Rare disease day was first celebrated in 2008, on February 29 – a rare day. Since then, it is celebrated each year on the last day of February. It’s a day to spread awareness about rare diseases, and receive support from the public that is invaluable in bridging health and social care. Although individual diseases may be rare and the number of people affected by each disease may be few, the total number of patients affected by rare diseases globally is estimated to be more than 350 million – more than cancer and AIDS combined1.

Worldwide, there are over 7,000 rare diseases1. Contrary to infectious diseases or birth defects, most rare diseases are not tracked. Consequently, the exact number of rare diseases is difficult to pinpoint, and an official ‘rare list’ recording the frequency order of each disease doesn’t exist. In Europe, a disease is termed rare if it occurs in less than 1 in 2,000 people. In the US, where rare diseases are also called ‘orphan diseases’ due to the drug companies’ lack of interest in developing treatments for them, a disease is called ‘rare’ if fewer than 200,000 Americans are affected by it at any time. Accordingly, there is a very broad frequency range of rare diseases; Trisomy 18 is considered rare, with a 1 in 5,000 incidence2, along with Progeria that has a 1 in 4 to 8 million reported incidence3. Epidemiological prevalence of rare diseases is also interesting. B-Thalassemia has a global incidence of 1 in 100,000, yet its incidence in the Mediterranean population is 1 in 10,0004,5. Likewise, Tay-Sachs is very rare in the general population, with a 1 in 320,0004 prevalence, yet it affects 1 in 3,200 Ashkenazi-Jews6.

Diagnosis of rare diseases is challenging due to the diversity and variability of symptoms among diseases and patients. On average, it takes 8 years for an accurate diagnosis to be made1. Management of symptoms and treatment choices are limited for most rare diseases, with 95% of them not having an FDA-approved treatment1. Medically and socially, there is lack of information on the rarest diseases, which can be challenging. A great part can be mitigated by support groups and online platforms of patients and family members that have a personal experience with the condition, and can offer advice and knowledge on management, clinical trials and experts in the field.

Rare diseases can manifest from infections or environmental causes, or they are presently classified as ‘rare’ due to healthcare advances – smallpox and polio are now rare diseases due to vaccinations. 80% of rare diseases have genetic origins, caused by single genes, chromosomal or multifactorial reasons1.

Fanconi anemia (FA) is a rare, hereditary disease that occurs relatively equally in all ethnic groups and sexes3, with a frequency rate of 1 in 160,0002. Manifesting in childhood – where more than half of the diagnoses are made7 – symptoms vary from physical abnormalities, like small head and skin pigmentation, to bone marrow failure. The genes responsible for causing FA are estimated to be more than 18. As these genes are responsible for repairing DNA damage, faulty changes (mutations) in these prevent them from performing their normal actions, and lead to accumulated DNA damage. In turn, this disrupts the normal functions of the bone marrow, upsets the production of platelets, white and red blood cells, and ultimately raise the patients’ risk of excessive bleeding, infections, and blood cancer3,7.

Gracile syndrome is a rare, inherited metabolic disease. Its name stands for the disease symptoms and characteristics – Growth Retardation; Aminoaciduria – the increased amount of amino acids in the urine; Cholestasis – the decreased flow of bile that causes indigestion; Iron overload; Lactacidosis – the build-up of lactate that affects the liver and kidneys; and Early death. It is almost exclusively found in Finland, occurring in 1 in 50,000 individuals, with the prevalence in the general population being less than 1 in 1,000,0004. Affected newborns are smaller than average, fail to thrive and exhibit serious liver and kidney problems within the early months of life. Gracile syndrome follows an autosomal recessive pattern, so both parents need to be carriers for the baby to be affected. Unfortunately, there is no cure for Gracile Syndrome, and most babies die by 4 months of age3. Early diagnosis – which can be achieved by NIPT – is invaluable for managing clinical care and symptomatic treatment, and improving quality of life. The mutation that causes Gracile Syndrome prevents the gene from converting energy from food sources into a form that cells can use, so patients are depleted of energy3.

Maple Syrup Urine Disease (MSUD) takes its name from the sweet odor of affected infants’ urine. It is a rare, autosomal recessive disorder occurring in less than 1 in 185,000 individuals globally2. Symptoms vary depending on disease severity, and can appear from the first days of life. They include failure to thrive, drowsiness, progressive lethargy and when left untreated, brain damage; eventually leading to coma and respiratory failure within the first month of life4. This time-sensitive disorder can be detected prenatally via NIPT, ensuring prompt clinical management of symptoms that may be life-saving, with episodes of metabolic crises occurring when triggered. MSUD results after mutations in three genes, involved in breaking down toxic byproducts, prevent them from performing their actions. This results in excess amount of acid in the body that disturbs the body’s metabolic processes.

The 350 million people affected by rare diseases are patients that deserve proper diagnosis, care and treatment. The public, decision-makers and the healthcare industry can drive action that will benefit patients. On a political level, the ‘Orphan Drug Act’ US Congress enforced in 1983 provided financial incentive to pharmaceutical companies to encourage them to research into and develop drugs for rare diseases. In the science field, international research, linking experts and combining knowledge and funds across the world can have a positive impact in patients’ lives.

To check for the rare diseases that VERAgene can detect, please visit https://www.nipd.com/monogenic-disorders

References:

  1. Global Genes, ‘Rare Facts’ (2015) https://globalgenes.org/rare-facts/
  2. Genetics Home Reference (2019) https://ghr.nlm.nih.gov/
  3. Genetic and Rare Diseases Information Center, https://rarediseases.info.nih.gov/
  4. Orphanet (2019), https://www.orpha.net/consor/cgi-bin/index.php?lng=EN
  5. Galanello R. and Origa R. (2010), ‘Beta-thalassemia’, Orphanet Journal of Rare Diseases, 5:11
  6. Rozenberg R. and Pereira Lda V. (2001). ‘The frequency of Tay-Sachs disease causing mutations in the Brazilian-Jewish population justifies a carrier screening program’. Sao Paulo Medical Journal, 119(4): 146-149.
  7. National Organization of Rare Disorders (2019) https://rarediseases.org/rare-diseases