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Editors

HelenaKääriäinen
SatuWedenoja

Rare Diseases

Essentials

  • According to the European definition, a disease is classified as rare if present in no more than 5 people in 10 000. Many rare diseases are even considerably rarer than this.
  • As more than 7 000 rare diseases have been described, together they form a large group of diseases.
  • The estimated global prevalence of rare diseases is 3.5-5.9 %, corresponding to 263-446 million persons, excluding some conditions http://www.nature.com/articles/s41431-019-0508-0. The share is probably a lot bigger among those needing a lot of health care services.
  • Data on the prevalence of rare diseases are unreliable because only a few of these diseases have ICD-10 codes.

General remarks

Suspicion of a rare disease

  • In children, rare diseases often involve abnormal growth or development. Particularly if a child shows an abnormal build or appearance in addition to developmental problems, the child probably has a rare disease. All visual and hearing handicaps and many unusual dermatological symptoms in children belong to the group of rare diseases.
  • In adults, the presence of a rare disease may be suggested by a strange combination of symptoms or symptoms that are common as such but occur at the wrong age.
  • A rare infection should be suspected if the patient has returned from an exotic trip.
  • If cancer is suspected, the patient should be referred normally and a rare cancer may be detected as diagnostic investigations proceed.

Diagnosis

  • Most of the diseases are genetic, and today quite extensive genomic investigations are performed for diagnosis, often revealing the exact cause of the disease and, at the same time, providing information about any risk of inheritance.
  • In the case of some diseases, special investigations, such as metabolic tests, possibly done at a laboratory abroad, are needed to confirm the diagnosis.
  • The exact diagnosis of a disease can often not be made by any available tests, and unless a specialized clinic can diagnose it, colleagues abroad are usually consulted. European Reference Networks (ERNs) http://health.ec.europa.eu/european-reference-networks/overview_en are particularly helpful in such cases. Each of the networks of expertise in 24 fields of medicine has members from many countries; see Table T1.
  • Yet, it is far from always possible to define or confirm the diagnosis, and patients may therefore remain unsure of factors such as the prognosis or risk of recurrence of the disease. A new attempt to redefine the diagnosis after a few years, for instance, is recommended, particularly if the patient's or family's situation changes.
  • Specialized centres usually offer patients and families the possibility of genetic counselling.

European Reference Networks (ERNs)

ERNSubject area
ERN BONDRare bone diseases
ERN CRANIOCraniofacial anomalies and rare ear, nose and throat (ENT) disorders
Endo-ERNRare endocrine conditions
ERN EpiCARERare epilepsies
ERKNetRare kidney diseases
ERN-RNDRare neurological diseases
ERNICARare inherited and congenital (digestive and gastrointestinal) anomalies
ERN LUNGRare respiratory diseases
ERN SkinRare skin disorders
ERN EURACANRare adult cancers (solid tumours)
ERN EuroBloodNetRare haematological diseases
ERN eUROGENRare urogenital diseases
ERN EURO-NMDRare neuromuscular diseases
ERN EYERare eye diseases
ERN GENTURISRare genetic tumour risk syndromes
ERN GUARD-HEARTRare diseases of the heart
ERN ITHACARare malformation syndromes, intellectual and other neurodevelopmental disorders
MetabERNHereditary metabolic disorders
ERN PaedCanPaediatric oncology
ERN RARE-LIVERRare liver diseases
ERN ReCONNETRare connective tissue and musculoskeletal diseases diseases
ERN RITARare immunodeficiency, autoinflammatory and autoimmune disorders
ERN TRANSPLANT-CHILDPaediatric transplantation
VASCERNRare vascular diseases

Treatment and follow-up

  • Ideally, the specialist best familiar with the disease in a centre of expertise in the patient's own country should take care of the patient's treatment and follow-up throughout the patient's lifetime. However, this is not always possible and, in practice, patients are usually treated and followed up by various professionals on different levels of health care according to instructions given by a specialized centre.
  • There is rarely specific medication available for rare diseases but any such medication should be started at a specialized centre, as necessary.
  • Patients are often polysymptomatic and need many kinds of support and services and various social benefits.
  • Patients with rare diseases should also be referred for peer support and engagement in various organizations for rare diseases.
  • For polysymptomatic patients, in particular, it is important to be supported by a person coordinating the complicated treatment and social benefit issues, such as the doctor or nurse treating the patient.

Information sources

  • For many or most rare diseases, there may be very little information available in the patient's own language, particularly in the case of smaller languages.
  • Table T2 lists English websites providing reliable information. Patients and their families often have many questions; these sources will provide answers to some of them.
  • Find out about further information sources in the local language.
  • Some rare diseases are called ultra-rare. Information on such diseases is often based on single publications the doctor can find in PubMed and try to interpret for the patient.
  • When facing patients with rare diseases, it is important to learn to admit your ignorance and, time permitting, to offer to look for an answer some time later.

General and disease-specific information on rare diseases

WebsiteDescriptionAddress
EURORDIS - Rare Diseases EuropeAn alliance of rare disease patient organisations in Europewww.eurordis.org http://www.eurordis.org
OMIM - Online Mendelian Inheritance in ManA genetic disorders databasewww.omim.org http://www.omim.org/
OrphanetThe most comprehensive European website on rare diseases and orphan drugs
www.orpha.net http://www.orpha.net

Rare diseases in national health care

  • A national (or regional) programme for rare diseases may be available, defining the aims and organization of care for rare diseases. Find out whether a relevant programme exists.
  • Patient organizations associated with various rare diseases offer experiential knowledge and peer support for patients and families, for example. Find out about local availability.
  • ERN centres are each responsible for specialized care of certain specialties, obtaining support from ERN networks, as necessary.
  • Primary health care and social services play a very important role in patients' daily lives.

New drugs and treatments

  • The diagnosis of rare diseases has developed significantly over the last few decades, and in the best case the diagnosis can be confirmed relatively quickly. However, new drugs and targeted treatments are available for only a small share of rare diseases.
  • Further development of gene technology brings new hope for some diseases, whereby a faulty gene can be replaced with a normally functioning gene.
    • This is understandably only possible for diseases where tissues that play a key role in the disease can be reached for genetic correction.
    • In some haematological disorders, for example, treatment is technically possible because bone marrow cells are available for such treatment. However, correcting gene defects in brain cells, for instance, would be highly challenging.
  • In some diseases, faulty gene function will have caused irreversible damage at a very early stage, often during foetal development, already, and this cannot be corrected.

ORPHAcodes

  • European countries will within a few years start using ORPHAcodes, meaning that each rare disease will be entered in patient documents by its specific code and not just as belonging to a group of diseases http://www.orphadata.com/orphanet-nomenclature-for-coding/.
  • Most rare diseases are chronic, and a code once entered for a patient will facilitate monitoring his/her situation in health care registers even if the code is not re-entered at every visit.
  • The codes will provide information about the aetiology of the disease and about the levels of health care and centres that patients are referred to.
  • ORPHAcodes can be launched as soon as patient record systems are ready for this.
  • Later on, necessary guidance and training will be needed, first for the professionals who are in the most central position for the diagnosis of rare diseases, such as clinical geneticists and paediatricians.

    References

    • European Reference Networks (ERN) http://health.ec.europa.eu/european-reference-networks_en
    • Tambuyzer E, Vandendriessche B, Austin CP, et al. Therapies for rare diseases: therapeutic modalities, progress and challenges ahead. Nat Rev Drug Discov 2020;19(2)93-111. [PubMed]
    • Casali PG, Trama A Rationale of the rare cancer list: a consensus paper from the Joint Action on Rare Cancers (JARC) of the European Union (EU). ESMO Open 2020;5(2). [PubMed]
    • Nguengang Wakap S, Lambert DM, Olry A, et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet 2020;28(2)165-173. [PubMed]
    • Ferreira CR The burden of rare diseases. Am J Med Genet A 2019;179(6)885-892. [PubMed]

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