The 28th February 2019, marks the twelfth international Rare Disease Day. On and around this day hundreds of patient organisations from countries and regions across the globe will strive to raise awareness of some of the world’s rarest disease. For many of the rare diseases out there, we are yet to find cures, treatments and even causes. This is why Rare Disease Day is so important to the small patient populations suffering from a rare disease. Here are 5 of the world’s rarest diseases, their symptoms, causes, and treatments available — if any.



Pulmonary Arterial Hypertension PAH


Vascular abnormalities that are associated with pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a rare, progressive disorder characterized by high blood pressure (hypertension) in the arteries of the lungs (pulmonary artery) for no apparent reason.

Some patients with PAH do not seek medical advice until they are no longer able to continue with their normal activities. At this time, the disease may have progressed to a point where the patient is completely bedridden from shortness of breath or other symptoms. The exact cause of PAH is unknown.


Signs & Symptoms:

PAH symptoms are those that are usually due to not having enough oxygen in the blood and include:

  • Severe shortness of breath following exertion
  • Excessive fatigue
  • Weakness
  • Chest pain
  • Dizzy spells
  • Fainting episodes
  • Puffiness or swelling of the face, ankles, abdomen and feet due to abnormal accumulation of fluid (edema) within fascial tissues.

Individuals with advanced stages of PAH may have abnormal bluish discolouration of the skin due to low levels of circulating oxygen in the blood (cyanosis). In severe cases of PAH, the right chamber (ventricle) of the heart is abnormally enlarged (hypertrophy), resulting in diminished functioning of the right portion of the heart and, potentially, right heart failure.


Who is affected?:

PAH occurs 3-5 times more frequently in females as in males and tends to affect females between the ages of 30 and 60. New cases are estimated to occur in one to two individuals per million each year in the US and approximately 500-1000 new cases of PAH are diagnosed each year. The incidence is estimated to be similar in Europe.

There is no ethnic or racial group that is known to have a higher frequency of patients with PAH. An exception to this is an apparent paucity of cases of HPAH among people of African ancestry, although this may link to reporting bias and has not been rigorously studied.

A rare form of pulmonary hypertension affects individuals who are at high altitude levels (e.g., mountain climbers). It is not recommended for people with PAH or a family history of PAH to live at high altitudes.



Several medications have been approved by the US Food and Drug Administration (FDA) for the treatment of PAH. These medications can be broadly broken down into four categories: Prostaglandins, Endothelin Receptor Antagonists, Phosphodiesterase Type 5 Inhibitors and Supportive Therapies,



Guillain-Barre syndrome


Guillain-Barre syndrome nerve damage

Guillain-Barre (gee-YAH-buh-RAY) syndrome is a rare disorder which causes the body’s immune system attacks the nerves. Weakness and tingling in the hands and feet are usually the first symptoms.

These sensations can quickly spread, eventually paralyzing the whole body. In its most severe form, Guillain-Barre syndrome is a medical emergency. Most people with the condition must be hospitalized to receive treatment.

Once thought to be a single disorder, Guillain-Barre syndrome is now known to occur in several forms. The main types are:

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP), the most common form in the US. The most common sign of AIDP is muscle weakness that starts in the lower part of your body and spreads upward.

Miller Fisher syndrome (MFS), in which paralysis starts in the eyes. MFS is also associated with unsteady gait. MFS occurs in about 5 percent of people with Guillain-Barre syndrome in the US but is more common in Asia.

Acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN) are less common in the US But AMAN and AMSAN are more frequent in China, Japan and Mexico.

The exact cause of Guillain-Barre syndrome is unknown. But it is often preceded by an infectious illness such as a respiratory infection or the stomach flu.


Signs & Symptoms:

  • Prickling, pins and needles sensations in your fingers, toes, ankles or wrists
  • Weakness in your legs that spreads to your upper body
  • Unsteady walking or inability to walk or climb stairs
  • Difficulty with eye or facial movements, including speaking, chewing or swallowing
  • Severe pain that may feel achy or cramp-like and may be worse at night
  • Difficulty with bladder control or bowel function
  • Rapid heart rate
  • Low or high blood pressure
  • Difficulty breathing


Who is at Risk?:

Guillain-Barre syndrome can affect all age groups. But you’re at slightly greater risk if you’re a man or a young adult.

Guillain-Barre syndrome may be triggered by: infection with campylobacter, a type of bacteria often found in undercooked poultry (this is the most common trigger), Influenza virus, Cytomegalovirus, Epstein-Barr virus, zika virus, Hepatitis A, B, C and E, HIV, Mycoplasma pneumonia, Surgery, Hodgkin’s lymphoma, and in rare cases, influenza vaccinations or childhood vaccinations.



There’s no known cure for Guillain-Barre syndrome, but several treatments such as Plasma exchange (plasmapheresis) and Immunoglobulin therapy can ease symptoms and reduce the duration of the illness. Most people recover from Guillain-Barre syndrome, though some may experience lingering effects from it, such as weakness, numbness or fatigue.



Gaucher Disease


Magnified Gaucher disease Cells

Gaucher disease is an inherited (genetic) condition that is due to a deficiency in the enzyme glucocerebrosidase and leads to the accumulation of fatty substances in certain organs.

There are several types of Gaucher disease including type 1, 2, 3 Gaucher disease; perinatal lethal Gaucher disease, and cardiovascular Gaucher disease.

The most common type of Gaucher disease is type 1, and this type typically does not affect the nervous system. Type 2 and perinatal lethal Gaucher disease are rare and severe forms of the disease.



Signs and symptoms vary among people with Gaucher disease.

  • Enlarged liver and spleen
  • Fatigue
  • Anaemia
  • Bone pain and fractures
  • Easy bruising and bleeding.


Who is at risk?:

Gaucher disease is most common in people of Ashkenazi Jewish descent, affecting about 1 out of every 855 people. In the non-Jewish population, Gaucher disease affects 1 out of every 40,000 people.



Enzyme replacement therapy (ERT) is the main treatment for Gaucher disease.



Fabry Disease


Morbus Fabry ganglion cells

Fabry disease is an inherited disorder that results from the buildup of a particular type of fat, called globotriaosylceramide, in the body’s cells. Beginning in childhood, this buildup causes signs and symptoms that affect many parts of the body. Fabry disease also involves potentially life-threatening complications such as progressive kidney damage, heart attack, and stroke. Some affected individuals have milder forms of the disorder that appear later in life and affect only the heart or kidneys.

Fabry disease is caused by mutations in the GLA gene. This gene provides instructions for making the enzyme, alpha-galactosidase A. This enzyme is active in lysosomes, which are structures that serve as recycling centres within cells. Alpha-galactosidase A normally breaks down a fatty substance called globotriaosylceramide. Mutations in the GLA gene alter the structure and function of the enzyme, preventing it from breaking down this substance effectively. As a result, globotriaosylceramide builds up in cells throughout the body, particularly those lining blood vessels in the skin and cells in the kidneys, heart, and nervous system. The progressive accumulation of this substance damages cells, leading to the varied signs and symptoms of Fabry disease.


Signs & Symptoms:

  • Episodes of pain, particularly in the hands and feet
  • Clusters of small, dark red spots on the skin called angiokeratomas
  • Decreased ability to sweat (hypohidrosis)
  • Cloudiness of the front part of the eye (corneal opacity)
  • Problems with the gastrointestinal system
  • Ringing in the ears (tinnitus)
  • Hearing loss.


Who is at risk?:

Fabry disease affects an estimated 1 in 40,000 to 60,000 males. This disorder also occurs in females, although the prevalence is unknown. Milder, late-onset forms of the disorder are probably more common than the classic, severe form.

This genetic condition is inherited in an X-linked pattern — meaning the mutated gene that causes the disorder is located on the X chromosome. In males (who have only one X chromosome), one altered copy of the GLA gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or rarely may cause no symptoms at all.



There is currently no cure for Fabry disease. Treatment for Fabry disease includes enzyme replacement therapy along with medications to treat and prevent other symptoms of the disease. Kidney transplants may be needed in severe cases when renal failure occurs.



Von Hippel-Lindau


MR depicting retinal hemangioblastomas and an endolymphatic sac tumour.

Von Hippel-Lindau (VHL) disease is an inherited disorder characterized by the abnormal growth of both benign and cancerous tumours and cysts in many parts of the body. Tumours usually first appear in young adulthood. The types of tumours associated with VHL disease include hemangioblastomas (slow-growing tumours of the central nervous system); kidney cysts and clear cell renal cell carcinoma; pancreatic neuroendocrine tumours; pheochromocytomas (noncancerous tumours of the adrenal glands); and endolymphatic sac tumours. VHL disease is caused by a mutation in the VHL gene and is inherited in an autosomal dominant manner. Early detection and treatment of VHL disease is important, and usually involves surgical removal of tumours.


Symptoms & Signs:

Symptoms of von Hippel-Lindau (VHL) disease vary among patients and depend on the size and location of tumours.


  • Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination.
  • Hemangioblastomas can also occur in the retina which can cause blindness.
  • Pheochromocytomas affect the adrenal glands, which are small hormone-producing glands located on top of each kidney. These tumours often cause no symptoms, but in some cases, they can produce an excess of hormones that cause dangerously high blood pressure.
  • About 10% of people with VHL disease develop endolymphatic sac tumours —  non-cancerous tumours in the inner ear. These growths can cause hearing loss, tinnitus and problems with balance.
  • Individuals with VHL disease are also at a higher risk than normal for certain types of cancer, especially kidney cancer. Renal cell carcinoma occurs in about 70% of individuals with VHL disease by age 60 and is the leading cause of death.
  • Abnormality of the cerebral blood vessels
  • Abnormality of retina blood vessels
  • Absent/small cerebellum
  • Arteriovenous malformation
  • Neurological speech impairment


Who is at risk?

Mutations in the gene that causes VHL disease are inherited in an autosomal dominant manner, meaning that having a mutation in only one copy of the VHL gene in each cell is enough to increase a person’s risk of developing the disease.

However, in VHL disease, a mutation in the other copy of the gene must occur during a person’s lifetime to trigger the development of VHL disease. For example, a person may inherit a mutated copy of the gene from a parent, but acquiring a second mutation in the other gene copy in a specific organ may trigger tumour development in that organ. Almost everyone who is born with one VHL mutation will eventually acquire a mutation in the second copy of the gene and develop VHL disease.

In most cases, an affected person inherits the first mutated gene from an affected parent. However, in about 20% of cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.

When a person with a mutation that can lead to VHL disease has children, each of their children has a 50% (1 in 2) chance to inherit that mutation.



Treatment for Von Hippel-Lindau (VHL) disease depends on the location and size of tumours and usually involves surgical removal of tumours. Radiation therapy may be used in some cases.