Rare Diseases: Everything you need to know

In the UK alone, it’s estimated that around 3 million people are living with a rare disease or condition. The effects of these diseases can be wide-ranging and unique, meaning that many of these 3 million people will face challenges the majority of the population are likely never to experience. 

There are some conditions where little is known about what causes them, and more importantly, how they can be treated. This is why studies and research into rare diseases are so important, as well as support and understanding for those that live with them.

As experts in rare disease clinical trials, we are keen to raise more public awareness about what rare diseases are, and what it means to live with them. We have compiled some key information and facts about rare diseases, which we hope you will find helpful if you would like to learn more. 

What is a rare disease?

According to research conducted by the European Union, for a disease to be considered ‘rare’, it must affect no more than 1 in 2000 people; the equivalent to 0.05% of a population, or lower. However, the definition of a rare disease can vary within the global science community. For instance, according to excerpts from the Orphan Drug Act of 1983, a rare disease in the United States is one which affects “less than 200,000 persons in the United States”.

Based on the current population of the US, this would include any disease which affects less than 1 person in 13,950 (or below 0.01% of the population). 

It’s estimated that 1 in 4 people in the UK suffers from hay fever (approximately 25% of the population), making it one of the most common conditions in the UK. 

However, conditions like Prader-Willi syndrome, which affects between 1500-2000 people in the UK, would fit the criteria of a rare disease or condition in the EU. Based on these figures, it affects only 1 in 33,000 people in the UK (0.03% of the population).

What is an orphan disease?

The term ‘orphan diseases’ is sometimes used interchangeably with the term rare disease. An orphan disease may have a number of shared characteristics with other rare diseases, such as difficulty accessing treatment and a lack of resources for research. However, in the US and the EU, orphan disease has a distinct legal meaning.

To again reference the Orphan Drug Act of 1983, orphan diseases may be rare, but are specifically diseases “for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will [be] recovered from sales in the United States of such drug”. Simply, these diseases have been identified as costly to treat, because revenue generated by the sales of a drug to treat them would be unlikely to recoup the costs incurred by developing and distributing it.

However, the Orphan Drug Act of 1983 was developed to address this issue, and was a law passed to encourage and facilitate the production of orphan drugs to treat rare — and non-rare diseases. For instance, this law could support those suffering with Neglected Tropical Diseases (NTDs) like rabies and leprosy, which are rare in western countries, but very common in third-world countries where resources are scarce.

Diagnosing rare diseases

As you might imagine, one of the main challenges faced by those suffering from a rare disease can be getting a diagnosis. When a disease or condition has only just started to be reported, or affects a very small number of people, it can be hard for doctors to diagnose it. 

If there is little literature, research, or awareness around a condition, then not every doctor may know of its existence — particularly if it is most prevalent in a specific area of the world. 

Besides this, there can be a number of other obstacles patients face when seeking a diagnosis.


When patients present with a rare disease or condition, particularly if they have been living with the symptoms for a long time, they may not recognise or list every symptom. 

However, even the smallest symptom could be the catalyst for their doctor to investigate a particular rare condition. Something as minor as an oddly-shaped rash or sore throat, whilst enough to be overlooked by the patient, may be the missing piece in the puzzle of what is causing their symptoms. 

This is why doctors encourage patients to be thorough when listing their symptoms, even if at the time they may seem insignificant.


Unfortunately, a number of diseases and conditions share common symptoms with one another. This is another reason why it’s so important for medical professionals to have a full and complete understanding of your current symptoms and your medical history. 

There are some conditions which are notoriously hard to diagnose, because they closely mimic the symptoms of other, more well-known illnesses. For example, Lyme Disease shares a number of common symptoms with Chronic Fatigue Syndrome, Fibromyalgia, and even depression. 

In 2017, there were 1534 reported cases of Lyme disease in the UK, but experts believe the true number of instances could be much higher due to the difficulties faced with diagnosing the disease. It can be frustrating for patients, but doctors must sometimes go through a process of eliminating similar possibilities before they can arrive at the correct diagnosis. 

Rare Diseases and Zebras

While researching rare diseases, particularly in online communities, you may come across the term “zebra”, and wonder what these animals have to do with uncommon health conditions. This term is often used to refer to those with Ehlers-Danlos Syndromes — a group of conditions which affect the connective tissues around the skin, joints, and internal organs. 

Classical Ehlers-Danlos syndrome is estimated to affect about 1 in 20,000 people, fitting both the EU and US definitions of a rare disease. It is characterized by joint hypermobility, weak muscle tone, and extremely stretchy, but fragile skin. Because of the wide range of ways in which the symptoms can present themselves, Ehlers-Danlos syndromes are sometimes misdiagnosed as similar disorders. 

The nickname “zebras” was coined in response to a phrase that’s purported to be common amongst people studying medicine. The phrase is:

“When you hear the sound of hooves, think of horses — not zebras.”

What this phrase implies is that medical practitioners should not look for the unexpected when treating patients, as the simplest reason for their ailment is most likely to be the correct one. However, when it comes to the treatment of rare diseases, it’s clear how this philosophy could be harmful.  

This is why those with Ehlers-Danlos syndromes identify themselves as ‘zebras’, knowing that the rarity of their condition and the way in which symptoms present could be considered ‘unexpected’. The use of the phrase is satirical, as many health activists recognise the importance of raising awareness about rare diseases. 

Awareness of rare diseases not only helps patients to recognise and more accurately report their symptoms, but encourages medical professionals to keep an open mind when diagnosing their patients. The most simple explanation may not always be the right one, and closing ourselves off from other possibilities can be dangerous — particularly in the practice of medicine.

When is Rare Disease Day?

Rare Disease Day takes place annually on the last day of February. 

On this day, events are held at the local and global level to raise awareness and support people affected by rare diseases. This is due to the fact that they will often face challenges that other members of the population, even those living with other, more common conditions, may not. 

We have already touched on the difficulties that can be faced when getting a diagnosis. However, those with rare diseases may also struggle with:

Lack of resources and support

If you suffer from a very rare disease, doctors who specialise in it may be few and far between. Some patients have to travel long distances in order to undertake the treatment they need, and may not be able to benefit from things that others take for granted, such as specialist support groups or literature.

Depending on the symptoms of their condition, regular travel can also put greater strain on them, meaning they face greater risks while seeking out treatment. 

Stigma and discrimination

If a symptom, or group of symptoms, is unfamiliar to people, they may have less understanding when they encounter somebody that has them. 

For instance, most people are aware of Tourette’s syndrome, a condition which affects 0.6% of the population and causes people to make involuntary sounds and movements. Therefore, if they see somebody exhibiting these behaviours, they may have an idea as to why and are more likely to be empathetic.

However, Prader-Willi Syndrome, a rare condition mentioned above, is less well-known but also involves challenging behaviours like compulsive overeating and temper tantrums. Without understanding much about the condition, the same people who would show empathy to a child with Tourette’s syndrome, may react poorly to one displaying the behaviours associated with Prader-Willi syndrome.

Limited research or studies conducted into their condition

It’s an unfortunate fact that the fewer people a condition affects, the harder it can be to fund research into causes, symptoms, and treatment. Even with the best efforts of medical researchers and fundraising organisations, even fully funded studies can come up against a number of problems.

If a disease only affects a small number of people, it can be difficult to secure participants for studies. Small sample sizes, coupled with the fact that everybody may experience the symptoms differently, can make research into rare diseases difficult. 

But despite this, a number of successful clinical studies are carried out in the field of rare diseases every year. Though there may be greater challenges to overcome, any understanding that can be brought to these conditions — some of which we know so little about — can be extremely impactful. 

How many rare diseases are there?

According to the European Commission, there are between 6000 and 8000 rare diseases which affect an estimated 30 million people within the European Union. 

However, as the definition of a rare disease can differ globally, the estimated number that exists will differ from country to country as well. Statistics from the National Institutes of Health (NIH) estimate that there are around 7000 known rare diseases in the United States, affecting between 25 and 30 million Americans.

But it is also important to bear in mind that not all rare diseases are deadly or contagious. Some of these statistics may seem frightening, but people who have rare diseases often face those who have uninformed opinions regarding their conditions. For instance, that they have no quality of life, that their illness will be fatal, or that somebody else could catch it.

Rare diseases are as varied in severity and symptoms as the individuals who have them, which is another point that rare disease activists would like more people to understand.

What are some examples of rare diseases?

There are thousands of rare diseases and conditions, which cover a broad spectrum. They affect different parts of the body, present different symptoms, and the ways in which they affect individuals are bound to be different as well.

Here are five examples of diseases and conditions that fit the EU definition of a rare disease, meaning that they affect fewer than 1 in 2000 people.

1. Cystic Fibrosis

Cystic Fibrosis (CF) is a genetic condition affecting about 1 in every 2500 people in the UK. CF causes a production of sticky mucus which builds up in the lungs and digestive system, which can lead to severe respiratory issues, as well as trouble digesting food.

Thankfully, there is a lot of awareness around CF in the medical field, and at birth, newborns are screened for the condition. This means that if they do have it, their treatment can begin right away, and they typically won’t have to seek out a diagnosis in later life. 

2. Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS) is a disease which affects the central nervous system. It typically begins with a weakness in the muscles which becomes more severe over time, affecting the patient’s ability to walk, talk, and even eat. There is still much to learn about this disease, but as far as researchers can tell, the disease seems to be hereditary.

It’s thought that around 5000 people in the UK suffer from ALS, meaning it affects roughly 1 in 13,500 people. The most well-known person to have had the condition is the highly-respected physicist Dr Stephen Hawking.

3. Congenital Insensitivity to Pain with Anhidrosis (CIPA)

Congenital Insensitivity to Pain with Anhidrosis (CIPA) is an extremely rare condition, with only around 300 cases that have been reported worldwide. Little is known about this condition, but patients exhibit a complete inability to feel pain or changes in temperature.

Although this may sound like a dream, CIPA can be very difficult to manage. Individuals with CIPA, particularly young children, must take particular care to regulate their temperature and ensure that they do not hurt themselves without realising. It can also be hard for them to detect when they are ill, as symptoms like upset stomachs, aches or pains will not register. 

4. Dissociative Identity Disorder (DID)

Dissociative Identity Disorder (DID), formerly known as Multiple Personality Disorder, is a condition which has been linked to trauma in early childhood. People with DID often experience periods of memory loss, but one of the most distinctive aspects of DID is that the person may exhibit more than one distinct personality. These personalities appear to ‘take over’ the person, and they may not remember what they were doing when this other personality has taken charge.

Because of inaccurate portrayals in films and other media, those who live with DID often face misunderstanding and discrimination. However, genuine cases of DID are rare, and the disorder has been estimated to affect as little  as 0.01% of the general population

5. Thyroid cancer

Although cancer itself is rather common, certain types of cancer fit the definition of a rare disease. Thyroid cancer, for instance, which receives only 2700 new diagnoses in the UK per year.

Thyroid cancer affects the thyroid gland — the small gland at the base of the neck which is responsible for hormone production. It can be treated in the same way that many cancers are treated. Depending upon the individual case, surgery, chemotherapy, and radiotherapy are all possible options.

What causes rare diseases?

With so many rare diseases and conditions, there is no single cause that unites them all. 

There are some, like Cystic Fibrosis, which are inherited. A person may not have any history of CF within their family, but their parents could both be carriers of a certain recessive gene. This means they won’t exhibit any symptoms themselves, but are capable of passing on the condition to their children. 

Missing genetic material can also be the cause behind some conditions. For instance, Prader-Willi Syndrome is caused by missing genetic material within the 15th chromosome. Chromosome abnormalities can be caused by prenatal contact with harmful substances, or more commonly, by an error which occurs during the dividing of cells. 

Though some rare diseases and conditions are genetic or inherited, there are some that are viral and can be passed from person to person. Or, as in the case of the Zika virus, a disease could also be caught from the bite of an infected mosquito.

Other conditions can be triggered by an injury or event. For instance, the link between Dissociative Identity Disorder and childhood trauma has been well-documented. On the other hand, the very rare condition, Foreign Accent Syndrome, has been linked to a number of physical causes like a brain injury or a stroke. 

Rare diseases: Final thoughts

At Simbec-Orion, we are passionate about helping to advance the treatment of rare diseases. If you’d like to discover more about studies into rare disease, you can browse a selection of clinical development case studies on our website.

We also have a dedicated whitepaper on this topic: Putting The Patient First: The Challenges and Opportunities to Improve Rare-Disease Therapy Development. If you’d like to discover more about the challenges faced by those researching rare diseases and what you can do to help, this whitepaper is free to download. If you would also like to get involved in Rare Disease Day, you can learn more about the events which take place worldwide on the official Rare Disease Day website. You can even list your own if you would like to take part and fundraise for those affected by rare diseases and conditions.

You can also learn more about how Simbec-Orion uses biomarker clinical trial design to drive rare respiratory disease results.

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