Commonly Used Terms In Rare Disease
Navigating rare disease information, resources and services can be overwhelming. Below are some commonly used terms in rare disease.
A list of regulatory and independent expert bodies involved in health technology assessments (decision making) for the reimbursement of medicines, treatments and medical technologies, can be found at National Services: Health Technology Assessment on the RARE Portal.
Chronic conditions are used interchangeably with ‘chronic diseases’, ‘noncommunicable diseases’, and ‘long term health conditions’. Chronic conditions have complex and multiple causes; may affect individuals either alone or as co-morbidities; usually have a gradual onset, although they can have sudden onset and acute stages; occur across the lifespan, although they become more prevalent with older age; can compromise quality of life and create limitations and disability; are long-term and persistent, and often lead to a gradual deterioration of health and loss of independence. While not usually life-threatening, chronic conditions are the most common and leading cause of premature mortality.1
Disability is defined by the Disability Discrimination Act 1992 (Cth) as2:
- total or partial loss of the person’s bodily or mental functions;
- total or partial loss of a part of the body;
- the presence in the body of organisms causing disease or illness;
- the malfunction, malformation or disfigurement of a part of the person’s body;
- a disorder or malfunction that results in the person learning differently from a person without the disorder or malfunction; and
- a disorder, illness or disease that affects a person’s thought processes, perception of reality, emotions or judgement, or that results in disturbed behaviour.
Diagnostic odyssey refers to the significant diagnostic delay and misdiagnosis that is commonly faced by people when trying to achieve a diagnosis for a medical condition.3
DNA (deoxyribonucleic acid) contains the information for making and maintaining all living things, including people.4
Epidemiology is the study of how often diseases occur in different groups of people and why. Epidemiological information is used to plan and evaluate strategies to prevent illness and as a guide to the management of patients in whom disease has already developed.5
Genes are ‘the instructions for building our body and telling it how to work’.6 Genes are located on chromosomes – we normally have 46 chromosomes that are in pairs (for each of the 23 pairs, we get one from our mother and one from our father). Our entire genetic code is called a genome.
Genetics is ‘the study of how genes work and transmit information from parents to offspring. It can help us understand the risk of inheriting a genetic disease’.7
Genetic counselling ‘involves talking about a genetic condition with a health professional who has qualifications in both genetics and counselling.Genetic counselling can help you understand more about an inherited condition (a condition passed down from one or both parents) and what causes it. A genetic counsellor can talk you through genetic testing. They can also help you and your family adjust to living with a genetic condition and plan for the future’.8
Genetic counsellors are ‘allied health professionals who work as part of a skilled team delivering personalised information and risk assessments to patients and their families with, or at risk of genetic conditions. Genetic counselling is the process of helping people understand and adapt to the medical, psychological, and familial implications of the genetic contributions to disease. The role of a genetic counsellor allows individuals to make informed decisions about their health’. 9 In Australia, ‘the education, training, and certification of genetic counsellors is administered by the Human Genetics Society of Australasia (HGSA) Board of Censors for Genetic Counselling, and is governed by the HGSA Code of Ethics and Scope of Practice for Genetic Counsellors’.10
Genetic testing ‘investigates variants in our genes, chromosomes, or proteins. A genetic test might investigate a single gene, search for large changes or rearrangements in our chromosomes or analyse the proteins formed from genes. Genetic testing also encompasses newer forms of investigations called genomic testing’.6
Genetic variants are ‘changes in our genes that contribute to our uniqueness’.6 Most genetic differences have no impact on our health but there are some variants (often known as a pathogenic variant mutation) that can cause disease. Health conditions that are caused by genetic variants are called ‘genetic conditions’.11
Genetic variant of uncertain significance is a genetic variant identified in the DNA of an individual with a health condition but it is not yet known if the variant causes or contributes to that health condition.11
Genomics is ‘the study and mapping of genomes – the full set of genetic instructions for an organism. It includes both human and other genomes and how these interact with the environment. Genomics can help doctors identify and diagnose genetic disorders and rare diseases, develop prevention strategies and tailor a patient’s treatment’.7
Genomic testing allows the investigation of vast amounts of the genetic sequence (testing of many genes or the entire genome) at once. This is used when there are several genes associated with a condition, or when the causal gene is unknown.6
Health technology is ‘a broad term meaning something that is intended to do any of the following: prevent, diagnose or treat medical conditions, promote health, provide rehabilitation, and organise delivery of health care. Health technologies include tests, medical devices, medicines, vaccines, blood products, procedures, and programs or systems involved in health care’.12
Health Technology Assessment (HTA) is ‘the multidisciplinary field of policy analysis that studies medical, social, ethical, and economic implications of the development, diffusion, and use of health technologies’.13 HTA encapsulates a range of processes and mechanisms that use scientific evidence to assess the quality, safety, efficacy and cost effectiveness of new medicines and technologies before they are made available in Australia (for example, medicines being funded under the Pharmaceutical Benefits Scheme).
Incidence – The incidence of a disease is the rate at which new cases occur in a population during a specified period.14
ORPHAcodes are the Orphanet nomenclature of rare diseases – a unique, time-stable and non-reusable numerical identifier for a rare disease.They are recognised as the most appropriate nomenclature for clinical coding of rare diseases in Europe.15 The World Health Organisation (WHO) is collaborating with Orphanet to map Orphacodes to the International Classification of Diseases (ICD).16
Orphan drugs ‘are so called because they are intended to treat diseases so rare that sponsors are reluctant to develop them under usual marketing conditions. The indications of a drug may also be considered as ‘orphan’ since a substance may be used in the treatment of a frequent disease and not have been intended for another, more rare indication’.17
Peer support ‘is a system of giving and receiving help founded on key principles of respect, shared responsibility, and mutual agreement of what is helpful. Peer support is not based on psychiatric models and diagnostic criteria. It is about understanding another’s situation empathically through the shared experience of emotional and psychological pain. When people find affiliation with others they feel are ‘like’ them, they feel a connection. This connection, or affiliation, is a deep, holistic understanding based on mutual experience where people are able to ‘be’ with each other without the constraints of traditional (expert/patient) relationships’.18
Person-centred and family-centred care are terms used throughout the National Strategic Action Plan for Rare Diseases (the Action Plan)3 to refer to care that sees an equal partnership between the person receiving care, their family (if appropriate), carers and health professionals to ensure that health care decisions are respectful of and responsive to the preferences, needs and values of people, and that they have the education and support they need to make decisions and participate in their own care.
Phenotype is a term that refers to ‘the observable physical properties of an organism… [including its] appearance, development and behavior. Examples of phenotypes include height, wing length, and hair colour. Phenotypes also include observable characteristics that can be measured in the laboratory, such as levels of hormones or blood cells’.19
Precision medicine is an emerging approach for disease prevention and management that tailors care to account for an individual’s variations in genes, environment, and lifestyle.20
Prevalence – The prevalence of a disease is the proportion of a population with a disease at a point in time (point prevalence) or over a specified period of time (period prevalence).21
Primary health care – ‘In Australia, primary health care is typically the first contact an individual with a health concern has with the health system. Primary health care covers health care that is not related to a hospital visit, including health promotion, prevention, early intervention, treatment of acute conditions, and management of chronic conditions. Primary health care services are delivered in settings such as general practices, community health centres, allied health practices, and via communication technologies such as telehealth and video consultations. General practitioners (GPs), nurses, nurse practitioners, allied health professionals, midwives, pharmacists, dentists, and Aboriginal health practitioners are all considered primary health care professionals’.22
Prevention, when referring to disease, includes the actions aimed at avoiding the manifestation of a disease as well as the early detection when this improves the chances for positive health outcomes.23 Examples in the National Strategic Action Plan for Rare Diseases3 include:
- Pre-conception vaccination against chicken pox (varicella) to avoid development of the rare disease congenital varicella syndrome in infants;
- Awareness and education targeted at families of pregnant women around the risks of passing whooping cough, a rare disease, onto newborns, and measures to reduce those risks (i.e. vaccination);
- Folic acid fortification and supplementation to lower the incidence of rare neural tube defects, such as spina bifida, and;
- Prenatal and newborn screening programs to enable early detection of rare diseases.
Public health surveillance is ‘the continuous, systematic collection, analysis and interpretation of health-related data. Disease surveillance data serves as an early warning system for impending outbreaks that could become public health emergencies; enables monitoring and evaluation of the impact of an intervention, helps track progress towards specified goals; and monitors and clarifies the epidemiology of health problems, guiding priority-setting and planning and evaluation public health policy and strategies’.24
Rare diseases – A disease is considered rare if it affects fewer than, or equal to, 5 in 10, 000 people. Approximately eight per cent of Australians live with a rare disease3. Extrapolated to an Australian population of over 25 million people25, this equates to around two million Australians.
There are at least 7, 000 known rare diseases, with 80 per cent of genetic origin.3 Types of non-genetic rare diseases include rare infectious diseases, rare autoimmune diseases and rare cancers.3,26
A disease may be considered rare in one region of the world but not in another. Current knowledge and data of rare diseases in Australia are too limited to make these distinctions.
Rare diseases, like many other chronic diseases, are often serious and progressive. They typically display a high level of symptom complexity and thus are a significant cause of ongoing health and psycho-social challenges. Fewer than 5% of rare diseases have an approved treatment, so improving quality of life and extending life expectancy of people living with a rare disease relies on appropriate treatment and care.People living with a rare disease face common challenges including difficulty obtaining an accurate diagnosis, lack of treatment options and inadequate, fragmented care. 3,26
Registries are collections of standardised information about a group of patients who share a condition or health experience. Registries serve a variety of purposes, including epidemiological surveillance, evaluation of disease outcomes and treatments, and facilitating patient access to clinical trials and novel therapies.27
Research is defined as the creation of new knowledge and/or the use of existing knowledge in a new and creative way to generate new concepts, methodologies and understandings. This could include synthesis and analysis of previous research to the extent that it leads to new and creative outcomes.28
Telehealth involves the remote consultation of a healthcare provider (by phone or video call) when they have determined that a physical examination isn’t needed, or when the patient is unable to see them in person. This can be for diagnosis, treatment and prevention purposes.29
Transition is the term used throughout the Action Plan to refer to the transition of one’s care from one health service to another.3 This may be due to a change in age, level of needs, providers, geography or other factors. The transition from paediatric to adult health services is commonly cited as a challenge for people living with a rare disease.
Undiagnosed population ‘involves the different groups of undiagnosed patients, as based upon the various reasons for difficulties in obtaining a diagnosis’:
- Not yet diagnosed. This refers to a ‘patient who lives with an undiagnosed condition that should be diagnosed but hasn’t been because the patient has not been referred to the appropriate clinician due to common, misleading symptoms, or an unusual clinical presentation of a known rare condition’; and
- Undiagnosed or Syndromes Without A Name (SWAN). This refers to a ‘patient for whom a diagnostic test is not yet available since the disease has not been characterised and the cause is not yet identified. This patient can also be misdiagnosed as his/her condition can be mistaken for others. These conditions are also likely to be rare.’30
- Australian Health Ministers’ Advisory Council. National Strategic Framework for Chronic Conditions. Commonwealth of Australia. Canberra; 2017. Available from: https://www.health.gov.au/sites/default/files/documents/2019/09/national-strategic-framework-for-chronic-conditions.pdf
- Disability Discrimination Act 1992 (Cth). Available from: https://www.legislation.gov.au/Details/C2022C00367
- Commonwealth of Australia. Department of Health. National Strategic Action Plan for Rare Diseases. Canberra; 2020. 63 p. Available From: https://www.health.gov.au/sites/default/files/documents/2020/03/national-strategic-action-plan-for-rare-diseases.pdf
- Fact sheet 01: An Introduction to DNA, RNA, Genes and Chromosomes. 2021. The Centre for Genetics Education. 4 p. Available from: https://www.genetics.edu.au/PDF/DNA_RNA_genes_and_chromosomes_fact_sheet-CGE.pdf
- Coggon D, Rose G, Barker DJP. Chapter 1: What is epidemiology? in: Epidemiology for the Uninitiated. 4th ed. The BMJ [Internet]. 1997. Available from: https://www.bmj.com/about-bmj/resources-readers/publications/epidemiology-uninitiated/1-what-epidemiology
- Australian Genomics. About Genomics. Accessed March 29, 2023. https://www.australiangenomics.org.au/about-genomics/
- Commonwealth of Australia. Department of Health and Aged Care. Genetics and genomics. Accessed June 5, 2023. https://www.health.gov.au/topics/genetics-and-genomics
- Pregnancy, Birth and Baby. Genetic Counselling. Accessed June 5, 2023. https://www.pregnancybirthbaby.org.au/genetic-counselling
- NSW Health. A career as a genetic counsellor. Accessed June 5, 2023. https://www.health.nsw.gov.au/careers/students/Pages/careers-genetic-counsellor.aspx
- Human Genetics Society of Australasia (HGSA). Genetic Counselling Training and Accreditation. Accessed June 5, 2023. https://www.hgsa.org.au/Web/Web/ET/Genetic-Counselling.aspx?hkey=975b23ce-fa8e-485a-a7ee-fc88aab9a60d
- Variant of Uncertain Significance (VUS). 2021. The Centre for Genetics Education. 2p. Available from: https://www.genetics.edu.au/PDF/Variant%20of%20Uncertain%20Significance.pdf
- Commonwealth of Australia. Department of Health and Aged Care. About health technologies and digital health. Accessed March 28, 2023. https://www.health.gov.au/topics/health-technologies-and-digital-health/about
- Fattore G, Maniadakis N, Mantovani LG, Boriani, G. Health technology assessment: What is it? Current status and perspectives in the field of electrophysiology. EP Europace [Internet]. 2011; 13(2):ii49-ii53. Available from: https://doi.org/10.1093/europace/eur083
- Coggon D, Rose G, Barker DJP. Chapter 2: Quantifying disease in population in: Epidemiology for the Uninitiated. 4th ed. The BMJ [Internet]. 1997. Available from: https://www.bmj.com/about-bmj/resources-readers/publications/epidemiology-uninitiated/2-quantifying-disease-populations
- RD-Code. Introduction. Accessed June 5, 2023. https://www.rd-code.eu/introduction/
- World Health Organization. Webinar on ICD-11 use for Rare Diseases. Accessed June 5, 2023. https://www.who.int/news-room/events/detail/2022/09/27/default-calendar/webinar-on-icd-11-use-for-rare-diseases
- Orphanet. About Orphan Drugs. Accessed March 28, 2023. https://www.orpha.net/consor/cgi-bin/Education_AboutOrphanDrugs.php?lng=EN
- Mead S, Hilton D, Curtis L. Peer Support: A Theoretical Perspective. Psychiatr. Rehabil. J. 2001; 25(2):134- 41.
- Nature Education (2014) Phenotype / phenotypes in: Scitable by Nature Education [Internet]. Accessed March 28, 2023. Available from: https://www.nature.com/scitable/definition/phenotype-phenotypes-35/
- MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2022 May 17]. What is precision medicine? Accessed March 28, 2023. Available from: https://medlineplus.gov/genetics/understanding/precisionmedicine/definition/
- McNutt L, Krug A. Prevalence (epidemiology) in: Encyclopaedia Brittanica [Internet]. Accessed March 28, 2023. Available from: https://www.britannica.com/science/prevalence
- Commonwealth of Australia. Australian Institute of Health and Welfare. Primary health care in Australia. [updated 2016 May 24]. Available from: https://www.aihw.gov.au/reports/primary-health-care/primary-health-care-in-australia/contents/about-primary-health-care
- World Health Organization. WHO Regional Office for the Eastern Mediterranean: About us. Accessed March 28, 2023. https://www.emro.who.int/about-who/public-health-functions/health-promotion-disease-prevention.html
- World Health Organization. Public health surveillance. Accessed March 28, 2023. https://www.who.int/emergencies/surveillance
- Australian Bureau of Statistics. National, state and territory population: Statistics about the population and components of change (births, deaths, migration) for Australia and its states and territories (reference period: September 2022) [Internet]. 2023. Available from: https://www.abs.gov.au/ausstats/abs@.nsf/mf/3101.0
- Orphanet. About Rare Diseases. Accessed March 28, 2023. https://www.orpha.net/consor/cgi-bin/Education_AboutRareDiseases.php?lng=EN
- Workman TA. Engaging Patients in Information Sharing and Data Collection: The Role of Patient-Powered Registries and Research Networks [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013. Defining Patient Registries and Research Networks [cited 2023, 29 March]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK164514/
- Western Sydney University. Definition of Research. Accessed March 28, 2023. https://www.westernsydney.edu.au/research/researchers/preparing_a_grant_application/dest_definition_of_research
- Commonwealth of Australia. Department of Health and Aged Care. Telehealth. Accessed March 28, 2023. https://www.health.gov.au/topics/health-technologies-and-digital-health/about/telehealth
- SWAN UK, Wilhelm Foundation, EURODIS, Rare Voices Australia, Canadian Organization for Rare Disorders, Advocacy Service for Rare and Intractable Diseases’ stakeholders in Japan, National Organization for Rare Disorders. International joint recommendations to address the specific needs of undiagnosed rare diseases patients. Oct 2016. 12p. Available from: https://download2.eurordis.org/documents/pdf/Undiagnosed-International-Joint-Recommendations.pdf