Symptoms

Signs and symptoms of Gaucher's disease can vary widely depending on the type of the disease and the person affected. Siblings, even identical twins, with the disease may have different levels of severity.

The major types of Gaucher's disease and associated symptoms are:

Type 1
This form of the disease is the most common and generally the mildest. Type 1 accounts for about 90 percent of cases. In this form of the disease, there's usually no damage to the brain. This type can occur at any age, although it's most common in adults, with an average age of 30 at the time of diagnosis. Possible signs and symptoms of type 1 Gaucher's disease include:

• Skeletal abnormalities, including thinning of your bones (osteopenia), bone pain and bone fractures
• Enlarged liver (hepatomegaly) or spleen (splenomegaly), or both
• A decrease in healthy red blood cells (anemia)
• Excessive fatigue
• A greater susceptibility to bruising, which may mean you have a low number of blood platelets (thrombocytopenia)
• Yellow spots in your eyes (pingueculae)
• Delayed puberty
• Nosebleeds

Type 2
This form of Gaucher's disease is rare and more severe than the other types. It begins during the first year of life, often developing by 3 months. Babies with type 2 Gaucher's disease have extensive brain damage that progresses rapidly. In addition to the signs and symptoms listed for type 1, other possible problems that may occur with type 2 include:

• Brain problems, including mental retardation or dementia
• Rigidity
• Seizures

Type 3
This form of Gaucher's disease, also rare, usually begins in childhood or adolescence. It tends to be chronic and progresses more slowly than does type 2. Although the brain is affected, brain involvement tends to be milder than in type 2. Signs and symptoms, such as enlargement of the liver and spleen, tend to vary more in intensity than in type 2. Signs and symptoms that may occur more in type 3 than in type 1 include:

• Brain problems, including mental retardation or dementia
• Abnormal eye movements
• Loss of muscle coordination

When to see a doctor
If you or your child has any of the signs and symptoms associated with Gaucher's disease, make an appointment with your doctor.

Causes

The cause of Gaucher's disease is a deficit of the enzyme glucocerebrosidase. This enzyme normally breaks down fatty substances (lipids) called glucocerebrosides. When the enzyme is scarce, however, the fatty substances can build up in your brain and other organs, and within your bone marrow.

Gaucher's disease is passed along in an inheritance pattern called autosomal recessive. Both parents must be carriers of a Gaucher's genetic mutation for their child to develop the condition. So far, researchers have noted more than 300 genetic mutations associated with Gaucher's disease. Even when both parents are carriers, there's still only a 25 percent chance that their child will develop the disease, compared with a 50 percent chance of their child being an unaffected carrier, and a 25 percent chance of his or her not being a carrier and not having the disease.

Risk factors

The risk of having type 1 Gaucher's disease or being a carrier is higher if you're of Eastern or Central European Jewish (Ashkenazi) ancestry. Types 2 and 3 can occur in any ethnic group, except for a certain form of type 3 that's more common in people of Swedish descent.

A family history of any type of Gaucher's disease increases the risk of being either a carrier of Gaucher's or of developing the disease.

Complications

All types of Gaucher's disease tend to be progressive. Possible complications depend on the type of Gaucher's disease.

Complications of all types
Possible complications of all types of Gaucher's disease include:

• Bone pain, which can become severe and may be associated with fractures.
• A tendency to bleed, which may result in repeated hemorrhaging in the nostrils or nasal cavities, or bruising in the skin (ecchymosis).
• An increased risk of certain cancers. Older people with Gaucher's disease may have an increased likelihood of developing certain types of cancer, particularly multiple myeloma — uncontrolled multiplication of plasma cells.

Complications of type 2
Complications that are more likely to occur in people with type 2 Gaucher's disease often include serious neurological complications, such as:

• Seizures
• Difficulty walking
• Swallowing problems

As these problems progress and become more severe, they can become debilitating and lead to death.

Complications of type 3
People with type 3 Gaucher's disease are more likely to develop calcification of heart valves, which damages the valves and makes it increasingly difficult for them to open fully and function properly.

Preparing for your appointment

You're likely to start by seeing your family doctor, a general practitioner or a pediatrician, depending on your age. However, you may then be referred to a doctor who specializes in blood disorders (hematologist). Depending on the type of complications you experience, you may also need to consult other doctors, such as a doctor who specializes in brain and nervous system disorders (neurologist).

Here's some information to help you get ready for your appointment, and to know what to expect from your doctor.

What you can do

• Write down any symptoms you're experiencing or your child is experiencing, including any that may seem unrelated to the reason for which you scheduled the appointment.
• Write down key personal information, including any major stresses or recent life changes.
• Make a list of all medications, vitamins and supplements you're taking or your child takes.
• Try to create a family medical history. Of particular importance is whether anyone in the family has been diagnosed with Gaucher's disease, as well as whether anyone died in infancy.
• Ask a family member or friend to join you, if possible. Someone who accompanies you can help you remember the information your doctor gives you.
• Write down questions to ask your doctor.

Preparing a list of questions may help you make the most of your time with your doctor. For Gaucher's disease, some basic questions to ask your doctor include:

• What's the most likely cause of these symptoms?
• Are there other possible causes for these symptoms?
• What kinds of tests are needed? Do these tests require any special preparation?
• What's the prognosis?
• What treatments are available, and which do you recommend?
• What types of side effects can be expected from treatment?
• Are there any alternatives to the primary approach that you're suggesting?
• I have other health conditions. How can I best manage them together?
• Are there any restrictions?
• Can I have children? Will I pass this disease on to them?
• Are there any brochures or other printed material that I can take home with me? What websites do you recommend?

Don't hesitate to ask any other questions that occur to you.

What to expect from your doctor
Your doctor is likely to ask you a number of questions. Being ready to answer them may reserve time to go over any points you want to spend more time on. Your doctor may ask:

• When did symptoms begin?
• How severe are the symptoms?
• Does anything seem to improve or worsen your symptoms?
• Do you know if anyone in your family has had Gaucher's disease? If yes, do you know what type?
• What's your family's heritage?

Tests and diagnosis

Making the diagnosis
If your doctor suspects Gaucher's disease or if Gaucher's disease runs in your family, the diagnosis is made by checking levels of the enzyme associated with the disease, and possibly through genetic analysis:

• Enzyme analysis. Using a blood test, doctors can measure your levels of glucocerebrosidase. People with Gaucher's disease have low levels of this enzyme in their bloodstream. If you're a carrier of the gene responsible for Gaucher's — but don't have the disease itself — you'll have an intermediate enzyme level that falls between those of affected people and those who aren't carriers.
• Genetic mutation analysis. This test looks for the four most common, as well as some less common, genetic mutations known to be associated with Gaucher's disease. However, because it's unlikely that all of the genetic mutations involved in Gaucher's have been identified, this test isn't considered definitive. It can be used to help classify which type of Gaucher's you or your child has.

Tracking the progression
If you receive a diagnosis of Gaucher's disease, your doctor may recommend periodic tests to track its progression. These may include imaging tests such as:

• Dual energy X-ray absorptiometry (DXA), which uses low-level X-rays to measure bone density, including changes over time
• Magnetic resonance imaging (MRI), which use a magnetic field and radio waves to create images, to help your doctor see whether you have an enlarged spleen or liver

Preconception screening and prenatal testing
If you're planning to become pregnant and you or your partner is of Ashkenazi Jewish heritage or has a family history of Gaucher's disease, talk to your doctor about genetic screening. If only one of you is Ashkenazi, that person should be screened first. If that person is found to be a carrier, the other partner may want to be screened, as well. If you're identified as a carrier, ask your doctor about genetic counseling.

For pregnant women who are carriers of the Gaucher's gene, doctors may recommend prenatal testing for genetic mutations that can determine whether the fetus is at risk of Gaucher's disease. Tests that evaluate cells in the amniotic fluid (amniocentesis) or evaluate tissue from the placenta (chorionic villus sampling) can detect all types of Gaucher's in the fetus. If you're considering one of these tests, ask your doctor for a referral to a genetic counselor who can help you look at the risks and benefits.

Treatment and drugs

Some people with type 1 disease have such mild symptoms that they may not need treatment. There's no specific treatment for type 2 Gaucher's disease.

To treat type 1 or 3 Gaucher's disease, your doctor may recommend:

• Enzyme replacement therapy. This approach replaces the deficient enzyme with artificial enzymes. These replacement enzymes are administered in an outpatient procedure through a vein (intravenously), typically in high doses at two-week intervals. Although results can vary, treatment is frequently effective in people with type 1 Gaucher's disease and, in some cases, type 3. In many people, enzyme replacement therapy can reduce the enlargement of the liver and spleen, help to resolve blood abnormalities and improve bone density. It's unclear whether this therapy is effective for the neurological problems of Gaucher's disease. Occasionally people experience an allergic or hypersensitivity reaction to enzyme treatment.
• Bone marrow transplantation. This surgical procedure has been used for severe cases of Gaucher's disease. In this technique, blood-forming cells that have been damaged by Gaucher's are removed and replaced, which can reverse many of Gaucher's signs and symptoms. Because this is a high-risk approach, it's performed less often than is enzyme replacement therapy.
• Medication. The oral medication miglustat (Zavesca) has been approved for use in people with Gaucher's disease. It appears to interfere with the production of glucocerebrosides in some people with type 1 disease. Diarrhea and weight loss are common side effects. This medication may also affect sperm production. Contraception is advised while using miglustat and for three months after stopping the drug.

Pregnancy
Although pregnancy may worsen the symptoms of Gaucher's disease, most women who have the disease can have a successful pregnancy. However, it's not clear if enzyme replacement should be continued during pregnancy.

Prognosis
People with mild cases of Gaucher's disease, particularly those who develop it in adulthood, have close to normal life expectancies. Children whose illness begins during infancy generally don't live beyond 2 years old. However, children with type 3 who live into their teens often survive for many more years.

Coping and support

Having any chronic illness can be difficult, but having a rare disease like Gaucher's may be even harder. Few people know about the disease, and even fewer understand the challenges you face. You may find that talking to someone else who has the disease or has a child with Gaucher's is helpful.

The National Gaucher Foundation has a mentor program that connects people who have the disease. To find out more you can visit its website or call 800-504-3189. Additionally, your doctor may know if there are any local support groups in your area.