Rare diseases: A common challenge

Saturday 29 February 2020 is Rare Disease Day. Held on the last day of February each year, this event is now in its twelfth year and aims to raise awareness of rare diseases. This campaign targets not only the general public but also policymakers and decision-makers, and aims to work towards ‘more equitable access to diagnosis, treatment, care and social opportunity’ for patients across the spectrum of rare diseases [1].

Rare diseases are defined in the European Union as diseases that affect fewer than 1 in 2,000 individuals, and in the US as diseases that affect fewer than 200,000 people in the total US population [2]. Over 6,100 unique rare diseases are recognised by Orphanet – an online resource that catalogues information with the aim of improving rare disease diagnosis and care [3]. Although these disorders are, by definition, rare, it’s estimated that between 263 million and 446 million people worldwide have a rare disease [4]. This means that in our global population of approximately 7.7 billion, rare diseases affect between 3.4% and 5.7% of people [5]. Indeed, according to 2019 figures from the United States Census Bureau, if rare diseases were a country, its population would be the 3rd or 4th largest in the world, roughly the size of the US [6]. Put into these terms, rare diseases seem a lot less ‘rare’.

As the term ‘rare disease’ covers such a large number of disorders, there is a vast heterogeneity of signs and symptoms. Although the majority of rare diseases have a genetic basis and symptoms that are present from childhood [4], such diseases can present at any age. Signs and symptoms can be non-specific, complex and progressive, and affect multiple organ systems simultaneously. Some rare diseases are even highly heterogeneous between patients; this might be because of differences in causative mutations, but in other cases the reasons are not currently understood. Prompt and accurate diagnosis is essential for optimal management of rare diseases, yet, given the enormous variability, this is not always a straightforward process and providing individualised care may seem a challenging concept. However, with diagnostic and treatment advances, and disease awareness campaigns, steps are being taken to reach the goal of identifying patients at an early stage of disease and supporting them throughout their lives.

The availability of diagnostic tests and screens has increased rapidly – 10 new tests entered the market each day in a study published in 2018 [7]. However, the key challenge is in understanding which of the available options to use: if a patient has non-specific or subtle presenting symptoms, it may be unclear which of the available single gene tests, genetic screens or metabolite assays to choose. Therefore, selecting a diagnostic test for a particular patient may be challenging, and high costs may prevent the use of multiple tests.

To help combat this, resources to aid differential diagnoses are available. For example, in addition to cataloguing information about rare diseases, Orphanet offers directories of experts, specialist centres and laboratories that can support with diagnoses [2]. Online resources and apps, such as ‘Figure 1’, allow clinicians to share cases with over 2.5 million other healthcare professionals who can collectively provide multidisciplinary expert advice [8]. These resources provide vital learning opportunities, allowing clinicians to stay informed about rare therapy areas that are not routinely seen in their clinics. For clinicians working in the field of rare diseases, in which the number of affected patients may be fewer than 10 cases around the globe [9], the ability to communicate with other clinicians who can assist in diagnosis and treatment can be invaluable. For patients with a severe, rapidly progressive rare disease, these diagnostic platforms have an enormous potential to contribute to prompt, accurate diagnosis and, consequently, optimal patient care.

Historically, diagnostic delays for patients with rare diseases have been associated with limited disease awareness among clinicians, particularly when faced with patients in early disease stages. The increasing number and accessibility of diagnostic platforms and global resources provides opportunities to continue to reduce these delays and ensure prompt diagnosis and appropriate treatment, regardless of disease prevalence. Rare Disease Day has a key role in raising awareness about rare diseases and ensuring that they are kept in mind every day and considered alongside more common disorders so that the aim of ‘more equitable access to diagnosis, treatment, care and social opportunity’ for those living with a rare disease is achieved [1].

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  1. Rare Disease Day. 100 days until Rare Disease Day 2020! Available at National Center for Advancing Translational Sciences. FAQs about rare diseases. Available at: https://www.rarediseaseday.org/page/news/100-days-until-rare-disease-day-2020. Accessed February 2020.
  2. National Institutes of Health. FAQs about rare disease. https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases. Accessed February 2020.
  3. The portal for rare diseases and orphan drugs. Available at: https://www.orpha.net/consor/cgi-bin/index.php. Accessed February 2020.
  4. 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.
  5. United Nations. Population. Available at: https://www.un.org/en/sections/issues-depth/population/index.html. Accessed February 2020.
  6. United States Census Bureau. U.S. Census Bureau current population. Available at: https://www.census.gov/popclock/print.php?component=counter. Accessed February 2020.
  7. Phillips KA, Deverka PA, Hooker GW et al. Genetic test availability and spending: Where are we now? Where are we going? Health Aff (Millwood) 2018; 37 (5): 710–716.
  8. Figure 1. Available at: https://www.figure1.com/. Accessed February 2020.
  9. Orphanet Report Series: Rare Diseases Collection. Prevalence and incidence of rare diseases: Bibliographic data. Available at: https://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_pdf. Accessed February 2020.