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 organs, and may cause organ enlargement and bone pain.
Gaucher's disease results from an enzyme deficiency, and sometimes the term "glucocerebrosidase deficiency" is used to describe this condition.
Gaucher's disease is most common in Eastern and Central European (Ashkenazi) Jews. It can occur at any age in life, and affects males and females approximately equally.
Gaucher's disease is named after the French doctor who first described the disease in the 1880s. Treatment for Gaucher's disease may involve enzyme replacement and other therapies.
Symptoms
Signs and symptoms of Gaucher's disease can vary widely from one person to another. Bone pain or a bone fracture is often the first symptom. Gaucher's disease symptoms may include:
Skeletal abnormalities, including thinning of your bones (osteopenia), bone pain and bone fractures
Enlarged liver (hepatomegaly) or spleen (splenomegaly), or both
Anemia, due to fewer healthy red blood cells
Excessive fatigue
A greater susceptibility to bruising, which may mean you have a low blood platelet level (thrombocytopenia)
Cognitive deterioration, including mental retardation or dementia
Yellow spots in your eyes (pingueculae)
Abnormal eye movements
Impaired function of your lungs and kidneys
Brownish coloring of your skin
There are three major types of Gaucher's disease. Classification depends on age at the time of diagnosis, and whether the brain and central nervous system are involved:
Type 1. In this form of the disease, there's no brain involvement. It can occur at any age, although it's most prevalent in adults, with an average age of 20 years old at the time of diagnosis. It's by far the most common type of Gaucher's disease.
Type 2. This form of Gaucher's disease is rare and occurs in infants with severe signs and symptoms, such as liver and spleen enlargement, developing by 3 months of age. These babies have brain damage that is extensive and progresses rapidly.
Type 3. This form of Gaucher's disease, also rare, occurs in children and adolescents. It tends to be chronic and progresses more slowly than does type 2. Although the brain is affected, brain involvement tends to be relatively mild. Signs and symptoms, such as enlargement of the liver and spleen, vary in intensity.
Types 2 and 3 account for only 5 percent of the cases of Gaucher's disease.
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 also within your bone marrow.
Gaucher's disease is passed along in an inheritance pattern called autosomal recessive. Both parents need to be carriers of the Gaucher's genetic mutation in order for their child to develop the condition. But even when both parents are carriers, there's still only a 25 percent chance that the child will develop the disease, compared with a 50 percent chance of their child being an unaffected carrier, and a 25 percent chance of him or her not being a carrier and not having the disease.
Risk factors
If you're of Eastern or Central European (Ashkenazi) Jewish ancestry, and particularly if you have a family history of Gaucher's disease, you have an increased risk of either developing the disease or being a carrier.
When to seek medical advice
If you have any of the signs and symptoms associated with Gaucher's disease, make an appointment with your doctor for an evaluation.
When a family history of Gaucher's disease is present, ask your doctor about having a blood sample withdrawn for genetic testing that can determine if you are a carrier of the genetic defect. Particularly if you're considering having children, you may also be referred to a genetic counselor to evaluate the potential risks to your offspring.
Tests and diagnosis
If your doctor suspects Gaucher's disease or if Gaucher's disease runs in your family, the diagnosis is made by conducting a blood test that evaluates levels of the enzyme associated with the disease.
People with Gaucher's disease have low levels of the enzyme glucocerebrosidase 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.
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 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.
Complications
People with type 2 Gaucher's disease often develop serious neurological complications, including:
Seizures
Abnormal gait
Swallowing problems
As these problems progress and become more severe, they can become debilitating and lead to death. Children with type 2 disease usually die by the age of 2 years.
Other possible complications include:
Severe swelling (edema) at birth, caused by a buildup of fluid in tissues
Calcification of heart valves, damaging the valves and making it increasingly difficult for them to open fully and function properly
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 bleeding beneath the skin (ecchymosis)
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.
Treatments and drugs
To treat 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 at two-week intervals at high doses.
Although effectiveness can vary, it's 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.
This treatment is most effective when started prior to development of significant organ enlargement or bone impairment. 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, triggering a rash, nausea, diarrhea or abdominal pain.
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.
The medication miglustat (Zavesca). The effectiveness of this oral medication in people with Gaucher's disease is still being studied, but it may be capable of interfering with the production of glucocerebrosides in some people with type 1 disease. Diarrhea and weight loss are common side effects.
Prognosis
People with mild cases of Gaucher's disease, particularly those who develop it in adulthood, have normal life expectancies. Children whose illness begins during infancy generally don't live beyond the age of 2 years old.
By Mayo Clinic Staff
Gaucher's disease results from an enzyme deficiency, and sometimes the term "glucocerebrosidase deficiency" is used to describe this condition.
Gaucher's disease is most common in Eastern and Central European (Ashkenazi) Jews. It can occur at any age in life, and affects males and females approximately equally.
Gaucher's disease is named after the French doctor who first described the disease in the 1880s. Treatment for Gaucher's disease may involve enzyme replacement and other therapies.
Symptoms
Signs and symptoms of Gaucher's disease can vary widely from one person to another. Bone pain or a bone fracture is often the first symptom. Gaucher's disease symptoms may include:
Skeletal abnormalities, including thinning of your bones (osteopenia), bone pain and bone fractures
Enlarged liver (hepatomegaly) or spleen (splenomegaly), or both
Anemia, due to fewer healthy red blood cells
Excessive fatigue
A greater susceptibility to bruising, which may mean you have a low blood platelet level (thrombocytopenia)
Cognitive deterioration, including mental retardation or dementia
Yellow spots in your eyes (pingueculae)
Abnormal eye movements
Impaired function of your lungs and kidneys
Brownish coloring of your skin
There are three major types of Gaucher's disease. Classification depends on age at the time of diagnosis, and whether the brain and central nervous system are involved:
Type 1. In this form of the disease, there's no brain involvement. It can occur at any age, although it's most prevalent in adults, with an average age of 20 years old at the time of diagnosis. It's by far the most common type of Gaucher's disease.
Type 2. This form of Gaucher's disease is rare and occurs in infants with severe signs and symptoms, such as liver and spleen enlargement, developing by 3 months of age. These babies have brain damage that is extensive and progresses rapidly.
Type 3. This form of Gaucher's disease, also rare, occurs in children and adolescents. It tends to be chronic and progresses more slowly than does type 2. Although the brain is affected, brain involvement tends to be relatively mild. Signs and symptoms, such as enlargement of the liver and spleen, vary in intensity.
Types 2 and 3 account for only 5 percent of the cases of Gaucher's disease.
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 also within your bone marrow.
Gaucher's disease is passed along in an inheritance pattern called autosomal recessive. Both parents need to be carriers of the Gaucher's genetic mutation in order for their child to develop the condition. But even when both parents are carriers, there's still only a 25 percent chance that the child will develop the disease, compared with a 50 percent chance of their child being an unaffected carrier, and a 25 percent chance of him or her not being a carrier and not having the disease.
Risk factors
If you're of Eastern or Central European (Ashkenazi) Jewish ancestry, and particularly if you have a family history of Gaucher's disease, you have an increased risk of either developing the disease or being a carrier.
When to seek medical advice
If you have any of the signs and symptoms associated with Gaucher's disease, make an appointment with your doctor for an evaluation.
When a family history of Gaucher's disease is present, ask your doctor about having a blood sample withdrawn for genetic testing that can determine if you are a carrier of the genetic defect. Particularly if you're considering having children, you may also be referred to a genetic counselor to evaluate the potential risks to your offspring.
Tests and diagnosis
If your doctor suspects Gaucher's disease or if Gaucher's disease runs in your family, the diagnosis is made by conducting a blood test that evaluates levels of the enzyme associated with the disease.
People with Gaucher's disease have low levels of the enzyme glucocerebrosidase 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.
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 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.
Complications
People with type 2 Gaucher's disease often develop serious neurological complications, including:
Seizures
Abnormal gait
Swallowing problems
As these problems progress and become more severe, they can become debilitating and lead to death. Children with type 2 disease usually die by the age of 2 years.
Other possible complications include:
Severe swelling (edema) at birth, caused by a buildup of fluid in tissues
Calcification of heart valves, damaging the valves and making it increasingly difficult for them to open fully and function properly
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 bleeding beneath the skin (ecchymosis)
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.
Treatments and drugs
To treat 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 at two-week intervals at high doses.
Although effectiveness can vary, it's 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.
This treatment is most effective when started prior to development of significant organ enlargement or bone impairment. 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, triggering a rash, nausea, diarrhea or abdominal pain.
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.
The medication miglustat (Zavesca). The effectiveness of this oral medication in people with Gaucher's disease is still being studied, but it may be capable of interfering with the production of glucocerebrosides in some people with type 1 disease. Diarrhea and weight loss are common side effects.
Prognosis
People with mild cases of Gaucher's disease, particularly those who develop it in adulthood, have normal life expectancies. Children whose illness begins during infancy generally don't live beyond the age of 2 years old.
By Mayo Clinic Staff
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