Gaucher Disease

What Is Gaucher Disease?

Gaucher disease is a rare genetic (inherited) disorder that interferes with the way the body’s cells metabolize, or break down, a certain type of lipid called glucosylceramide. Glucosylceramide then builds up inside of the cells and causes harmful effects in many organs and tissues.

What Are the Types of Gaucher Disease?

Gaucher disease is broadly classified into three types that are based on how quickly the disease progresses and whether neurologic disease is present. Neurologic disease impacts the central nervous system which is comprised of the brain and spinal cord.

  • Gaucher disease type 1 mostly affects the liver, spleen and bone marrow. The central nervous system is unaffected. It is the most common and least severe form of the disease. Signs of disease may occur any time between childhood and adulthood. Well-managed patients with Gaucher disease type 1 can expect to live a normal lifespan.
  • Gaucher disease type 2 and type 3 are the neurologic forms of the disease.
    • Type 2 shows early signs of severe damage to the liver, spleen, bone marrow and the nervous system in early infancy. Type 2 disease worsens quickly. Severe brain damage occurs and children with Gaucher disease type 2 do not often survive beyond age 2.
    • Type 3 is a chronic (long-lasting) disease, and it follows a less predictable course than Gaucher type 2. Patients usually have a more gradual onset of symptoms, and they progress more slowly. The disease of patients with Gaucher type 3 can be managed, and patients may live well into middle age.

What Causes Gaucher Disease?

In healthy people, the lipid glucosylceramide (mentioned above) is broken down by an enzyme called glucocerebrosidase (GBA). The body’s instructions for making GBA are contained in the GBA gene. Everyone inherits two copies of the GBA gene, one from each parent. When both parents have one copy of a non-working GBA gene, they are carriers of Gaucher disease. Carriers do not have the disease, but when two carriers have a child, there is a 25% chance with each pregnancy that the child will have Gaucher disease. This pattern of inheritance is called autosomal recessive. The outcome of two non-working copies of the GBA gene is a lack of GBA enzyme. This causes a toxic build up of the lipid glucosylceramide inside cells of the body. These lipid-laden cells are sometimes called Gaucher cells.

What Are the Symptoms of Gaucher Disease?

Symptoms for Gaucher disease type 1 vary widely from patient to patient, and they may occur any time between childhood and adulthood. The most common symptoms may include:

  • Tiredness due to anemia (a low red blood cell count)
  • Easy bleeding or bruising due to a low platelet count
  • A swollen abdomen due to an enlarged spleen and/or liver
  • Bone pain due to reduced blood flow to the bone

In addition to the symptoms listed above for Gaucher disease type 1, patients with types 2 and 3 often have:

  • Abnormal eye movements
  • Seizures (epilepsy)
  • Developmental delay (a child being less developed mentally or physically than children of the same age)
  • Breathing problems
  • Difficulty swallowing
  • Uncontrollable tightening and releasing of muscles

How Is Gaucher Disease Diagnosed?

A diagnosis of Gaucher disease should include these two important tests: GBA enzyme activity of white blood cells, followed by a molecular analysis to look for genetic changes in the GBA gene. In patients with Gaucher disease, enzyme activity is typically very low, only 0-15% of normal. The level of enzyme activity does not reliably show the difference between disease types or relate to the severity of the disease. Newborn screening for Gaucher disease is currently being started in select states including Illinois. The sooner a child is identified with Gaucher, the sooner the symptoms and course of the disease can be managed. In addition, testing of parents, siblings and other family members may be done.

How Is Gaucher Disease Treated?

Currently, enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) are available treatments for Gaucher disease. ERT involves an infusion of a commercial form of the GBA enzyme that is given intravenously (through the vein). The infusions must be done on a regular basis, most often twice per month. The infused enzyme helps to breakdown the lipid that is building up in the body’s cells. Three FDA-approved ERTs are currently prescribed in the US: imiglucerase (Cerezyme®), velaglucerase alfa (VPRIV®) and taliglucerase alfa (Elelyso®). SRT works to slow or interfere with the body’s own production of glucosylceramide, thus reducing or stopping the build-up of this lipid. SRT is taken orally (by mouth). Dosing of SRT must be carefully managed by the patient’s healthcare team. Two SRTs for Gaucher disease type 1 have been approved by the FDA for adults only, eliglustat (Cerdelga®) and miglustat (Zavesca®).

Additional Resources

National Gaucher Foundation

The International Collaborative Gaucher Group (ICGG) Gaucher Registry

ClinicalTrials.gov

The National Organization for Rare Disorders