Gaucher Disease
What Is It?
Gaucher Disease (GD) is an inherited condition that can damage many different parts of the body. Damage occurs when a type of fat — glucocerebroside — builds up in certain organs in the body. Normally, we have an enzyme—glucocerebrosidase — that eliminates this bad fat. People with GD do not make enough of this enzyme. GD typically causes a large liver and spleen, anemia, low platelet count, lung disease, and sometimes brain disease.
There are three basic types of GD. Type 1 causes nearly all of the symptoms listed above, except for brain disease. Types 2 and 3 cause all the listed symptoms, including effects on the brain. Type 2 is the most severe, with symptoms beginning before age 2. In Type 3 GD, the symptoms may begin before age 2, but are more mild and slower to worsen. More recently, experts on Gaucher disease have realized that some patients do not exactly fit into these categories. Symptoms of patients with Type 2 and Type 3 can vary.
GD is rare; it affects about 1 person in 100,000. In certain ethnic groups, such as Ashkenazi Jews, type 1 GD can affect up to 1 in 1,000 people. About 90% of people with GD have type 1, making it the most common form.
All three types of GD are caused by a change, or mutation, in a gene called GBA, which is responsible for making the glucocerebrosidase enzyme. Gaucher disease is an autosomal recessive genetic disorder. This means that the person with the disease must inherit two mutations in the gene, one from their mother and one from their father. Without any normal GBA gene, the person cannot make sufficient amounts of glucocerebrosidase to prevent the abnormal fatty accumulation.
If both parents carry a genetic mutation for GD, each of their children has a 25% chance of inheriting GD. Usually the parents do not know that they carry the gene. Some ethnic groups — such as Ashkenazi Jews — often get tested to determine if they are carriers before having children.
Symptoms
Newborn babies with GD do not show any symptoms. Depending on the type of GD, symptoms develop at different times. In type 1 GD, symptoms may not become apparent until a person is a young adult; but some patients get liver and spleen enlargement in childhood (sometimes as young as age 1 or 2). In most people, type 1 causes a large liver and spleen, anemia, low platelets, and thinning and weakening of bones. Anemia can cause fatigue, while low platelets can lead to easy bruising and nosebleeds.
Type 2 and Type 3 GD cause neurological symptoms. In the past, these names were used to separate patients into categories of more severe (type 2) and less severe (type 3). Typically, Type 2 has meant that symptoms start as early as 3 months old. In addition to the typical GD symptoms, people with type 2 GD often have neurological problems such as severe developmental delays, muscle stiffness, and possibly seizures.
Type 3 GD has typically meant that symptoms usually start in childhood or adolescence. It can cause enlarged liver and spleen, but these symptoms don't show up consistently in all patients. It also causes neurological problems such as confusion or dementia, worsening mental function, abnormal eye movements, and muscle weakness. The symptoms do not get worse as quickly as they do in people with type 2. Types 2 and 3 are similar because they both involve neurological symptoms, while Type 1 does not.
Cardiovascular GD is another type that mainly affects the heart. These patients may also get an enlarged spleen, cloudy corneas, and abnormal eye movements.
Diagnosis
Symptoms can be different from one person to another, so GD cannot be diagnosed without laboratory testing. Blood tests can reveal anemia and other low blood counts. Doctors may perform a bone marrow biopsy to determine the cause of low blood counts. If the bone marrow biopsy suggests GD, then your blood will be tested again to prove that the glucocerebrosidase enzyme is not working properly. Genetic testing of the GBA gene is possible, but should not take the place of enzyme testing.
Expected Duration
GD is an inherited disorder that lasts throughout a person's lifetime.
Prevention
GD occurs when a baby inherits two copies of the mutated gene that causes GD, one from each parent. Each parent usually has only one copy of the mutated gene and therefore doesn't have GD. Because the parents don't know they are carrying the mutated gene, there is nothing they can do to prevent their babies from having the disorder.
Caring for someone with GD involves trying to prevent complications from the disorder.
Treatment
GD is caused by low levels of the glucocerebrosidase enzyme, so the best treatment is enzyme replacement therapy (ERT) with a synthetic enzyme called imiglucerase (Cerezyme). The synthetic enzyme is given as an intravenous (IV) drug. Regular IV infusions of imiglucerase have been demonstrated to be safe and effective in reversing low blood cell counts, and enlargement of the liver and spleen.
Approximately 10% to 15% of people develop antibodies to the replacement enzyme, although in most cases these people remain symptom-free. A newer treatment, Miglustat, is available for people who stop responding to ERT. Miglustat is taken by mouth, and helps decrease the enlarged liver and spleen, strengthen the bones, and may improve other symptoms as well.
People with type 1 GD and type 3 GD live longer than people with type 2 GD. Over time, people with type 1 and type 3 may become resistant to the effect of medications. In those cases, bone marrow transplantation may be recommended.
Other treatments may help relieve the symptoms of GD, but they won't combat the cause. For example, surgery to remove the spleen helps some patients because an enlarged spleen can destroy platelets as they pass through the spleen. Blood transfusions can treat severe anemia. Bone pain can be treated with pain medication. Sometimes, joint replacement surgery is needed. Medications that help increase bone density can also be helpful in some people. Of the medications that increase bone density, the most commonly used ones are the bisphosphonates, such as alendronate (Fosamax), ibandronate (Boniva) and risedronate (Actonel).
When To Call a Professional
Symptoms of GD may develop gradually. If you or your child has the symptoms described above, make an appointment with your primary care provider. You may also need to see a blood specialist, or hematologist, and possibly a neurologist or geneticist.
Prognosis
The prognosis is different for each type of GD. Type 2 GD typically results in severe developmental delay and death by age 2 to 4; even with treatment, life expectancy for people with type 2 GD is shortened. Children with type 3 GD may live into their twenties or thirties. Some people with very mild type 1 GD may have so few symptoms that they are never diagnosed, and have a normal life expectancy.
Additional Info
National Gaucher Foundation
2227 Idlewood Road, Suite 12
Tucker, GA 30084
800-504-3189
www.gaucherdisease.org/
Disclaimer: This content should not be considered complete and should not be used in place of a call or visit to a health professional. Use of this content is subject to specific Terms of Use & Medical Disclaimers.
