Rare diseases

The global impact of rare diseases cannot be ignored

Collectively rare diseases affect around
350 million people worldwide – enough people for the third most populous country in the world.

Thirty percent of children born with
a rare condition die before
their fifth birthday.

Rare diseases are fundamental to modern medicine. Around 80% have a genetic basis – understanding them will help us understand human biology.

What are rare diseases?

The EU defines rare diseases as conditions that affect less than 1 in 2,000 people, but many are much rarer. While Duchenne muscular dystrophy affects 2,500 people in the UK, Wolfram syndrome affects a mere 100. Many syndromes without a name (known as SWAN) are only known in a single person.

Over 7,500 rare diseases have been identified, 80% of which are genetic. They can affect people at different times in their lives, affect a single system of the body, or display symptoms across multiple organs. Due to this, rare diseases are rarely considered as a group by the medical profession, meaning there are no rare disease specialists. Instead, each condition falls under the care of one or more different specialities.

The following examples highlight the diversity of rare conditions and their impact on patients. You can find a list of all the 7,000+ rare diseases on the Orphanet website.

Fibrodysplasia ossificans progressiva

Prevalence: roughly 1 in 2,000,000

Summary: Some rare diseases are highly visible and shocking. Fibrodysplasia ossificans progressiva, otherwise known as stone man syndrome or FOP, is one such example. This condition causes fibrous tissue to be ossified (turned to bone) spontaneously or due to trauma . A patient’s body slowly turns to bone over the course of their life, causing severe limitations in movement and is ultimately fatal, greatly reducing life expectancy to a median age of 40. FOP is the only known medical condition where one organ system changes into another.

Treatment: None currently, but there is significant academic research effort into the condition.

Links: fopfriends.com/fop-friends

Ehlers Danlos syndrome

Prevalence: Unknown

Summary: The symptoms of many rare conditions are relatively hidden. Ehlers-Danlos syndrome is a collection of thirteen individual rare genetic conditions that affect the connective tissues. These conditions often lead to stretchy skin and over-extension of the joints. Patients also live with long-term pain, chronic fatigue, and digestive disorders. EDS affects people to differing extents; for some it is mild whilst for others it is debilitating.

Treatment: None

Links: www.ehlers-danlos.org.uk

Tyrosinemia type 1

Prevalence: Unknown

Summary: Rare diseases can have extremely poor outlook from birth. Tyrosinemia type 1 is caused by a faulty enzyme that prevents the breakdown of tyrosine. In the acute form of the condition, patients experience liver failure within the first months of life. Patients are unlikely to survive long without treatment.

Treatment: Nitisinone and a low-protein diet allow patients to live in good health.

Duchenne muscular dystrophy

Prevalence: Roughly 2,500 patients in the UK, 300,000 worldwide.

Summary: Many rare conditions are degenerative, with symptoms developing and worsening throughout life. Duchenne Muscular dystrophy is the most common fatal genetic disease in childhood. The condition predominantly affects boys, who experience a progressive loss of muscle strength and function as they grow. Most are wheel chair bound by the age of 12. It is unusual for Duchenne patients to live beyond their 30s.

Treatment: None, but there and multiple different treatment approaches currently in clinical trials.

Links: www.duchenneuk.org

Cystic fibrosis

Prevalence: Between 1 in 8,000 and 1 in 10,000

Summary: Cystic fibrosis is the most common genetic condition among caucasian children, and a rare disease that many people have heard of. The condition affects the body’s secretions, mainly sweat and mucus, and can lead to severe respiratory and digestive problems. Treatments only target symptoms, but have taken life expectancy from around the age of 5 in the 1960’s to 40 years today.

Treatment: Symptomatic treatments only.

Links: www.cysticfibrosis.org.uk

NGLY-1 deficiency

Prevalence: 63 patients are known worldwide

Summary: The NGLY-1 mutation was identified in 2012, in a young boy named Bertrand Might. He was then the only known person with this rare mutation. A social media campaign by his family identified other patients, and they have now formed a growing patient community spearheading research and improved care. Patients experience a complex mixture of physical and neurological symptoms, including lack of sweat and tears, seizures, difficulty with walking and talking, and sleep apnoea.

Treatment: None

Links: www.ngly1.org

Sources: Rare disease statistics based on data collected by Rare Disease UK. Information on specific rare diseases is based on information provided by Orphanet.

The symptoms caused by different rare diseases are hugely diverse, yet all patients share common experiences that unite them. As rare diseases are so uncommon, they tend to be overlooked by doctors, researchers, and the general public. This means that individuals do not get the support that they need. After facing a journey of repeated misdiagnoses, many will find that there is no treatment available, no research into their condition, and no national support group or charity. They simply have to go home and deal with it, where their local GP may never have even heard the name of their condition.

While their health deteriorates, many patients struggle to keep their jobs, or in the case of children, many have to drop out of education and are life-limited. This isolation and sense of abandonment has ultimately led patients, families and carers to take control of their own conditions. Rare diseases are at the forefront of patients managing their own care, of forming patient organisations for mutual support, of funding research, and of patient engagement in research.

Together we are strong

The shared experiences across all conditions mean that patients with very different medical challenges are coming together under a unified voice. They learn from one another, support one another, and have a stronger presence to help secure the attention and treatments that all rare diseases need.

BM Manifesto is working to build a rare disease community that supports, informs, and collaborates together for the betterment of all rare conditions. We work directly with patient groups to break their isolation and ensure that their knowledge and experience is valued by the medical community.

The challenges of rare science

A lack of research, knowledge, and treatments causes many of the obstacles facing individuals living with a rare condition. So why is rare science so hard?

1. Patients are rare – to research a condition you need to find patients. These are few and far between for any rare condition, and until a disease is well understood, securing an accurate diagnosis is also exceptionally challenging.

2. Knowledge is limited – with little pre-existing knowledge and few disease models it is hard to identify potential treatments.

3. Multiple symptoms treated by different specialists – doctors often specialise in a certain body system, but many rare diseases affect multiple systems. When different symptoms are treated by different doctors no one has the full picture and key connections will be missed.

4. Funding – funding is harder to secure if the condition is not a research priority for governments, industry, funding bodies, or charities.

5. Market – developing a treatment for a rare disease can be less expensive than for a more common illness, but the costs are still high. With a limited number of patients to treat the pharmaceutical industry can view the development of rare disease drugs as financially non-viable.

Rare is fundamental

Research and support for rare diseases are crucial because it helps us to fundamentally change the way we deliver care and treatment to the patients of the future.

  • Rare diseases are at the forefront of patient engagement in medical research and drug development. They are fundamentally changing the way that new treatments are delivered, creating a focus on patient need and patient experience.
  • Rare diseases are some of the conditions targeted by the first pioneering gene therapies to reach patients. They form the testbed upon which new curative genetic medicines are developed.
  • Rare diseases serve as model systems for more common conditions. They are often biological edge cases, that help us better understand human biology.

Fundamental diseases

There are many instances where improved scientific knowledge of a rare disease has acted as a gateway to understanding, or even treating, much more common conditions. We call such rare conditions fundamental diseases.

Recognising the connections between rare and common conditions is crucial for both scientific advancement and the promotion of rare disease research. If diseases share similar underlying mechanisms, they are likely to benefit from similar treatments. For pharmaceutical companies, rare diseases linked to common conditions can often act as a gateway into a larger market, and this can bring much-needed investment into rare disease research.

Case study: Familial Hypercholesterolemia (FH)

FH is a rare genetic illness that leads to a build-up of bad cholesterol in the blood. This clogs blood vessels, and increases the risk of a heart attack.

In FH patients the system that monitors and breaks down the bad cholesterol is damaged, meaning that less is removed from the blood. Normally, the breakdown of cholesterol also tells the body to slow its natural cholesterol production. As FH patients don’t break down the bad cholesterol, cholesterol keeps being produced and keeps building up.

By studying FH, scientists gained a better understanding of how cholesterol is managed in the body. This led to the discovery of statins – drugs that slow the body’s natural cholesterol production and increase the removal of bad cholesterol from the blood. While this can help FH patients, it has also helped millions of people who have high cholesterol and are at risk of heart disease.

Fibrodysplasia Ossificans Progressiva (FOP)

A rare disease, known as Stone Man Syndrome, where the body slowly turns muscle to bone. It has boosted knowledge of the disease heterotopic ossification, when bone forms in the soft tissues and is common following joint replacement opperations.


A rare genetic disease also called Black Bone Disease. It is a model for osteoarthritis, a disease affecting millions of people.

Congenital Leptin Deficiency

This ultra-rare genetic disease is characterised by severe early-onset obesity and marked over-eating. The study of this disease is leading to the discovery of new obesity genes.

Congenital Generalised Lipodystrophy (CGL)

This rare genetic disorder is characterised by near complete absence of body fat, high levels of fats in the bloodstream and insulin resistance. Studying this extreme form of insulin resistance is helping to understand type 2 diabetes.