Gaucher disease
- Reviewed by Howard E. LeWine, MD, Chief Medical Editor, Harvard Health Publishing; Editorial Advisory Board Member, Harvard Health Publishing
What is Gaucher disease?
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 (GD1) causes nearly all of the symptoms listed above, except for brain disease. GD2 and GD3 cause all the listed symptoms, including effects on the brain. GD2 is the most severe, with symptoms beginning before age 2. In GD3, the symptoms may begin before age 2, but are more mild and slower to worsen. Some patients do not exactly fit into these categories. Symptoms of patients with GD2 and GD3 can vary.
GD is rare; it affects about one person in 50,000 to 100,000. In certain ethnic groups, such as Ashkenazi Jews, GD1 can about one in 850 people. About 90% of cases are GD1, 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 of Gaucher disease
Newborn babies with GD do not show any symptoms. Depending on the type of GD, symptoms develop at different times. In GD1, symptoms may not become apparent until a person is a young adult, but some patients develop liver and spleen enlargement in childhood (sometimes as young as age 1 or 2). In most people, GD1 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.
GD2 and GD3 cause neurological symptoms. In the past, these names were used to separate patients into categories of more severe (GD2) and less severe (GD3). Typically, GD2 has meant that symptoms start as early as 3 months old. In addition to the typical GD symptoms, people with GD2 often have neurological problems such as severe developmental delays, muscle stiffness, and possibly seizures.
GD3 typically starts causing symptoms 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 GD2. GD2 and GD3 are similar because they both involve neurological symptoms, while GD1 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.
Diagnosing Gaucher disease
Symptoms can be different from one person to another, so GD cannot be diagnosed without laboratory testing. The diagnosis may be suspected when routine blood tests are abnormal, such as a low red blood cell count causing anemia. The standard diagnostic test for GD is measurement of glucocerebrosidase enzyme activity in white blood cells. Doctors may also perform a bone marrow biopsy if there is any concern for another cause of low blood cell counts.
Expected duration of Gaucher disease
GD is an inherited disorder that lasts throughout a person's lifetime.
Preventing Gaucher disease
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.
Treating Gaucher disease
GD is caused by low levels of the glucocerebrosidase enzyme. There are two types of treatment available for GD1. The first is called enzyme replacement therapy (ERT) which involves providing a synthetic enzyme to take the place of the natural enzyme that does not work well in an affected person. ERTs are available for moderate to severe GD1. The synthetic enzyme is given as an intravenous (IV) drug. Regular IV infusions ERT have been demonstrated to be safe and effective in reversing low blood cell counts, in decreasing the size of the liver and spleen, and can improve quality of life within the first year of treatment.
Another type of treatment for GD1 is called substrate reduction therapy (SRT), and involves reducing the amount of work for the remaining enzyme. SRT is approved for people with mild to moderate GD1. SRT is taken by mouth and helps decrease the enlarged liver and spleen, strengthen the bones, and may improve other symptoms as well.
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. With modern treatment, the prognosis of people with GD1 is excellent. GD2 typically results in severe developmental delay and death by age 2 to 4; even with treatment, life expectancy for people with GD2 is shortened. Children with GD3 may live well into adulthood, although they may have significant health issues related to the disease.
Additional info
National Gaucher Foundation
www.gaucherdisease.org/
About the Reviewer
Howard E. LeWine, MD, Chief Medical Editor, Harvard Health Publishing; Editorial Advisory Board Member, Harvard Health Publishing
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