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Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare and Effects

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A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Environmental Health".

Deadline for manuscript submissions: closed (30 June 2018) | Viewed by 49472

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Special Issue Editors

Dr. Óscar Zurriaga

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1. Dirección General de Salud Pública, Generalitat Valenciana, Avd. Catalunya, 21, 46020 Valencia, Spain
2. Departamento de Medicina Preventiva y Salud Pública, Universitat de València, Av. Blasco Ibañez, 17, 46010 Valencia, Spain
3. Rare Diseases Research Area, FISABIO-Public Health, Avd. Catalunya, 21, 46020 Valencia, Spain
Interests: rare diseases; diagnosis delay; treatment access; prevention; registries; rare cancers; technological platforms; rare diseases epidemiology; public health surveillance
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Dr. Antoni Montserrat-Moliner

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Directorate of Public Health (SANTE C-1), European Commission, L-2557 Luxembourg, Luxembourg
Interests: rare diseases; orphan drugs; diagnosis delay; reference networks; therapy development; treatment access; prevention; clinical genetics; registries; patients interest; quality of life; rare cancers; technological platforms; economic impact; rare diseases epidemiology

Special Issue Information

Dear Colleagues,

Rare diseases are one of the most challenging issues for healthcare, prevention and research. Patients and their families are expecting for new treatments and more information about their diseases.

Diagnosis is one of the most important issues. There is a critical delay for most cases or there are not appropriate diagnosis techniques to use. Clinical genetics is a clue factor to achieve good diagnosis and good medical care, but healthcare organization is also relevant, inside of a country or at a continental scale. Rare diseases reference networks, like in the European Union, will play an important role in the future.

Important efforts have been made to develop new therapies for rare diseases but there is still a long way to go.

Information, monitoring and surveillance are relevant issues in the rare diseases field. The national and regional strategies and plans for rare diseases are including registries and other information and monitoring tools to increase the knowledge and rare diseases monitoring. Technical, ethical, codification issues and data protection aspects are now being tackled in many countries.

We encourage the rare diseases researchers, clinicians, epidemiologists and patients organizations to join us in this Special Issue about rare diseases and its challenges.

Dr. Óscar Zurriaga
Dr. Antoni Montserrat-Moliner
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Environmental Research and Public Health is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Orphan drug
Diagnosis delay
Reference networks
Rare diseases registries
Rare cancers
Clinical genetics
Patients interests
Quality of life

Related Special Issue

Second Edition of the Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare, and Effects in International Journal of Environmental Research and Public Health (16 articles)

Published Papers (10 papers)

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Research

Jump to: Review

13 pages, 959 KiB

Open AccessArticle

The Epidemiology of Transition into Adulthood of Rare Diseases Patients: Results from a Population-Based Registry

by Monica Mazzucato, Laura Visonà Dalla Pozza, Cinzia Minichiello, Silvia Manea, Sara Barbieri, Ema Toto, Andrea Vianello and Paola Facchin

Int. J. Environ. Res. Public Health 2018, 15(10), 2212; https://doi.org/10.3390/ijerph15102212 - 10 Oct 2018

Cited by 24 | Viewed by 3805

Abstract

Background: Despite the fact that a considerable number of patients diagnosed with childhood-onset rare diseases (RD) survive into adulthood, limited information is available on the epidemiology of this phenomenon, which has a considerable impact both on patients’ care and on the health services. This study describes the epidemiology of transition in a population of RD patients, using data from the Veneto Region Rare Diseases Registry (VRRDR), a web-based registry monitoring since 2002 a consistent number of RD in a defined area (4.9 million inhabitants). Methods: Longitudinal cohorts of patients born in the years 1988 to 1998 and enrolled in the VRRDR in their paediatric age were identified. Data referred to this group of patients, experiencing transition from paediatric to adult age during the years 2006–2016, are presented. Results: 2153 RD patients (44.1% females and 55.9% males) passed from childhood to adulthood in the study period, corresponding to a 3-fold increase from 2006 to 2016. The majority of these patients was affected by congenital anomalies (32.0%), by hematologic diseases (15.9%), eye disorders (12.1%) and neoplasms (7.9%). RD patients who experienced transition from paediatric age to adulthood represent the 9.2% of adult patients enrolled in the Registry at 31 December 2016. Conclusions: We described a subset of RD young adults experiencing transition into adulthood. The data reported can be considered as minimum values for estimating the size of this increasing population presenting specific transition needs. These figures are valuable for clinicians, patients and health planners. Public policy interventions are needed in order to promote dedicated care transition pathways in the broader framework of health policies devoted to RD. Full article

(This article belongs to the Special Issue Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare and Effects)

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12 pages, 8142 KiB

Open AccessArticle

Geographical Accessibility of the Sarcoma Referral Networks in France. Intermediate Results from the IGéAS Research Program

by Yohan Fayet, Jean-Michel Coindre, Cécile Dalban, François Gouin, Gonzague De Pinieux, Fadila Farsi, Françoise Ducimetière, Claire Chemin-Airiau, Myriam Jean-Denis, Sylvie Chabaud, Jean-Yves Blay and Isabelle Ray-Coquard

Int. J. Environ. Res. Public Health 2018, 15(10), 2204; https://doi.org/10.3390/ijerph15102204 - 10 Oct 2018

Cited by 19 | Viewed by 2944

Abstract

Rare cancer patients face lower survival and experience delays in diagnosis and therapeutic mismanagement. Considering the specificities of rare cancers, referral networks have been implemented in France to improve the management and survival of patients. The IGéAS research program aims to assess the networks’ ability to reduce inequalities. Data analysis of the IGéAS cohort (n = 20,590, sarcoma diagnosed between 2011 and 2014) by gathering medical data and geographical index will identify risk factors associated with the belated access to expertise or with no access to expertise. Intermediate results show that referral networks give sarcoma patients access to sarcoma expertise despite the remoteness of some of them. Regional expert centers mostly receive requests from within their area while national referral centers receive requests from the whole country. Delays in the access to expertise may be reduced by making outside practitioners more sensitive to the issues of rare cancers. The perception and involvement of outside practitioners in this device will be assessed using a qualitative survey. All the results are discussed and will contribute to design guidelines to improve early access to expertise and reduce inequalities. Results of the IGéAS research program may contribute to the assessment of referral sarcoma networks and provide some useful lessons to improve cancer care management. Full article

(This article belongs to the Special Issue Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare and Effects)

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13 pages, 2451 KiB

Open AccessArticle

Mining Facebook Data of People with Rare Diseases: A Content-Based and Temporal Analysis

by Laia Subirats, Natalia Reguera, Antonio Miguel Bañón, Beni Gómez-Zúñiga, Julià Minguillón and Manuel Armayones

Int. J. Environ. Res. Public Health 2018, 15(9), 1877; https://doi.org/10.3390/ijerph15091877 - 30 Aug 2018

Cited by 25 | Viewed by 4953

Abstract

This research characterized how Facebook deals with rare diseases. This characterization included a content-based and temporal analysis, and its purpose was to help users interested in rare diseases to maximize the engagement of their posts and to help rare diseases organizations to align their priorities with the interests expressed in social networks. This research used Netvizz to download Facebook data, word clouds in R for text mining, a log-likelihood measure in R to compare texts and TextBlob Python library for sentiment analysis. The Facebook analysis shows that posts with photos and positive comments have the highest engagement. We also observed that words related to diseases, attention, disability and services have a lot of presence in the decalogue of priorities (which serves for all associations to work on the same objectives and provides the lines of action to be followed by political decision makers) and little on Facebook, and words of gratitude are more present on Facebook than in the decalogue. Finally, the temporal analysis shows that there is a high variation between the polarity average and the hour of the day. Full article

(This article belongs to the Special Issue Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare and Effects)

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16 pages, 1467 KiB

Open AccessArticle

SpainUDP: The Spanish Undiagnosed Rare Diseases Program

by Estrella López-Martín, Beatriz Martínez-Delgado, Eva Bermejo-Sánchez, Javier Alonso, The SpainUDP Network and Manuel Posada

Int. J. Environ. Res. Public Health 2018, 15(8), 1746; https://doi.org/10.3390/ijerph15081746 - 14 Aug 2018

Cited by 17 | Viewed by 4603

Abstract

One of the IRDiRC goals for 2017–2027 is to achieve definitive diagnosis for rare undiagnosed diseases within one year, as delay in diagnosis remains one of the pending issues in the rare diseases field. The Spanish Undiagnosed Rare Diseases Program (SpainUDP) was created in response to this challenging scenario to cover patients’ needs and after seeing the success of the Undiagnosed Diseases Program (UDP) in the USA. SpainUDP offers a multidisciplinary approach to those patients who have long sought a diagnosis without any success. During the first phase of the protocol, undiagnosed cases are sent to SpainUDP by individual patients or families, patient organizations or hospitals. After careful analysis of phenotype, data from sequencing experiments (WES) is processed with a standard pipeline and detailed standardized phenotypic information (mapped to the Human Phenotype Ontology, HPO) is connected to genetic data. In addition, the participation of SpainUDP in international initiatives such as the European projects RD-Connect and Solve RD, the Undiagnosed Diseases Network International (UDNI), and the MatchMaker Exchange (MME) platform, allows the establishment of a global data sharing strategy across multiple projects submitting data to these international initiatives. From the official beginning of the program (at the end of 2015) until early 2018, 147 cases were accepted in SpainUDP. During this time, 37 cases (25%) dropped out the program due to several reasons. The remaining 110 cases are distributed as follows: phenotypic and genotypic (WES) characterization was finished in 30 cases, of which 20 (67%) were diagnosed; 21 cases are pending on variants’ validation by Sanger sequencing; in 25 cases, WES is ongoing and 34 cases are being studied for deep phenotypic characterization. In conclusion, SpainUDP aims to achieve a diagnosis following two recommendations of the IRDiRC: the patients’ diagnosis in as short a time as possible and the promotion of data sharing (especially genomic) at the international level. Full article

(This article belongs to the Special Issue Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare and Effects)

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20 pages, 5450 KiB

Open AccessArticle

A Nationwide Registry-Based Study on Mortality Due to Rare Congenital Anomalies

by Verónica Alonso-Ferreira, Germán Sánchez-Díaz, Ana Villaverde-Hueso, Manuel Posada de la Paz and Eva Bermejo-Sánchez

Int. J. Environ. Res. Public Health 2018, 15(8), 1715; https://doi.org/10.3390/ijerph15081715 - 10 Aug 2018

Cited by 6 | Viewed by 3331

Abstract

This study aimed to analyse population-based mortality attributed to rare congenital anomalies (CAs) and assess the associated time trends and geographical differences in Spain. Data on CA-related deaths were sourced from annual mortality databases kept by the National Statistics Institute of Spain (1999–2013). Based on the ICD-10, only CAs corresponding to rare diseases definition were included in this study. Annual age-adjusted mortality rates were calculated and time trends were evaluated by joinpoint regression analysis. Geographical differences were assessed using standardised mortality ratios and cluster detection. A total of 13,660 rare-CA-related deaths (53.4% males) were identified in the study period. Annual age-adjusted mortality rates decreased by an average of −5.2% (−5.5% males, −4.8% females, p < 0.001). Geographical analysis showed a higher risk of rare-CA-related mortality in regions largely located in the south of the country. Despite their limitations, mortality statistics are essential and useful tools for enhancing knowledge of rare disease epidemiology and, by extension, for designing and targeting public health actions. Monitoring rare-CA-related mortality in Spain has shown a 15-year decline and geographical differences in the risk of death, all of which might well be taken into account by the health authorities in order to ensure equality and equity, and to adopt appropriate preventive measures. Full article

(This article belongs to the Special Issue Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare and Effects)

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10 pages, 597 KiB

Open AccessArticle

Oral Symptoms and Oral Health-Related Quality of Life in People with Rare Diseases in Germany: A Cross-Sectional Study

by Sabrina Wiemann, Nicolas Frenzel Baudisch, Rainer A. Jordan, Johannes Kleinheinz and Marcel Hanisch

Int. J. Environ. Res. Public Health 2018, 15(7), 1493; https://doi.org/10.3390/ijerph15071493 - 15 Jul 2018

Cited by 16 | Viewed by 3796

Abstract

Background: The aim of this study was to collect information on oral health-related quality of life (OHRQoL) in people with rare diseases. Methods: A questionnaire comprising free text questions and the German version of the standardized Oral Health Impact Profile-14 (OHIP-14) questionnaire on OHRQoL was developed. All participants who indicated oral symptoms in the questionnaire were included in a cluster analysis. Different cluster analyses were performed (Ward’s, k-Means) to find symptom profile groups in the data. Results: A total of 484 questionnaires with 96 rare diseases were included in the study. The most reported symptoms were anomalies of the tooth formation, dysgnathia, changes in number of the teeth, and malocclusions. The OHIP mean values of the five resulting symptom clusters ranged from 15.1 to 19.9, which is very high compared to the general population in Germany, which has a mean value of 4.09. Discussion: All investigated symptoms show a negative association with OHRQoL, but the strongest were for symptoms of the oral mucosa and periodontal diseases. All the symptoms described in this cluster analysis can lead to considerably higher mean values of the OHIP total score among people with rare disease and thus to worse OHRQoL than reported in the general population. Full article

(This article belongs to the Special Issue Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare and Effects)

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18 pages, 542 KiB

Open AccessArticle

The Occurrence of 275 Rare Diseases and 47 Rare Disease Groups in Italy. Results from the National Registry of Rare Diseases

by Domenica Taruscio, Luciano Vittozzi, Adele Rocchetti, Paola Torreri and Luca Ferrari

Int. J. Environ. Res. Public Health 2018, 15(7), 1470; https://doi.org/10.3390/ijerph15071470 - 12 Jul 2018

Cited by 17 | Viewed by 3790

Abstract

Knowledge of rare diseases (RD) is often scattered among many data collections and registries of patient cohorts. Therefore, assessing the burden of RD in the general population, developing appropriate policies and planning services for the care of RD patients is difficult. This study aimed at providing a systematic picture of RD occurrence in a population as big as 60 million. Data of diagnoses were certified and collected by a network of 247 specialized centres covering the whole Italian territory. Data received (about 200,000 records) were validated according to formal criteria and, where necessary, corrected by the data sources. Data of age at onset and sex distribution are given for about 400 diseases. Incidence and/or birth prevalence are given for 275 diseases and 47 disease groups, which, altogether, comprise a substantial part of the known rare diseases. Data quality, internal consistency, and external validity of the database have also been assessed and ways to limit the impact of some discrepancies were devised. The information provided by RNMR, cutting across such a wide range of RD, represents a unique coherent basis allowing the prioritization of relevant public health measures and research activities. Full article

(This article belongs to the Special Issue Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare and Effects)

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9 pages, 535 KiB

Open AccessArticle

General Practice Care for Patients with Rare Diseases in Belgium. A Cross-Sectional Survey

by Nicole Boffin, Elfriede Swinnen, Johan Wens, Montse Urbina, Johan Van der Heyden and Viviane Van Casteren

Int. J. Environ. Res. Public Health 2018, 15(6), 1180; https://doi.org/10.3390/ijerph15061180 - 05 Jun 2018

Cited by 12 | Viewed by 3121

Abstract

There are almost no studies about rare diseases in general practice. This study examined care characteristics of active rare disease patients in the Belgian Network of Sentinel General Practices (SGP) and the importance of rare diseases in general practice by its caseload, general practitioner (GP)–patient encounter frequency and nationwide prevalence. The SGP reported data about: (i) the number of active rare disease patients in 2015; and (ii) characteristics of one to three most recently seen patients. Rare diseases were matched against Orphanet (www.orpha.net). GP encounter frequency and patients’ age were compared to the total general practice population. Details from 121 active patients (median age: 44, interquartile range (IQR) 24–60) showed that for 36.9% the GP had been the first caregiver for the rare disease and for 35.8% the GP established a diagnostic referral. GPs rated their knowledge about their patients’ disease as moderate and used Orphanet for 14.9% of patients. Any active rare disease patients (median: 1, IQR 0–2) were reported by 66 of 111 SGP. Compared to the total general practice population, the mean GP encounter frequency was higher (7.3; 95% confidence intervals (CI) 6.1–8.5 versus 5.4; 95% CI 5.4–5.4). The prevalence of rare diseases in the Belgian general practice population was estimated at 12.0 (95% CI 10.3–13.9) per 10,000. This study acknowledges the important role of GPs in rare disease care. Knowledge and use of Orphanet by GPs could be improved. Full article

(This article belongs to the Special Issue Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare and Effects)

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Review

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16 pages, 335 KiB

Open AccessReview

Meeting Patients’ Right to the Correct Diagnosis: Ongoing International Initiatives on Undiagnosed Rare Diseases and Ethical and Social Issues

by Sabina Gainotti, Deborah Mascalzoni, Virginie Bros-Facer, Carlo Petrini, Giovanna Floridia, Marco Roos, Marco Salvatore and Domenica Taruscio

Int. J. Environ. Res. Public Health 2018, 15(10), 2072; https://doi.org/10.3390/ijerph15102072 - 21 Sep 2018

Cited by 36 | Viewed by 5464

Abstract

The time required to reach a correct diagnosis is a key concern for rare disease (RD) patients. Diagnostic delay can be intolerably long, often described as an “odyssey” and, for some, a diagnosis may remain frustratingly elusive. The International Rare Disease Research Consortium proposed, as ultimate goal for 2017–2027, to enable all people with a suspected RD to be diagnosed within one year of presentation, if the disorder is known. Subsequently, unsolved cases would enter a globally coordinated diagnostic and research pipeline. In-depth analysis of the genotype through next generation sequencing, together with a standardized in-depth phenotype description and sophisticated high-throughput approaches, have been applied as diagnostic tools to increase the chance of a timely and accurate diagnosis. The success of this approach is evident in the Orphanet database. From 2010 to March 2017 over 600 new RDs and roughly 3600 linked genes have been described and identified. However, combination of -omics and phenotype data, as well as international sharing of this information, has raised ethical concerns. Values to be assessed include not only patient autonomy but also family implications, beneficence, non-maleficence, justice, solidarity and reciprocity, which must be respected and promoted and, at the same time, balanced among each other. In this work we suggest that, to maximize patients’ involvement in the search for a diagnosis and identification of new causative genes, undiagnosed patients should have the possibility to: (1) actively participate in the description of their phenotype; (2) choose the level of visibility of their profile in matchmaking databases; (3) express their preferences regarding return of new findings, in particular which level of Variant of Unknown Significance (VUS) significance should be considered relevant to them. The quality of the relationship between individual patients and physicians, and between the patient community and the scientific community, is critically important for optimizing the use of available data and enabling international collaboration in order to provide a diagnosis, and the attached support, to unsolved cases. The contribution of patients to collecting and coding data comprehensively is critical for efficient use of data downstream of data collection. Full article

(This article belongs to the Special Issue Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare and Effects)

22 pages, 777 KiB

Open AccessReview

Recommendations for Improving the Quality of Rare Disease Registries

by Yllka Kodra, Jérôme Weinbach, Manuel Posada-de-la-Paz, Alessio Coi, S. Lydie Lemonnier, David Van Enckevort, Marco Roos, Annika Jacobsen, Ronald Cornet, S. Faisal Ahmed, Virginie Bros-Facer, Veronica Popa, Marieke Van Meel, Daniel Renault, Rainald Von Gizycki, Michele Santoro, Paul Landais, Paola Torreri, Claudio Carta, Deborah Mascalzoni, Sabina Gainotti, Estrella Lopez, Anna Ambrosini, Heimo Müller, Robert Reis, Fabrizio Bianchi, Yaffa R. Rubinstein, Hanns Lochmüller and Domenica Taruscio Show full author list Hide full author list

Int. J. Environ. Res. Public Health 2018, 15(8), 1644; https://doi.org/10.3390/ijerph15081644 - 03 Aug 2018

Cited by 112 | Viewed by 12768

Abstract

Rare diseases (RD) patient registries are powerful instruments that help develop clinical research, facilitate the planning of appropriate clinical trials, improve patient care, and support healthcare management. They constitute a key information system that supports the activities of European Reference Networks (ERNs) on rare diseases. A rapid proliferation of RD registries has occurred during the last years and there is a need to develop guidance for the minimum requirements, recommendations and standards necessary to maintain a high-quality registry. In response to these heterogeneities, in the framework of RD-Connect, a European platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research, we report on a list of recommendations, developed by a group of experts, including members of patient organizations, to be used as a framework for improving the quality of RD registries. This list includes aspects of governance, Findable, Accessible, Interoperable and Reusable (FAIR) data and information, infrastructure, documentation, training, and quality audit. The list is intended to be used by established as well as new RD registries. Further work includes the development of a toolkit to enable continuous assessment and improvement of their organizational and data quality. Full article

(This article belongs to the Special Issue Current Situation and Distribution of Rare Diseases: Challenges, Prevention, Healthcare and Effects)

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