Knowledge Of Rare Disease Research Articles

Building a National Policy for Rare Disease in Brazil.

Rare diseases (RD) are individually rare, although encompass a significant proportion of the population, affecting not only the individuals but also their families. In Brazil RD is defined by the Ministry of Health as a disorder that affects up to 65 individuals in 100,000, or 1.3 individuals in every 2,000. In this review the environment that led to the publication of a National Policy for Comprehensive Care for People of Rare Disease in 2014, a national plan with the aim to decrease morbidity and mortality of RD, improving the care of people with RD in the public health system are described. The process that finally led to such policy took over a decade, moving forward not only due to technical needs, but having patient organizations as essential actors and advocates. Specialized centers in RD were licensed and, since its publication, 33 centers have been accredited; such process, however, has been slow and concentrated in specific regions and larger cities of the country. Despite the incorporation of genetic tests in 2014 and exome sequencing later in 2020, many genetic tests are not offered by specialized centers, with unequal availability across the country. Public health system in Brazil uses ICD-10 for disease coding, preventing appropriate epidemiologic knowledge of RD in Brazil. Incorporation of new technologies as orphan drugs has been in place and regulation for expedite licensing for new RD drugs were issued, although high cost and availability to RD population has been a challenge.

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.

AutoRD: An Automatic and End-to-End System for Rare Disease Knowledge Graph Construction Based on Ontology-enhanced Large Language Models (Preprint)

AutoRD: An Automatic and End-to-End System for Rare Disease Knowledge Graph Construction Based on Ontology-enhanced Large Language Models (Preprint)

Demystifying primary bone leiomyosarcoma: A case study and literature overview

Primary leiomyosarcoma of the bone (LMSB). It's indeed an extremely rare and challenging condition, and case reports like the one you mentioned are valuable in increasing awareness and understanding among clinicians and researchers. LMSB is a subtype of leiomyosarcoma that originates in the bone, specifically the primary bone tissue, and it's distinct from more common bone tumors like osteosarcoma or chondrosarcoma. Given its rarity, diagnosing and treating LMSB can be quite complex, and histopathological examination is often essential to confirm the diagnosis. Treatment options for LMSB are generally limited, and the approach may involve a combination of surgery, radiation therapy, and chemotherapy, although the optimal treatment strategy may vary from case to case. The prognosis for LMSB is generally poor, but early diagnosis and timely intervention can make a difference in patient outcomes. Case reports like the one you mentioned are essential for improving our knowledge of rare diseases like LMSB. They can help clinicians and researchers better understand the condition, its clinical features, and potential treatment strategies. Sharing such cases within the medical community can lead to the development of more effective diagnostic and treatment approaches and potentially improve the prognosis for affected individuals in the future.

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.

Informing a national rare disease registry strategy in Australia: a mixed methods study

BackgroundRare disease registries (RDRs) facilitate monitoring of rare diseases by pooling small datasets to increase clinical and epidemiological knowledge of rare diseases and promote patient centred best practice. The aim of this study was to understand the current state of RDRs in Australia, data captured, impact on patient outcomes, funding models, and barriers and enablers regarding their establishment and maintenance.MethodsAn exploratory sequential mixed methods study design was adopted. First, a list of Australian RDRs, primary contacts and data custodians was generated through online and consumer group (Rare Voices Australia (RVA)) contacts. A cross-sectional, anonymous online survey was distributed to registry custodians, managers, or principal investigators of 74 identified Australian RDRs, 88 RVA Partners, 17 pharmaceutical organizations and 12 RVA Scientific and Medical Advisory Committee members. Next, managers and coordinators of RDRs and databases who participated in the survey were invited to participate in semi-structured interviews. Quantitative and qualitative data were analysed using basic descriptive statistics and content analysis, respectively.ResultsForty RDRs responded to the survey; nine were national, five were based in Australia and New Zealand, and the remaining were global. Of the 40 survey respondents, eight were interviewed. Most of the RDRs captured similar information regarding patient characteristics, comorbidities and clinical features, diagnosis, family history, genetic testing, procedures or treatment types, response to treatments and complications of treatments. Better treatment outcomes, changes in process of care and changes in quality of care were the most frequently reported benefits of the RDRs. The main challenges proved to be cost/funding of data collection, data completeness, and patient consent. When asked, the participants identified opportunities and challenges regarding potential options to streamline RDRs in Australia in the future.ConclusionFindings from this study highlighted significant dataset heterogeneity based on the individual disease, and current lack of interoperability and coordination between different existing RDRs in Australia. Nevertheless, a nationally coordinated approach to RDRs should be investigated given the particular benefits RDRs offer, such as access to research and the monitoring of new disease-modifying treatments.

Knowledge and Awareness of Rare Diseases Among Healthcare Professionals in the Kingdom of Bahrain.

Aim Recent studies highlighted that lack of knowledge on rare diseases is a problem that requires attention. This study aims to assess healthcare professionals' general awareness and knowledge of rare diseases in a tertiary hospital in the Kingdom of Bahrain. Method The study employed a cross-sectional design, utilizing a survey questionnaire derived from the most recent literature. The survey encompassed socio-demographic factors and quiz-based questions that were previously created by Domaradzi and Walkowiak to assess knowledge and awareness of rare diseases. To ensure convenience and accessibility, the survey was made available in both Arabic and English languages. Results Of a total of 333 responses, 25.2% were physicians, 53.8% were nurses, and 21.0% were allied health personnel. The majority of participants (87.4%) were aware of and had heard the term "rare diseases" prior to this survey. Participants were able to recognize what age group is frequently affected by rare diseases (p=0.023) and what the common cause of rare diseases worldwide is (p<0.001). Overall scores showed that only four participants answered all questions correctly, testing their knowledge of rare diseases. There was a weak correlation between self-declared knowledge and the overall score achieved (r=0.190; p<0.001), which indicates that the population's self-declared knowledge did not portray their actual knowledge of rare diseases. Conclusion This study highlights the need for improved knowledge of rare diseases among healthcare professionals, which aligns with the global knowledge landscape. To bridge the knowledge gap, we recommend action plans to ensure that healthcare professionals have rich knowledge of rare diseases and further improve patient care. Additionally, enhancing advocacy efforts is crucial to ensure optimal local and global patient care services.

KNOWLEDGE AND SKILLS OF NURSES REGARDING ORPHAN DISEASES

Introduction. The role of the nurse in providing comprehensive and individualized care to patients with rare diseases is one ofthe key roles. Nurses work closely with physicians and patients and play an educational role for patients and their families, facilitating coordination, monitoring and continuity of care. Therefore, nurses should have a certain range of knowledge and skills regarding the most common rare diseases.The aim of research was to determine the knowledge and skills of nurses regarding some specifi c rare diseases.Material and methods. An anonymous and voluntary survey of nurses was conducted at the regional children’s clinical hospitalfrom April to May 2023. A total of 63 nurses from the hospital participated in the survey. The questionnaire consisted of 27 questions related to the sociodemographic data of the respondents and rare diseases. The most common rare diseases encountered in the practice of nurses at the hospital were primary immunodefi ciencies (PID), spina bifi da (SB), cystic fi brosis, and juvenile idiopathic arthritis.The research results are presented in the form of descriptive statistics. Comparisons of frequency parameters were made using the Chi-square test. Diff erences between parameters were considered statistically signifi cant at p&lt;0.05. Statistical analysis of the survey results was performed using the statistical package STATISTICA 10.0 and Microsoft Excel 2003 spreadsheet editor.The research and the publication of the materials were approved by the Bioethics Committee of the I. Horbachevsky Ternopil National Medical University (protocol № 73 dated 03.04.2023).The study was conducted within the framework of the research project of the Department of Children’s Diseases with PediatricSurgery of the I. Horbachevsky Ternopil National Medical University “Improvement of methods of diagnostics, treatment and rehabilitation of the most common children’s diseases”, registration number 0122U000039.Results. The majority of respondents were female (96.8%), between the ages of 31 and 50 (63.5%), and employed in the hospitalsetting (90.5%). Most were experienced workers with more than 20 years of experience (52.4%). Overall, the majority of respondents (71.0%) correctly identifi ed which diseases are rare. The percentage of correct answers regarding knowledge of rare diseases ranged from 47.9% for PID to 77.5% for SB, while correct answers regarding skills ranged from 41.3% for SB to 63.0% for PID. Overall, nurses demonstrated better knowledge than skills regarding rare diseases (p=0.0003). The most problematic issues were that HIV/AIDS was classifi ed as PID (31.7%), lack of knowledge about standards of neurogenic bladder control in children with SB (49.2%), unfamiliarity with the technique of subcutaneous immunoglobulin administration (87.3%), and bowel cleansing procedures in children with SB (95.2%), as well as infection control in patients with cystic fi brosis (66.1%).Conclusion. The study revealed a lack of awareness among nurses regarding certain rare diseases. The lowest level of knowledge was found for primary immunodefi ciencies. There is a need to improve nurses’ knowledge and skills regarding rare diseases, which can improve the quality of care for rare disease patients and their families. The development of educational interventions for nurses can help to increase their awareness of rare diseases.

RDKG-115: Assisting drug repurposing and discovery for rare diseases by trimodal knowledge graph embedding

Rare diseases (RDs) may affect individuals in small numbers, but they have a significant impact on a global scale. Accurate diagnosis of RDs is challenging, and there is a severe lack of drugs available for treatment. Pharmaceutical companies have shown a preference for drug repurposing from existing drugs developed for other diseases due to the high investment, high risk, and long cycle involved in RD drug development. Compared to traditional approaches, knowledge graph embedding (KGE) based methods are more efficient and convenient, as they treat drug repurposing as a link prediction task. KGE models allow for the enrichment of existing knowledge by incorporating multimodal information from various sources. In this study, we constructed RDKG-115, a rare disease knowledge graph involving 115 RDs, composed of 35,643 entities, 25 relations, and 5,539,839 refined triplets, based on 372,384 high-quality literature and 4 biomedical datasets: DRKG, Pathway Commons, PharmKG, and PMapp. Subsequently, we developed a trimodal KGE model containing structure, category, and description embeddings using reverse-hyperplane projection. We utilized this model to infer 4199 reliable new inferred triplets from RDKG-115. Finally, we calculated potential drugs and small molecules for each of the 115 RDs, taking multiple sclerosis as a case study. This study provides a paradigm for large-scale screening of drug repurposing and discovery for RDs, which will speed up the drug development process and ultimately benefit patients with RDs. The source code and data are available at https://github.com/ZhuChaoY/RDKG-115.

RDBridge: a knowledge graph of rare diseases based on large-scale text mining.

Despite low prevalence, rare diseases affect 300 million people worldwide. Research on pathogenesis and drug development lags due to limited commercial potential, insufficient epidemiological data, and a dearth of publications. The unique characteristics of rare diseases, including limited annotated data, intricate processes for extracting pertinent entity relationships, and difficulties in standardizing data, represent challenges for text mining. We developed a rare disease data acquisition framework using text mining and knowledge graphs and constructed the most comprehensive rare disease knowledge graph to date, Rare Disease Bridge (RDBridge). RDBridge offers search functions for genes, potential drugs, pathways, literature, and medical imaging data that will support mechanistic research, drug development, diagnosis, and treatment for rare diseases. RDBridge is freely available at http://rdb.lifesynther.com/. Supplementary data are available at Bioinformatics online.

PENGEMBANGAN MEDIA PEMBELAJARAN PENYAKIT LANGKA BERBASIS MULTIMEDIA INTERAKTIF DENGAN METODE LUTHER

The types of rare diseases are currently unknown to many people, especially the general public, due to a lack of information and outreach. Although this disease is very rare, there is a need for early education on its symptoms as a form of anticipation and information and tolerance for sufferers of this disease with the aim of increasing knowledge and awareness about rare diseases. The main problem in this study is the lack of information media for health education about rare diseases, so we need an information media that can present rare disease knowledge that is not only easy to understand but also creative in order to be able to attract people's attention and make learning more fun by creating a interactive multimedia-based learning system. This application is to support understanding of rare diseases, especially for ordinary people who suffer from rare diseases or are around people with rare diseases. The method chosen is the Luther method, which is a multimedia development method based on six stages, namely Concept, Design, Material Collection, Assembly, Testing, and Distribution.

Rare disease education in Europe and beyond: time to act

People living with rare diseases (PLWRD) still face huge unmet needs, in part due to the fact that care systems are not sufficiently aligned with their needs and healthcare workforce (HWF) along their care pathways lacks competencies to efficiently tackle rare disease-specific challenges. Level of rare disease knowledge and awareness among the current and future HWF is insufficient. In recent years, many educational resources on rare diseases have been developed, however, awareness of these resources is still limited and rare disease education is still not sufficiently taken into account by some crucial stakeholders as academia and professional organizations. Therefore, there is a need to fundamentally rethink rare disease education and HWF development across the whole spectrum from students to generalists, specialists and experts, to engage and empower PLWRD, their families and advocates, and to work towards a common coherent and complementary strategy on rare disease education and training in Europe and beyond. Special consideration should be also given to the role of nurse coordinators in care coordination, interprofessional training for integrated multidisciplinary care, patient and family-centered education, opportunities given by digital learning and fostering of social accountability to enforce the focus on socially-vulnerable groups such as PLWRD. The strategy has to be developed and implemented by multiple rare disease education and training providers: universities, medical and nursing schools and their associations, professional organizations, European Reference Networks, patient organizations, other organizations and institutions dedicated to rare diseases and rare cancers, authorities and policy bodies.

Needs of informal caregivers of people with a rare disease: a rapid review of the literature

ObjectivesMany people living with a rare disease (RD) are cared for by a family member. Due to a frequent lack of individual RD knowledge from healthcare professionals, the patient and...

Iranian future healthcare professionals' knowledge and opinions about rare diseases: cross-sectional study

BackgroundRare diseases are a new global health priority, requiring evidence-based estimates of the global prevalence of diseases to inform public policymakers and provide a serious challenge to the healthcare system that must not be ignored. The purpose of this study is to investigate Iranian future healthcare professionals' knowledge and opinions about rare diseases.ResultsA total of 6838 students responded to the questionnaire. Nursing and medical students had the highest participation. Almost 85% of participants rated their knowledge about rare diseases as poor or insufficient. While nearly 70 percent of participants took courses about rare diseases at university. Finally, 72.7% of future healthcare professionals did not feel ready to take care of a patient with a rare disease.ConclusionThe present study has indicated a gap in Iranian medical students’ knowledge of rare diseases. The researchers believe that health science policymakers should make a joint effort to improve knowledge about rare diseases. Including courses with regard to rare diseases would be of benefit to future healthcare professionals.

Think Global, Act Local

Think Global, Act Local

Awareness and Knowledge of Rare Diseases in German Dentists, Dental Specialists and Oral and Maxillofacial Surgeons: A Country-Wide Survey

Background and objectives: Rare diseases affect an estimated four million patients in Germany. Approximately 15% of the approximately 6000 to 8000 rare diseases known globally show manifestations in the dental, oral and maxillofacial regions. The present survey evaluated the knowledge and management of rare diseases and their orofacial alterations by dentists, dental specialists and oral and maxillofacial surgeons and dentists working at university hospitals for dentistry and/or oral and maxillofacial surgery. Materials and Methods: The study was designed as an anonymous cross-sectional study. Two anonymous online surveys were performed in all dentists in Germany using the open-source survey software limesurvey. The study cohorts were divided into dentists, dental specialists and oral and maxillofacial surgeons in practice, and dentists who worked in university dental and oral and maxillofacial surgery centers. The survey was performed between 1 October 2020 and 31 March 2021. Results: A total of 309 dentists and oral and maxillofacial surgeons in private practice and 18 dentists or oral and maxillofacial surgeons working at universities participated. A total of 209 (86.7%) study participants working in private practice indicated that the topic of rare diseases should be considered clinically relevant. University participants indicated that there was a lecture on rare diseases in only 7 (63.6%) cases. Only 2 (13.3%) participants reported active research on the topic in their department. Conclusions: The current knowledge on rare diseases is inadequate in suitable screening and therapy. Most of the participants believed that knowledge of rare diseases was very important for daily dental practice. The self-estimations showed that all of the participants estimated their knowledge as very good or inadequate, with a tendency in the direction of inadequate knowledge.

Poor education and urgent information need for emergency physicians about rare diseases in China

BackgroundRare diseases are serious and chronic diseases that affect no more than 1 person in 2000 (in European Union criteria). Patients suffering from RDs may come to the emergency department for life-threatening symptoms, such as acute aortic dissection, intracranial haemorrhage, and severe respiratory distress. Diagnostic delay of rare disease patients is common and often caused by low rare disease awareness among physicians. The main aim of this study was to investigate Chinese emergency physicians’ basic knowledge, information access and educational needs regarding rare diseases. An online questionnaire was completed by Chinese emergency physicians during January and March 2021.Methods and resultsA total of 539 emergency physicians, including 200 females and 339 males, responded to the questionnaire-based study. More than half of the respondents were from Tertiary A hospitals and had engaged in medical clinical work for more than 10 years. Only 4.27% of respondents correctly estimated the prevalence of rare diseases. A few respondents knew the exact number of RDs in the first official list of rare diseases in 2018. A total of 98.5% of respondents rated their knowledge about rare diseases as minimal or insufficient. Most emergency physicians preferred to obtain information through search engines instead of specialized websites on rare diseases. A lack of practice guidelines or consensus was considered the most important reason for the diagnostic delay of RD. Practice guidelines or consensus and professional websites on rare diseases are urgently needed for emergency physicians.ConclusionThe investigation shows poor knowledge of rare diseases among emergency physicians. Practice guidelines and professional websites on rare diseases were the primary urgent needs for emergency physicians. Specialized RD courses should also be added to medical education.

Epidemiology of rare diseases in Brazil: protocol of the Brazilian Rare Diseases Network (RARAS-BRDN)

The Brazilian Policy of Comprehensive Care for People with Rare Diseases (BPCCPRD) was established by the Ministry of Health to reduce morbidity and mortality and improve the quality of life of people with rare diseases (RD). Several laboratory tests, most using molecular genetic technologies, have been incorporated by the Brazilian Public Health System, and 18 specialised centres have so far been established at university hospitals (UH) in the capitals of the Southern, Southeastern and Northeastern regions. However, whether the available human and technological resources in these services are appropriate and sufficient to achieve the goals of care established by the BPCCPRD is unknown. Despite great advances in diagnosis, especially due to new technologies and the recent structuring of clinical assessment of RD in Brazil, epidemiological data are lacking and when available, restricted to specific disorders. This position paper summarises the performance of a nationally representative survey on epidemiology, clinical status, and diagnostic and therapeutic resources employed for individuals with genetic and non-genetic RD in Brazil. The Brazilian Rare Disease Network (BRDN) is under development, comprising 40 institutions, including 18 UH, 17 Rare Diseases Reference Services and five Newborn Screening Reference Services. A retrospective study will be initially conducted, followed by a prospective study. The data collection instrument will use a standard protocol with sociodemographic data and clinical and diagnostic aspects according to international ontology. This great collaborative network is the first initiative of a large epidemiological data collection of RD in Latin America, and the results will increase the knowledge of RD in Brazil and help health managers to improve national public policy on RD in Brazil.

Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study

BackgroundIn individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process.Study designThis multi-center, prospective controlled study has a two-phase cohort design.MethodsTwo cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2).OutcomesPrimary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach.ConclusionsThis is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease.Trial registration ClinicalTrials.gov; Identifier: NCT03563677; First posted: June 20, 2018, https://clinicaltrials.gov/ct2/show/NCT03563677.

The RareDis corpus: A corpus annotated with rare diseases, their signs and symptoms

Rare diseases affect a small number of people compared to the general population. However, more than 6,000 different rare diseases exist and, in total, they affect more than 300 million people worldwide. Rare diseases share as part of their main problem, the delay in diagnosis and the sparse information available for researchers, clinicians, and patients. Finding a diagnostic can be a very long and frustrating experience for patients and their families. The average diagnostic delay is between 6–8 years. Many of these diseases result in different manifestations among patients, which hampers even more their detection and the correct treatment choice. Therefore, there is an urgent need to increase the scientific and medical knowledge about rare diseases. Natural Language Processing (NLP) can help to extract relevant information about rare diseases to facilitate their diagnosis and treatments, but most NLP techniques require manually annotated corpora. Therefore, our goal is to create a gold standard corpus annotated with rare diseases and their clinical manifestations. It could be used to train and test NLP approaches and the information extracted through NLP could enrich the knowledge of rare diseases, and thereby, help to reduce the diagnostic delay and improve the treatment of rare diseases. The paper describes the selection of 1,041 texts to be included in the corpus, the annotation process and the annotation guidelines. The entities (disease, rare disease, symptom, sign and anaphor) and the relationships (produces, is a, is acron, is synon, increases risk of, anaphora) were annotated. The RareDis corpus contains more than 5,000 rare diseases and almost 6,000 clinical manifestations are annotated. Moreover, the Inter Annotator Agreement evaluation shows a relatively high agreement (F1-measure equal to 83.5% under exact match criteria for the entities and equal to 81.3% for the relations). Based on these results, this corpus is of high quality, supposing a significant step for the field since there is a scarcity of available corpus annotated with rare diseases. This could open the door to further NLP applications, which would facilitate the diagnosis and treatment of these rare diseases and, therefore, would improve dramatically the quality of life of these patients.