examining its role in shaping policies and regulations, to demonstrate the vital importance of global collaboration in the rare disease field. Looking ahead, EURORDIS’ Strategic Goals, to be achieved by 2030, align with the United Nations Sustainable Development Goals Agenda 2030 and advocate for a European Action Plan for Rare Diseases. This illustrates EURORDIS’ continued commitment to transforming policies into tangible outcomes. With its ongoing dedication, collaborative efforts, and enduring impact on the rare disease community, EURORDIS remains a driving force for positive change in the lives of people living with rare diseases.

Development of orphan drugs for rare diseases.

Most rare diseases (orphan diseases) still lack approved treatment options despite major advances in research providing the necessary tools to understand their molecular basis and legislation providing regulatory and economic incentives to expedite the development of specific therapies. Addressing this translational gap is a multifaceted challenge, a key aspect of which is the selection of an optimal therapeutic modality to translate advances in rare disease knowledge to potential medicines known as orphan drugs. There are several strategies for developing orphan drugs for rare genetic disorders, including protein replacement therapies, small-molecule therapies (e.g., substrate reduction, chemical chaperone, cofactor, expression modification, and read-through therapies), monoclonal antibodies, antisense oligonucleotides, small interfering RNA or exon skipping therapies, gene replacement and direct genome-editing therapies, mRNA therapy, cell therapy, and drug repurposing. Each strategy has its own strengths and limitations in orphan drug development. Furthermore, numerous hurdles are present in clinical trials of rare genetic diseases because of difficulty with patient recruitment, unknown molecular physiology, the natural history of the disease, ethical concerns regarding pediatric patients, and regulatory challenges. To address these barriers, the rare genetic diseases community, including academic institutions, industry, patient advocacy groups, foundations, payers, and government regulatory and research organizations, must become engaged in discussions about these issues.

Intellectual disability: A potentially treatable condition.

The application of genomics has greatly increased the diagnosis of specific monogenic causes of intellectual disability and improved our understanding of the neuronal processes that result in cognitive impairment. Meanwhile, families are building rare disease communities and seeking disease-specific treatments to change the trajectory of health and developmental outcomes for their children. To date, treatments for intellectual disability have focussed on metabolic disorders, where early treatment has improved cognition and neurodevelopmental outcomes. In this article, we discuss the treatment strategies that may be possible to change the neurodevelopmental outcome in a broader range of genetic forms of intellectual disability. These strategies include substrate modification, enzyme replacement therapy, gene therapy and molecular therapies. We argue that intellectual disability should now be considered a potentially treatable condition and a strong candidate for precision medicine.

Exploring the role of digital tools in rare disease management: An interview-based study.

While digital tools, such as the Internet, smartphones, and social media, are an important part of modern society, little is known about the specific role they play in the healthcare management of individuals and caregivers affected by rare disease. Collectively, rare diseases directly affect up to 10% of the global population, suggesting that a significant number of individuals might benefit from the use of digital tools. The purpose of this qualitative interview-based study was to explore: (a) the ways in which digital tools help the rare disease community; (b) the healthcare gaps not addressed by current digital tools; and (c) recommended digital tool features. Individuals and caregivers affected by rare disease who were comfortable using a smartphone and at least 18 years old were eligible to participate. We recruited from rare disease organizations using purposive sampling in order to achieve a diverse and information rich sample. Interviews took place over Zoom and reflexive thematic analysis was utilized to conceptualize themes. Eight semistructured interviews took place with four individuals and four caregivers. Three themes were conceptualized which elucidated key aspects of how digital tools were utilized in disease management: (1) digital tools should lessen the burden of managing a rare disease condition; (2) digital tools should foster community building and promote trust; and (3) digital tools should provide trusted and personalized information to understand the condition and what the future may hold. These results suggest that digital tools play a central role in the lives of individuals with rare disease and their caregivers. Digital tools that centralize trustworthy information, and that bring the relevant community together to interact and promote trust are needed. Genetic counselors can consider these ideal attributes of digital tools when providing resources to individuals and caretakers of rare disease.

“We are always in self-isolation”: Navigating COVID-19 as a young person in Canada with cystic fibrosis

The pandemic disproportionately influenced marginalized communities in North America. However, the social and spatial inequalities impacting marginalized rare genetic disease communities – such as those living with cystic fibrosis – have not been heard in mainstream pandemic narratives. Sensitized by the social determinants of health, this qualitative study explored the experiences of 12 youth with Cystic Fibrosis (CF) during the pandemic. Content analysis revealed four themes. Youth with CF experienced changes across physical spaces, faced pandemic anxiety, and struggled with access to digital and medical spaces. Youth also reflected on being “used to” life-long physical distancing as a result of CF. Our findings show the complexity of environments for youth with CF during the pandemic while demonstrating how Covid-19 shaped the lives of rare disease communities. Our findings also illustrate spatial and social inequities among marginalized, rare genetic disease communities.

Needs and Experiences With Health Care Providers of Adult Rare Disease Patients and Caregivers of People With Rare Diseases: Protocol for a Qualitative Study.

Rare diseases in Europe are defined as diseases with a prevalence of less than 5 per 10,000 people. Despite their individual rarity, the total number of rare diseases is considerable. Rare diseases are often chronic and complex, affecting physical, mental, and neurological health. People with rare diseases face challenges such as delayed diagnosis, limited medical support, and financial burden. Caregivers, usually family members, bear significant physical and emotional burdens. Understanding the experiences of patients with rare disease and their caregivers is critical to effective care, but this is still underresearched. Better support and understanding of the challenges faced by both patients and caregivers is clearly needed. Our study will explore the experiences and needs of people with rare diseases and caregivers of people with rare diseases in relation to accessing health services. This study aims to explore the experiences of patients with rare disease and their caregivers with Slovenian health care providers and to create a theoretical model of needs and experiences. This is a qualitative thematic analysis study, using the codebook approach. The study will conduct semi-open-ended interviews to understand the experiences and needs of people with rare diseases and caregivers of people with rare diseases in relation to accessing health services. The interview questions will be based on an extensive literature review. Data from the interviews will be analyzed using thematic analysis to identify patterns and build a thematic map. Data will be analyzed by at least 2 coders. To ensure reliability, respondent validation will be conducted and negative cases investigated. Any discrepancies will be resolved by consulting the entire research team until a consensus is reached. This study was not specifically funded. However, author TČ is supported by grant number P3-0339 from the Slovenian Agency for Research and Innovation. This study was approved by the Medical Ethics Committee of the Republic of Slovenia (0120-47/2022/3), and recruitment is expected to begin in May 2024, with data analysis results anticipated by the end of 2025. This study will fill an important research gap in Slovenia by exploring the needs and experiences of people living with rare diseases and their caregivers. The results will contribute to the broader field of rare diseases and add knowledge that can inform future research processes and intervention strategies. It also aims to identify neglected areas that have a significant impact on the lives of people with rare diseases. This study is important not only because it addresses the immediate needs of the Slovenian rare disease community, but also because it contributes to a discussion on patient-centered care, health policy design, and the inclusion of psychosocial components in health care. PRR1-10.2196/53362.

Designing an accessible and equitable conference and the evaluation of the barriers to research inclusion for rare disease communities

Introduction: The United Kingdom Rare Diseases Framework, published in 2021, addresses the lack of diversity in rare disease research, particularly in clinical trials, due to intersecting issues related to rare disease symptoms and health inequalities. The framework outlines the government's commitment to improving the lives of the 3.5 million people living with rare conditions in the United Kingdom.Objective: The primary objective is to advance equality, diversity, and inclusion in research by developing innovative methods to engage with communities, establish trust, and enhance the participation and voices of underrepresented and underserved communities.Methods: The conference was held in May 2023, bringing together voices with lived experiences from rare and diverse communities to meet and discuss with established researchers, policy influencers and advocates. The evaluation design was developed using the Program Logic Model and utilised a conference evaluation form on barriers to inclusion.Results: The Rare Disease Community identifies disability as the primary obstacle to inclusion. Social Care and Public Health Communities and Clinical Research Communities identified a need for more cultural competency. The Diverse Community selected psychosocial issues, and the Academic Community identified funding as the most significant barrier.Conclusions: The Community of Practice workshops showed the variety of lived experiences and potential barriers people confront for inclusion in research. Listening to individual viewpoints was crucial to creating or repairing community trust. The Academic Community felt that research funders and ethics review boards must adapt their institutional practices to include financial resources for outreach and participation in research design.

Paradox of possibilities: the rare landscape in the Asia Pacific Region

The Asia-Pacific (APAC) region, home to 60% of the global population, has the highest number of Persons Living with a rare disease (PLWRD). To promote more equitable societies, the Asia Pacific rare disease Organization (APARDO), established in 2015, has been developing its regional position to promote collaboration, increase awareness among stakeholders, explore equitable and affordable diagnosis and treatment, and improve health outcomes and quality of life for all PLWRD. The APAC region’s heterogeneous population and complex healthcare environment pose distinctive challenges in addressing rare diseases. Through conferences, webinars, and contributions to global initiatives, APARDO is fostering connectivity and providing a platform as a part of the global rare disease (RD) community to address shared challenges. The development of APARDO to strengthen its global presence as the representative of the APAC RD region is vital for a more equitable world.

ERCAL, a regional initiative for rare diseases in Latin America and the Caribbean

The importance of establishing programs to address the challenges of patients living with rare diseases has been recognized internationally, yet many countries, especially in low- and middle-income regions, are lagging in the recognition of the challenges and needs of patients and families. To improve this situation, the Enfermedades Raras en el Caribe y America Latina (ERCAL) initiative was established in 2020 with the vision of bringing together patients, patient representatives, organizations, researchers, clinicians, regulators, and all interested stakeholders in the rare diseases ecosystem under a common collaborative platform to sum efforts to improve the lives of patients and families living with rare diseases in the Latin American and the Caribbean region. Over the last three years, we have been working consistently to establish an agenda of priorities and objectives to guide the work of the initiative and address the major challenges faced by the rare disease community in the region.

Collaborative research in myositis-related disorders: MIHRA, a global shared community model.

Myositis International Health and Research Collaborative Alliance (MIHRA) is a newly formed purpose-built non-profit charitable research organization dedicated to accelerating international clinical trial readiness, global professional and lay education, career development and rare disease advocacy in IIM-related disorders. In its long form, the name expresses the community's scope of engagement and intent. In its abbreviation, MIHRA, conveys linguistic roots across many languages, that reflects the IIM community's spirit with meanings such as kindness, community, goodness, and peace. MIHRA unites the global multi-disciplinary community of adult and pediatric healthcare professionals, researchers, patient advisors and networks focused on conducting research in and providing care for pediatric and adult IIM-related disorders to ultimately find a cure. MIHRA serves as a resourced platform for collaborative efforts in investigator-initiated projects, consensus guidelines for IIM assessment and treatment, and IIM-specific career development through connecting research networks.MIHRA's infrastructure, mission, programming and operations are designed to address challenges unique to rare disease communities and aspires to contribute toward transformative models of rare disease research such as global expansion and inclusivity, utilization of community resources, streamlining ethics and data-sharing policies to facilitate collaborative research. Herein, summarises MIHRA operational cores, missions, vision, programming and provision of community resources to sustain, accelerate and grow global collaborative research in myositis-related disorders.

Developing a community-led rare disease ELSI research agenda.

Research priorities are best defined through engagement with communities who will be impacted by the research and have lived experience of the topics to be studied. We aimed to establish a pediatric rare disease community stakeholder group and empower them in (1) eliciting perspectives from affected families in the wider region and (2) synthesizing collective ideas into a research agenda focused on shared ethical, legal, and social implications (ELSI) across rare disease. This two-year project utilized a community-centered approach to engage rare disease community members as equal partners in developing a research agenda for ELSI in rare disease. We established "Rare Voices" (RV), a 22-member stakeholder group of patients, parents, clinicians and researchers. Following capacity-building trainings, RV designed and conducted listening sessions with teen patients and parents of children with rare diseases to explore challenges, positive experiences, and ethical concerns. Listening session findings were synthesized and contextualized into research topics, which RV members further refined and prioritized. We used established measures to assess RV member engagement and satisfaction. From 14 listening sessions with parents (n = 52) and teen patients (n = 13), RV identified eight core research topics as most important for future rare disease research: coordinating care, communication, accessing resources and care, impact on family unit, community and support in society, mental health and identity, ethical aspects of care, and uncertainty. RV members were highly engaged throughout the two-year project and reported high levels of satisfaction with the experience and research agenda. Through capacity-building and authentic engagement, this project resulted in a community-led rare disease research agenda to guide future rare disease ELSI research that aligns with patients' and families' priorities. An environment of equal partnership and respect created a space for mutual learning where community members were empowered to shape the research agenda based on their collective experiences. The agenda recognizes the shared psychosocial and healthcare experiences of rare disease and offers practical areas of research to address patient and family needs.

Drug repurposing for rare: progress and opportunities for the rare disease community.

Repurposing is one of the key opportunities to address the unmet rare diseases therapeutic need. Based on cases of drug repurposing in small population conditions, and previous work in drug repurposing, we analyzed the most important lessons learned, such as the sharing of clinical observations, reaching out to regulatory scientific advice at an early stage, and public-private collaboration. In addition, current upcoming trends in the field of drug repurposing in rare diseases were analyzed, including the role these trends could play in the rare diseases' ecosystem. Specifically, we cover the opportunities of innovation platforms, the use of real-world data, the use of artificial intelligence, regulatory initiatives in repurposing, and patient engagement throughout the repurposing project. The outcomes from these emerging activities will help progress the field of drug repurposing for the benefit of patients, public health and medicines development.

The Use of Social Media to Express and Manage Medical Uncertainty in Dyskeratosis Congenita: Content Analysis.

Social media has the potential to provide social support for rare disease communities; however, little is known about the use of social media for the expression of medical uncertainty, a common feature of rare diseases. This study aims to evaluate the expression of medical uncertainty on social media in the context of dyskeratosis congenita, a rare cancer-prone inherited bone marrow failure and telomere biology disorder (TBD). We performed a content analysis of uncertainty-related posts on Facebook and Twitter managed by Team Telomere, a patient advocacy group for this rare disease. We assessed the frequency of uncertainty-related posts, uncertainty sources, issues, and management and associations between uncertainty and social support. Across all TBD social media platforms, 45.98% (1269/2760) of posts were uncertainty related. Uncertainty-related posts authored by Team Telomere on Twitter focused on scientific (306/434, 70.5%) or personal (230/434, 53%) issues and reflected uncertainty arising from probability, ambiguity, or complexity. Uncertainty-related posts in conversations among patients and caregivers in the Facebook community group focused on scientific (429/511, 84%), personal (157/511, 30.7%), and practical (114/511, 22.3%) issues, many of which were related to prognostic unknowns. Both platforms suggested uncertainty management strategies that focused on information sharing and community building. Posts reflecting response-focused uncertainty management strategies (eg, emotional regulation) were more frequent on Twitter compared with the Facebook community group (χ21=3.9; P=.05), whereas posts reflecting uncertainty-focused management strategies (eg, ordering information) were more frequent in the Facebook community group compared with Twitter (χ21=55.1; P<.001). In the Facebook community group, only 36% (184/511) of members created posts during the study period, and those who created posts did so with a low frequency (median 3, IQR 1-7 posts). Analysis of post creator characteristics suggested that most users of TBD social media are White, female, and parents of patients with dyskeratosis congenita. Although uncertainty is a pervasive and multifactorial issue in TBDs, our findings suggest that the discussion of medical uncertainty on TBD social media is largely limited to brief exchanges about scientific, personal, or practical issues rather than ongoing supportive conversation. The nature of uncertainty-related conversations also varied by user group: patients and caregivers used social media primarily to discuss scientific uncertainties (eg, regarding prognosis), form social connections, or exchange advice on accessing and organizing medical care, whereas Team Telomere used social media to express scientific and personal issues of uncertainty and to address the emotional impact of uncertainty. The higher involvement of female parents on TBD social media suggests a potentially greater burden of uncertainty management among mothers compared with other groups. Further research is needed to understand the dynamics of social media engagement to manage medical uncertainty in the TBD community.

A unique collaborative model providing supportive and self-advocacy tools to the rare disease community

The National Ehlers-Danlos Syndromes (EDS) service is a highly specialised NHS commissioned service for diagnosing and supporting people with a rare, monogenic type of EDS. The service consists of a team of medical specialists and genetic counsellors. The EDS service has strong ties with national and international EDS charities, and together they participate in working and strategy groups alongside patients and carers. Acquired funding for research means that the service contributes to international knowledge regarding diagnosis and management of rare, monogenic EDS types. As a result of being a highly specialised service, there are multiple points of contact with patients, providing frequent opportunities for feedback. Patient data, surveys and collaborative working have enabled the development not only of extensive information resources and self-advocacy tools for patients, but also guidelines for health care professionals on the best ways to support their rare disease patients. The main challenges faced by patients affected by rare disease and the importance of self-advocacy are discussed, with the highly specialised National EDS service and the patients seen in this service as an example. The recommendations from this unique collaborative model include eight specific domains of self-advocacy: increasing knowledge of rare disease, taking care of mental well-being, taking care of physical well-being including routine care, the development of good working relationships between patients and health care professionals, information accessibility, emergency preparedness, taking part in education and outreach, and involvement in research and feedback opportunities. The service aims to be an example of patient-centred innovation and progress, providing a patient-focused supportive model that can be adapted by the rare disease community and other health care professionals.

Health services interventions to improve the quality of care in rare disease: a scoping review

Background: Rare diseases are often complex, multisystem disorders requiring specialized, lifelong care. These diseases share significant challenges in healthcare delivery, including diagnostic delays, limited access to specialists, and lack of effective treatments. Objectives: To aggregate and critically examine innovative health services interventions for rare diseases, with the goal of identifying potentially scalable strategies to improve care. Eligibility criteria: Peer-reviewed original research published in English reporting results of interventions to improve guideline-concordant care, care coordination, and care transitions in rare disease populations. Using Covidence software, two researchers independently screened all texts against preestablished inclusion and exclusion criteria, with conflicts resolved through consensus discussion with a third researcher. Sources of evidence: Comprehensive searches were conducted in April 2022 in Ovid MEDLINE, Embase.com, Web of Science Core Collection, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov. Charting methods: Two researchers independently extracted study characteristics and results from eligible full texts using Covidence software, with any conflicts resolved through consensus discussion with a third researcher. Results: Our search identified 2899 articles. After screening for eligibility criteria, 12 articles describing health services interventions in rare diseases were identified. Most studies were conducted in Europe and involved adult participants. Three main intervention targets were identified: (1) increasing patients’ access to multidisciplinary expertise (e.g. using expert panels/tumor boards, integrating additional disciplines into care teams, and creating a hotline for specialist advice); (2) using technology to give point-of-care physicians access to information (e.g. electronic medical record templates/decision-support); and (3) standardizing care through clinical care pathways. Conclusion: This review identified several efficacious interventions to improve healthcare delivery for individuals with a single rare disease. Testing these strategies across broader groups of rare disease patients could more efficiently improve healthcare delivery for the rare disease community, facilitating patients’ timely access to treatments, improving their health outcomes, and potentially reducing healthcare costs with economies of scale.

The advantages of rare disease biobanking: A localised source of genetic knowledge to benefit the South African rare disease community and related stakeholders worldwide

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Understanding the Physical and Psychosocial Impacts of Pyruvate Kinase Deficiency: Patient-Led Development of the Pyruvate Kinase Deficiency Life Phase Model

Background: Pyruvate Kinase (PK) deficiency is a rare congenital hemolytic anemia with an estimated prevalence of 3.2 to 8.5 cases per million in Western populations. Although research is limited, PK deficiency has a wide-ranging impact on quality of life (QoL) physically and psychosocially. Patients often feel that information in these domains in not adequately captured nor the interconnections between them understood during different life phases. To address this gap, the PK Deficiency Advocacy Advisory Council (AAC; formed and funded by Agios Pharmaceuticals), a multi-disciplinary group of patients, carers, advocates, and health care providers (HCPs), developed the PK Deficiency Life Phase Model that summarizes the physical and psychosocial symptoms individuals and their carers may face at specific life phases. Objective: Provide HCPs, patients, and carers a guiding source of information to further understand the potential physical and psychosocial impacts of PK deficiency through a life phase model based on the lived experience of patients and carers. Methods: Life phases were based on published literatureand AAC input (N=2 HCPs, N=4 patients, N=1 advocate and N=1 carer). Lived experiences were collected in AAC workshops and sorted into either physical or psychosocial domains/ themes and assigned to specific life phase(s). The impact of each experience on patients in each life phase was scored on a high to low frequency scale based on AAC experiences. This content formed the Life Phase Model which was verified through several subsequent patient advocacy research steps. A targeted literature review of physical and psychosocial topics was also conducted to refine the model, which was further supplemented with data from Agios' Peak Registry. The Model was pressure tested in three focus groups representing young adult patients aged 18 to 25 (N=9), mature patients aged over 25 (N=14), or carers (N=7) from nine countries. Additional input was collected in in-depth interviews (N=4). Research was conducted in accordance with British Healthcare Business Intelligence Association Legal and Ethical Guidelines, as well as guidelines established by UK Market Research Society. These steps were taken to ensure diversity, accuracy, and inclusivity of experiences from the whole community. Results: Physical themes associated with each life phase included symptoms, complications/comorbidities, impacts of transfusions, iron overload and disease management options. Psychological themes included disease impact on mental health and psychological wellbeing, family dynamics, aging, school and work, symptom impact on daily life, and the future. Most supportive literature was relevant to physical domains (N=18); few reports were available to support the psychological themes (N=9). These themes were used to develop a PK Deficiency Life Phase Model (Figure). Information from the literature, AAC patient and carers members, and focus group participants were used to determine the degree of impact or burden of each physical and psychological theme at each life stage. Higher impact was depicted with a darker shade in the model. The resulting model provides a well-grounded snapshot of the implications of living with PK deficiency and patient/carer perspective of how each category affects the individual patient population. For most physical and psychological themes, frequency tends to increase with age. For example, the impact of disease symptoms was most severe for young adults, adults, and older adults. Complications and comorbidities associated with PK deficiency appear to affect individuals of all ages similarly. The impact of the disease on mental health increases with age. Adolescents struggled with challenges associated with growing up with a chronic condition. All age groups noticed the impact of PK deficiency on school, work, and/or hobbies. Conclusions: The PK Deficiency Life Phase Model captures the psychological and physical burden of disease from the literature and directly from patients and carers. Hematologists can use this model to better understand how the spectrum of disease burden impacts patients and carers over time, further serving as a source of information for patients, carers, and healthcare professionals that support this rare disease community. Future research efforts can build on this qualitative work to further understand PK Deficiency patient experience over time.

DECIPHER: Improving Genetic Diagnosis Through Dynamic Integration of Genomic and Clinical Data.

DECIPHER (Database of Genomic Variation and Phenotype in Humans Using Ensembl Resources) shares candidate diagnostic variants and phenotypic data from patients with genetic disorders to facilitate research and improve the diagnosis, management, and therapy of rare diseases. The platform sits at the boundary between genomic research and the clinical community. DECIPHER aims to ensure that the most up-to-date data are made rapidly available within its interpretation interfaces to improve clinical care. Newly integrated cardiac case-control data that provide evidence of gene-disease associations and inform variant interpretation exemplify this mission. New research resources are presented in a format optimized for use by a broad range of professionals supporting the delivery of genomic medicine. The interfaces within DECIPHER integrate and contextualize variant and phenotypic data, helping to determine a robust clinico-molecular diagnosis for rare-disease patients, which combines both variant classification and clinical fit. DECIPHER supports discovery research, connecting individuals within the rare-disease community to pursue hypothesis-driven research.