Ter Arkh. 2022 Oct 12;94(8):992-998. doi: 10.26442/00403660.2022.08.201833.

ABSTRACT

The first documented case of mitochondrial neurogastrointestinal encephalomyopathy was described in 1962 by R. Luft. The variety and am-biguity of the clinical manifestations of the disease complicate its early diagnosis and treatment. The first clinical manifestations of the disease are associated with the pathology of the gastrointestinal tract. Low alertness and insufficient awareness of doctors delays the timely diagnosis of mitochondrial neurogastrointestinal encephalomyopathy. The aim of the work is to increase the alertness and awareness of narrow specialties about the possibility of differential diagnosis of an extremely rare detected disease on the base of our clinical observation.

PMID:36286980 | DOI:10.26442/00403660.2022.08.201833

Rev Neurol. 2022 Nov 1;75(9):261-267. doi: 10.33588/rn.7509.2022298.

ABSTRACT

INTRODUCTION: Spinal muscular atrophy (SMA) is a rare disease whose diagnosis and treatment are complex. In Spain, there are two orphan medicines that are currently financed by the state, nusinersen and onasemnogene abeparvovec and, a third in process, risdiplam. The objective was to detect possible causes of inequity in the diagnosis and treatment of SMA in Spain.

MATERIALS AND METHOD: Descriptive study realized in two phases: a first phase of bibliographic revision and a second phase of semi-structured interviews with clinical experts in SMA in Andalusia, Castilla-La Mancha, Catalonia and Murcia.

RESULTS: The number of centers, services or units of reference, the availability of regional autonomous plans for rare diseases and pilot programs of neonatal screenings can regulate access to treatments. The number of new patients diagnosed per year is estimated between one and six in the four autonomous communities (ACs) of Spain studied. Differences were not found in logistical resources. Two of the four ACs studied have regional autonomous plans for rare diseases, however, their utility has only had relevance in one of two of the ACs.

CONCLUSIONS: Important differences in access to nusinersen were not identified in the studied ACs The diagnosis of SMA requires clinical specialized experts and specialized centers for early intervention of disease-modifying therapies.

PMID:36285446 | DOI:10.33588/rn.7509.2022298

Vnitr Lek. 2022 Fall;68(E-5):4-19. doi: 10.36290/vnl.2022.070.

ABSTRACT

Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder. Autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum, prostate and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD and in 2019 four Clinical phenotypes of IgG4-related disease were described. Diagnosis is based on morphological examination with typical findings of lymphoplasmocellular inflammation, storiform fibrosis and obliterative phlebitis in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. New diagnostic criteria for IgG4-RD have been published recently in 2019 and 2021. This review summarizes current knowledge on pathophysiology, clinical manifestations, diagnosis and differential diagnosis of IgG4-RD from the point of view 2022 and in next article brings overview of the IgG4-RD therapy.

PMID:36283812 | DOI:10.36290/vnl.2022.070

Medicine (Baltimore). 2022 Oct 21;101(42):e31060. doi: 10.1097/MD.0000000000031060.

ABSTRACT

BACKGROUND: Fabry disease (FD) is a rare, inherited disease lysosomal storage disorder caused by the lack of an alpha-galactosidase enzyme. This genetic disease can affect both men and women. The understanding of FD is very important as this condition can be effectively treated. For women who may exhibit normal residual enzyme activity, the diagnosis is more challenging.

CASE PRESENTATION: Herein, we reported on a case of IgA nephropathy and renal disease that mimicked FD in a female patient. The presence of zebra bodies in the cytoplasm of glomerular podocytes is widely accepted as a hallmark pathological manifestation of FD. In the present case, renal biopsy analysis revealed the presence of zebra bodies; however, genetic testing indicated that the patient did not have FD. The mechanisms and causes of zebra body formation remained unclear in the present case. However, the patient responded well to treatment with an angiotensin receptor blocker.

CONCLUSIONS: The reported findings can be useful for the differential diagnosis of FD and renal diseases in the future. Our results also highlight the clinical significance of zebra bodies in renal disease.

PMID:36281086 | DOI:10.1097/MD.0000000000031060

J Clin Invest. 2022 Oct 25:e163235. doi: 10.1172/JCI163235. Online ahead of print.

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients following acute infection with SARS-CoV-2 by hitherto unknown mechanisms. Whereas acute-COVID-19 severity and outcome were previously correlated with Notch4 expression on regulatory T (Treg) cells, here we show that the Treg cells in MIS-C are destabilized through a Notch1-dependent mechanism. Genetic analysis revealed that MIS-C patients were enriched in rare deleterious variants impacting inflammation and autoimmunity pathways, including dominant-negative mutations in the Notch1 regulators NUMB and NUMBL leading to Notch1 upregulation. Notch1 signaling in Treg cells induced CD22, leading to their destabilization in a mTORC1-dependent manner and to the promotion of systemic inflammation. These results establish a Notch1-CD22 signaling axis that disrupts Treg cell function in MIS-C and point to distinct immune checkpoints controlled by individual Treg cell Notch receptors that shape the inflammatory outcome in SARS-CoV-2 infection.

PMID:36282598 | DOI:10.1172/JCI163235

Soc Sci Med. 2022 Dec;314:115465. doi: 10.1016/j.socscimed.2022.115465. Epub 2022 Oct 19.

ABSTRACT

This study explores parental expectations and value-making processes in respect to pediatric clinical genomic sequencing for socially disadvantaged families. Drawing on interviews and ethnographic observations with parents of children with undiagnosed physical and/or intellectual differences seeking to find whether these differences have a genetic etiology, we explore expectations and parental assessments of the value of genomic sequencing within the context of an ongoing research study. We demonstrate how the value of sequencing to parents goes well beyond finding diagnostic results or receiving prescriptive guidance as to the best care and treatment of their child; instead, value is co-created by parents, clinicians, and genetic counsellors throughout the enrollment and return of results process. Parents in our study found that clinicians and genetic counsellors repeatedly reenforce that parents need to lower their expectations and be prepared to wait for genetic science to provide more definitive answers. At the same time, parents experience that clinical teams validate parents for having made a good choice in their undertaking of genomic sequencing and, no matter the result, that they are not to blame for their child's symptoms. The experience of many parents (although not all) is that genomic science reduces or removes their sense of guilt for their child's condition, providing a platform that affirms them as "good parents." Moreover, rather than being voiceless and isolated, socially disadvantaged parents who enter into diagnostic sequencing find themselves in a familial-biosocial framework wherein they are co-partners in a socially and biologically authoritative vision of the future.

PMID:36279794 | DOI:10.1016/j.socscimed.2022.115465

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2022 Nov;65(11):1143-1150. doi: 10.1007/s00103-022-03599-8. Epub 2022 Oct 24.

ABSTRACT

An electronic patient record offers opportunities for digital networks between medical care providers and for the digital communication between health service providers and their patients. Patients with rare diseases benefit from a diagnosis and treatment information at an early stage and receive precise treatment on the basis of multiprofessional case management. Regarding the patient care and medical research in rare diseases, electronic patient records can help to collect all data in a structured manner and to digitally map the workflows in registration, admission, diagnosis, and treatment. This can reduce costs in our healthcare system, as diagnosis and treatment can be targeted better at the patients and unnecessary medical examinations can be reduced.In two pilot projects, first experiences with electronic patient records for patients with rare diseases were gathered. In cooperation with several medical care providers, the projects BASE-Netz and TRANSLATE-NAMSE analyzed the requirements of an electronic patient record, demonstrated the technical and legal feasibility, and evaluated the practicability for medical care providers and patients. The participating centers for rare diseases see benefits in the structured registration of the patients and the simplification of cross-institutional patient management, as patients can fulfil more tasks on their own and the health professionals can easily share data. The development of the Telematikinfrastructure of the Gematik offers opportunities to ease the digital connection between doctors' offices and the center for rare diseases. In particular, constant clarification and transparency are essential in order to provide information on data protection issues. Training and support should also be provided to promote patients' digital skills.

PMID:36278976 | PMC:PMC9636298 | DOI:10.1007/s00103-022-03599-8

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2022 Nov;65(11):1159-1163. doi: 10.1007/s00103-022-03602-2. Epub 2022 Oct 24.

ABSTRACT

Rare diseases can often be diagnosed by carefully assessing the phenotype of the patient, as characteristic deviations (dysmorphisms) occur in many genetic diseases. These affect, for example, the features of the face - the "facial gestalt."This paper highlights an area of artificial intelligence (AI) in which there has been great progress in recent years: the recognition of characteristic patterns in medical image data using deep, convolutional neural networks (next-generation phenotyping - NGP). The technical basis of the method is briefly described and the high relevance of FAIR data for the scientific community to develop AI is discussed. Furthermore, it is explained why decisions made by AI should always remain comprehensible and how it can overcome the challenges with regard to data protection and transparency.In the future, software applications with AI will support medical professionals in the diagnosis of rare diseases. AI will be trustworthy if patients retain their data sovereignty and can understand how the diagnosis was made.

PMID:36278975 | PMC:PMC9636278 | DOI:10.1007/s00103-022-03602-2

Orphanet J Rare Dis. 2022 Oct 21;17(1):380. doi: 10.1186/s13023-022-02504-5.

ABSTRACT

BACKGROUND: People with rare disorders face significant global health inequalities; the challenge is how to raise awareness and develop a nucleus of experts in a country who are then able to provide guidance to others in that country. The International Prader-Willi Syndrome Organisation (IPWSO) established Project ECHO® with the aim of facilitating the sharing of knowledge and the building of international partnerships to reduce global health inequalities for a particular rare genetically-determined neurodevelopmental disorder, Prader-Willi Syndrome (PWS). Four different ECHO programmes were established for the following groups: (a) Individuals (usually parents) who had taken on a leadership role in their country; (b) health professionals interested in PWS; (c) professional care providers supporting children and adults with PWS; and (d) a Latin American ECHO in Spanish. The programme started in 2020 and an evaluation was undertaken after one year to determine: the extent to which IPWSO had been able to recruit and retain individuals globally; the nature and extent of any benefits gained from the sessions; and examples of how individual involvement in the programme had led to local benefits. The methods included analysing routinely kept process indicators and survey data from the attendees of one component of the programme (the Leadership ECHO), together with a qualitative analysis of survey data and recorded interviews of attendees from countries of differing socio-economic status.

RESULTS: We describe the IPWSO ECHO programme and report on the outcomes from the evaluation of one aspect of the programme, the Leadership ECHO. Attendance of the Leadership ECHO sessions was satisfactory, with a mean of 24.7 participants, with participants attending a mean of 5.67 sessions, i.e., 30% of sessions. There was also good global reach, with individuals attending from 34 countries, although there were notable geographic regions with very limited representation. Feedback and interviews demonstrated the positive impact of the programme with some early evidence of positive developments at national level.

CONCLUSIONS: Families and professionals from countries with a range of expertise and services offered to people with PWS remained engaged throughout the ECHO programme, established networks of support and fostered the development of good practice.

PMID:36271403 | PMC:PMC9587665 | DOI:10.1186/s13023-022-02504-5

Front Oncol. 2022 Oct 4;12:970199. doi: 10.3389/fonc.2022.970199. eCollection 2022.

ABSTRACT

Collecting duct renal cell carcinoma (cdRCC), which until recently was thought to arise from the collecting ducts of Bellini in the renal medulla, is a rare and aggressive type of non-clear renal cell carcinoma (ncRCC), accounting for 1% of all renal tumors and with nearly 50% of patients being diagnosed with Stage IV disease. The median overall survival in this setting is less than 12 months. Several regimens of chemotherapies had been used based on morphologic and cytogenetic similarities with urothelial cell carcinoma described previously, although the prognosis still remains poor. The use of targeted therapies also did not result in favorable outcomes. Recent works using NGS have highlighted genomic alterations in SETD2, CDKN2A, SMARCB1, and NF2. Moreover, transcriptomic studies have confirmed the differences between urothelial carcinoma and cdRCC, the possible true origin of this disease in the distal convoluted tubule (DCT), differentiating from other RCC (e.g., clear cell and papillary) that derive from the proximal convoluted tubule (PCT), and enrichment in immune cells that may harbor insights in novel treatment strategies with immunotherapy and target agents. In this review, we update the current aspects of the clinical, molecular characterization, and new targeted therapeutic options for Collecting duct carcinoma and highlight the future perspectives of treatment in this setting.

PMID:36267983 | PMC:PMC9577600 | DOI:10.3389/fonc.2022.970199

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2022 Nov;65(11):1170-1177. doi: 10.1007/s00103-022-03605-z. Epub 2022 Oct 20.

ABSTRACT

Knowledge generation in the field of drug development for people with rare diseases (RDs) faces particular difficulties. This paper will show what improvements are expected from increasing digitalisation from the perspective of three healthcare institutions: the Federal Institute for Drugs and Medical Devices, the Institute for Quality and Efficiency in Health Care and the Federal Joint Committee.First, the potential of digitalisation to increase the efficiency of clinical development and regulatory decision-making through earlier collaboration of all stakeholders is proposed. Subsequently, it is argued that digitalisation should be used to reduce barriers to the implementation of care-associated randomised controlled trials, including those based on registries. High-quality registry studies should not only be started after approval but during the approval process, so that the evidence necessary for therapy decisions is available promptly after approval. Finally, it is stated that improving the evidence base through qualitative improvement of the data sources and their linkages directly benefits patients. Usable evidence that can be generated over a longer period of time - also beyond approval - and contribute to decisions within healthcare system ensures effective drug provision.The institutions agree that high-quality indication registries should be developed as product-independent, standing infrastructures so that high-quality data can be accessed early in the development of medicines for RD.

PMID:36264322 | PMC:PMC9636280 | DOI:10.1007/s00103-022-03605-z

Neurotherapeutics. 2022 Oct 20. doi: 10.1007/s13311-022-01314-8. Online ahead of print.

NO ABSTRACT

PMID:36266502 | DOI:10.1007/s13311-022-01314-8

Cardiovasc Intervent Radiol. 2022 Oct 19. doi: 10.1007/s00270-022-03296-8. Online ahead of print.

ABSTRACT

PURPOSE: Arteriovenous malformations (AVMs) as rare diseases are diagnostically and therapeutically challenging. Due to the limited evidence regarding treatment outcome, prospective data are needed on how different treatment regimens affect outcome. The aims of this prospective trial are to determine effectiveness, safety, and clinical outcome of multimodal treatment in patients with extracranial AVMs.

MATERIALS AND METHODS: After clinical and magnetic resonance imaging (MRI)-based diagnosis and informed consent, 146 patients (> 4 years and < 70 years) undergoing multimodal therapy in tertiary care vascular anomalies centers will be included in this prospective observational trial. Treatment options include conservative management, medical therapy, minimally invasive image-guided procedures (embolization, sclerotherapy) and surgery as well as combinations of the latter. The primary outcome is the patient-reported QoL 6 months after completion of treatment using the short form-36 health survey version 2 (SF-36v2) and the corresponding short form-10 health survey (SF-10) for children. In addition, clinical presentation (physician-reported signs), MRI imaging (radiological assessment of devascularization), recurrence rate, and therapeutic safety will be analyzed. Further follow-up will be performed after 12, 24, and 36 months. Moreover, liquid biopsies are being obtained from peripheral blood at multiple time points to investigate potential biomarkers for therapy response and disease progression.

DISCUSSION: The APOLLON trial is a prospective, multicenter, observational open-label trial with unequal study groups to generate prospective evidence for multimodal treatment of AVMs. A multicenter design with the potential to assess larger populations will provide an increased understanding of multimodal therapy outcome in this orphan disease.

TRIAL REGISTRATION: German Clinical Trials Register (identification number: DRKS00021019) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021019 .

PMID:36261507 | DOI:10.1007/s00270-022-03296-8

J Mol Recognit. 2022 Oct 19:e2997. doi: 10.1002/jmr.2997. Online ahead of print.

ABSTRACT

Schizophrenia is mental illness affecting the normal lifestyle of adults and early adolescents incurring major symptoms as jumbled speech, involvement in everyday activities eventually got reduced, patients always struggle with attention and memory, reason being both the genetic and environmental factors are responsible for altered brain chemistry and structure, resulting in schizophrenia and associated orphan diseases. The network biology describes the interactions among genes/proteins encoding molecular mechanisms of biological processes, development, and diseases. Besides, all the molecular networks, protein-protein Interaction Networks have been significant in distinguishing the pathogenesis of diseases and thereby drug discovery. The present meta-analysis prioritizes novel diseases indications viz. rare and orphan diseases associated with target Glutamate Ionotropic Receptor NMDA Type Subunit 1, GRIN1 using text mining knowledge-based tools. Further, ZINC database was virtually screened, and binding conformation of selected compounds was performed and resulted in the identification of Narciclasine (ZINC04097652) and Alvespimycin (ZINC73138787) as potential inhibitors. Further, docked complexes were subjected to MD simulation studies which suggests the identified leads could be a better potential drug to recuperate schizophrenia. This article is protected by copyright. All rights reserved.

PMID:36259267 | DOI:10.1002/jmr.2997

J Biomed Inform. 2022 Nov;135:104227. doi: 10.1016/j.jbi.2022.104227. Epub 2022 Oct 17.

ABSTRACT

Although individually rare, collectively more than 7,000 rare diseases affect about 10% of patients. Each of the rare diseases impacts the quality of life for patients and their families, and incurs significant societal costs. The low prevalence of each rare disease causes formidable challenges in accurately diagnosing and caring for these patients and engaging participants in research to advance treatments. Deep learning has advanced many scientific fields and has been applied to many healthcare tasks. This study reviewed the current uses of deep learning to advance rare disease research. Among the 332 reviewed articles, we found that deep learning has been actively used for rare neoplastic diseases (250/332), followed by rare genetic diseases (170/332) and rare neurological diseases (127/332). Convolutional neural networks (307/332) were the most frequently used deep learning architecture, presumably because image data were the most commonly available data type in rare disease research. Diagnosis is the main focus of rare disease research using deep learning (263/332). We summarized the challenges and future research directions for leveraging deep learning to advance rare disease research.

PMID:36257483 | DOI:10.1016/j.jbi.2022.104227

Orphanet J Rare Dis. 2022 Oct 17;17(1):375. doi: 10.1186/s13023-022-02525-0.

ABSTRACT

BACKGROUND: Caring for a child with a chronic disease may be demanding and stressful. When a child has a rare condition, the impact of care on parents is amplified due to the rarity of the diagnosis. In order to address the lack of generalized and synthesized knowledge regarding parents' experiences of having a child with a rare genetic disorder, and give a holistic picture of these experiences, a systematic review of the available qualitative research was conducted.

METHODS: We performed a systematic review, including qualitative studies on parents of children with rare genetic disorders, published between 2000 and 2020.

RESULTS: The review included 33 qualitative studies. Findings were synthesized and categorized according to three main themes: Parents' experiences with health care, Responsibilities and challenges, and Factors promoting positive experiences in parents. The findings demonstrate that parents of children with rare genetic disorders share many common challenges, despite evident differences across conditions.

CONCLUSION: Coordinated care, and a more holistic approach in the follow up of children with rare genetic disorders is needed. International collaboration on research, diagnostics, producing scientific correct and understandable information available for health care professionals and lay people should be prioritized.

PMID:36253830 | DOI:10.1186/s13023-022-02525-0

Am J Manag Care. 2022 Oct 1;28(10):e351-e354. doi: 10.37765/ajmc.2022.89252.

ABSTRACT

Pharmacoeconomic analyses are an important and useful guide for understanding a pharmacotherapeutic intervention's financial impact for relevant stakeholders. One type of pharmacoeconomic analysis that assesses a pharmacotherapeutic intervention's short-term financial implications is a budget impact analysis. Although methodology guidelines for budget impact analyses in the United States currently exist, not much guidance is available for analyses that are being conducted of rare or ultrarare disease states. In this article, we propose conducting a scenario analysis for pharmacotherapeutic interventions to treat rare diseases by varying health plan sizes to indicate what the potential plan impact would be if 1 member in said health plan received treatment. We then walk through an illustrative example and discuss the rationale for it.

PMID:36252174 | DOI:10.37765/ajmc.2022.89252

Orphanet J Rare Dis. 2022 Oct 17;17(1):362. doi: 10.1186/s13023-022-02517-0.

ABSTRACT

Lysosomal storage disorders (LSD) are rare diseases, caused by inherited deficiencies of lysosomal enzymes/transporters, that affect 1 in 7000 to 1 in 8000 newborns. Individuals with LSDs face long diagnostic journeys during which debilitating and life-threatening events can occur. Clinical trials and classical descriptions of LSDs typically focus on common manifestations, which are not representative of the vast phenotypic heterogeneity encountered in real-world experience. Additionally, recognizing that there was a limited understanding of the natural history, disease progression, and real-world clinical outcomes of rare LSDs, a collaborative partnership was pioneered 30 years ago to address these gaps. The Rare Disease Registries (RDR) (for Gaucher, Fabry, Mucopolysaccharidosis type I, and Pompe), represent the largest observational database for these LSDs. Over the past thirty years, data from the RDRs have helped to inform scientific understanding and the development of comprehensive monitoring and treatment guidelines by creating a framework for data collection and establishing a standard of care, with an overarching goal to improve the quality of life of affected patients. Here, we highlight the history, process, and impact of the RDRs, and discuss the lessons learned and future directions.

PMID:36244992 | PMC:PMC9573793 | DOI:10.1186/s13023-022-02517-0

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2022 Nov;65(11):1119-1125. doi: 10.1007/s00103-022-03597-w. Epub 2022 Oct 14.

ABSTRACT

People with rare diseases face specific challenges within the healthcare system. Due to the rarity of the individual diseases, both medical care and research are made difficult for structural, medical, and economic reasons. In 2010, the National Action League for People with Rare Diseases (NAMSE) was founded by the German Federal Ministry of Health, the German Federal Ministry of Education and Research, the Alliance for Chronic Rare Diseases, as well as 25 other partners. Since then, NAMSE has been the central coordination and communications platform for people with rare diseases in Germany and aims to improve the health and quality of life of those affected.As part of the consensus process, NAMSE has formulated requirements regarding digitization in the German healthcare system. These requirements aim towards connecting healthcare institutions, generating knowledge for research purposes, and improving the flow of information. The main objective is a collective and secure health data space with interoperable clinic information systems and uniform semantic standards. The precise coding of rare diseases is of particular importance.In the coming years, important processes that have already been initiated must be designed and supported in the interest of people with rare diseases. These include the German genome initiative genomDE, the implementation of the electronic patient record, and activities towards a European Health Data Space. In order for the diverse initiatives and projects to mesh, clear objectives are required as part of an overall digital concept to which NAMSE makes important contributions.

PMID:36239769 | PMC:PMC9636091 | DOI:10.1007/s00103-022-03597-w

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2022 Nov;65(11):1133-1142. doi: 10.1007/s00103-022-03598-9. Epub 2022 Oct 14.

ABSTRACT

The ICD-10-GM coding system used in the German healthcare system only captures a minority of rare disease diagnoses. Therefore, information on the incidence and prevalence of rare diseases as well as necessary (financial) resources for the expert care required for evidence-based decisions by health insurers, care providers, and politicians are lacking. Furthermore, the missing information complicates and sometimes even precludes the generation of scientific knowledge on rare diseases. Therefore, starting in 2023, all in-patient cases in Germany with a rare disease diagnosis must be coded by an ORPHAcode using the Alpha-ID-SE file.The file Alpha-ID-SE links the ICD-10-GM codes to the internationally established ORPHAcodes for rare diseases. Commercially available software tools progressively support the coding of rare diseases. In several centers for rare diseases linked to university hospitals, IT tools and procedures were established to realize a complete coding of rare diseases. These include financial incentives for the institutions providing rare disease codes, systematic queries asking for rare disease codes during the coding process, and a semi-automated coding process for all patients with a rare disease previously seen at the institution. A combination of the different approaches probably results in the most complete coding.To get the complete picture of rare disease epidemiology and care requirements, a specific and unique coding of out-patient cases is also desirable. Furthermore, a structured reporting of phenotype is required, especially for complex rare diseases and for yet undiagnosed cases.

PMID:36239768 | PMC:PMC9636302 | DOI:10.1007/s00103-022-03598-9