Spotlight on Gaucher Disease: What Causes It, and Is There a Cure?

Gaucher disease (pronounced “go-SHAY”) is a rare genetic disorder that affects an estimated 1 in 40,000 live births in the United States. In this article, we take a look at the disease’s cause and symptoms, as well as its treatment and the prognosis for those born with the disorder.

What is Gaucher disease?

Gaucher disease results from a lack of glucocerebrosidase (GCase), a vital enzyme responsible for breaking down glucocerebroside, a fatty chemical that, if left unchecked, causes the accumulation of Gaucher cells in the bone marrow, liver and spleen. A recessive gene mutation causes Gaucher disease.

Recessive genetic disorders require two copies of the associated gene mutation to present symptoms. Both parents must therefore be carriers of the same mutation and pass it on to their children.

When two Gaucher disease-carriers have a child together, the odds of them passing down the disorder to that child are 1 in 4. The odds that their child will be a carrier are 1 in 2. The odds that their child will neither be a carrier, nor have the disorder, are 1 in 4. Because of these odds, genetic disorders can pass down through the generations silently, occurring unexpectedly in families with no apparent history of the disease. The only way to accurately determine whether you carry the gene mutation associated with Gaucher disease is through genetic carrier screening.

Gaucher disease is most prevalent in people of Ashkenazi Jewish descent, with approximately 1 in 450 people in this community affected by the disorder and 1 in 10 estimated to be carriers. Nevertheless, the disease can occur in people of all ethnicities. The American College of Obstetrician and Gynecologists advises that all women planning to have children should undergo genetic carrier screening, irrespective of their family history or ethnic origin.

What are the symptoms of Gaucher disease?

The disease causes fatty substances to accumulate in the vital organs, particularly the liver and spleen. This can affect organ function and cause them to become enlarged. Gaucher cells can also build up in bone tissue, affecting bone strength and increasing the likelihood of fractures. Similarly, the disease can affect the bone marrow, inhibiting blood clotting.

Common symptoms include:

· Abdominal pain: The enlargement of the liver and spleen can cause painful distention of the abdomen.

· Blood disorders: When the disease affects bone marrow, this can interfere with the body’s production of cells needed for blood coagulation, resulting in excessive and unexplained bleeding and bruising. Gaucher disease can also cause a decline in the production of heathy red blood cells, resulting in anemia.

· Skeletal abnormalities: Bone density can decline, increasing susceptibility to fractures. Gaucher disease can also inhibit blood supply to bones, interrupting the delivery of vital oxygen and causing portions of bone to die.

In rarer cases, the disease can affect the brain and neurological system, causing difficulties in swallowing, muscle rigidity, and abnormal eye movements.

How is Gaucher disease diagnosed?

People with the above symptoms of Gaucher disease can undergo testing to measure GCase levels in the blood. Secondary testing can involve analysis of the individual’s DNA to check for the four most common genetic markers associated with the disorder.

How is Gaucher disease treated?

Though there is currently no known cure for Gaucher disease, specialists have developed treatments to manage the disorder’s symptoms. A relatively new innovation is enzyme replacement therapy, which involves administering a modified form of GCase to the patient via an intravenous infusion on a biweekly basis, effectively halting progression of the disorder and often reversing symptoms. This has been used with some success, though when the brain and nervous system have been compromised, no improvement has been reported.

Other therapies used to treat Gaucher disease include pain relief medications and blood transfusions, as well as surgical interventions such as joint replacements and removal of the spleen.

What is the prognosis for people who have the disorder?

The disease varies greatly from person to person in terms of the severity of symptoms, even when it is found in identical twins.

There are three main subtypes of the disease, with Type 1 being the most common and often the mildest form. Type 2 is generally the most severe, usually starting in infancy and leading to rapid neurological decline and death. People with Type 3 Gaucher disease experience symptoms ranging in severity between those associated with Type 1 and Type 2, but with some neurological problems. These patients can experience spleen, liver, and brain problems, and though they often live well into adulthood, their lifespan may be cut short.

How could gene therapy lead to a cure for Gaucher disease?

In recent studies, scientists have successfully halted the progression of symptoms in mice through the implementation of gene therapy. Dr. Simon Waddington and Dr. Ahad Rahim made the breakthrough while working with a team of specialists from University College, London. The Gauchers Association in the United Kingdom cited the achievement as taking the world a step closer to potentially finding a cure for this rare genetic disorder.