Gaucher's (go-SHAYZ) disease occurs when certain harmful fatty substances build to excessive levels in your liver, spleen, lungs, bone marrow and, less commonly, your brain. This accumulation of fatty material in tissues interferes with the normal functioning of the body's organs, and may cause organ enlargement and bone pain.

Gaucher's disease is caused by a deficiency of the enzyme glucocerebrosidase, which helps the body metabolize the fatty substance glucocerebroside. The disease is sometimes called glucocerebrosidase deficiency.

Gaucher's disease can occur at any age. It's most common in Eastern and Central European (Ashkenazi) Jewish people.

Treatment for Gaucher's disease may involve enzyme replacement and other therapies.

Signs and symptoms of Gaucher's disease can vary widely from one person to another, particularly among different types of the disease.

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

Type 1. This form of the disease is the most common and is generally the most mild. 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 prevalent 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 much more severe than the other types. It begins during the first year of life, often developing by 3 months. These babies have brain damage that is extensive and progresses rapidly. In addition to the signs and symptoms listed above, other possible problems that may occur with this type of Gaucher's include:

• Cognitive deterioration, 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:

• Cognitive deterioration, including mental retardation or dementia
• Abnormal eye movements
• Loss of muscle coordination

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

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Autosomal recessive inheritance pattern

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.

The risk of having type 1 or 3 Gaucher's disease or being a carrier is higher if you're of Eastern or Central European (Ashkenazi) Jewish ancestry. Type 2 is 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 of all types
Possible complications of all types of Gaucher's disease include:

• Bone pain, which can become severe and incapacitating and may be associated with fractures.
• A tendency to bleed, which may result in repeated hemorrhaging in the nostrils or nasal cavities, or bruising beneath 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
• Abnormal gait
• 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.

You're likely to start by first seeing your family doctor, a general practitioner or a pediatrician, depending on your age when you are first diagnosed. 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 a doctor who specializes in brain and nervous system disorders (neurologist).

Because appointments can be brief, and there's often a lot of ground to cover, it's a good idea to be well prepared. Here's some information to help you get ready for your appointment, and what to expect from your doctor.

What you can do

• Write down any symptoms you're 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 that you're taking.
• Try to create a family medical history ahead of time. 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 come along, if possible. Sometimes it can be difficult to soak up all the information provided to you during an appointment. Someone who accompanies you may remember something that you missed or forgot.
• Write down questions to ask your doctor.

Your time with your doctor is limited, so preparing a list of questions ahead of time may help you make the most of your time. For Gaucher's disease, some basic questions to ask your doctor include:

• What's the most likely cause of my symptoms?
• Are there other possible causes for my symptoms?
• What kinds of tests do I need? Do these tests require any special preparation?
• What's my prognosis
• What treatments are available, and which do you recommend?
• What types of side effects can I expect 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 that I need to follow?
• 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 Web sites do you recommend visiting?

In addition to the questions that you've prepared to ask your doctor, don't hesitate to ask questions during your appointment at any time that you don't understand something.

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 you first begin experiencing symptoms?
• How severe are your 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?

Making the diagnosis
If your doctor suspects Gaucher's disease or if Gaucher's disease runs in your family, the diagnosis is made by evaluating 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) scans, which use magnetic fields and radio waves to create images, to help your doctor see whether you have an enlarged spleen or liver

Prenatal testing
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 assess the risks and benefits.

Some people with type 1 disease have such mild symptoms that they may not need treatment at all. 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 synthetic 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, and help to resolve blood abnormalities. Children treated with enzyme therapy often experience a growth spurt and weight gain as skeletal abnormalities are moderated.

  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 approach is high-risk, it's performed much 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 the age of 2 years. However, children with type 3 who live into their teens often survive for many more years.

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 their Web site or call 800-504-3189. Additionally, your doctor may know if there are any local support groups in your area.