Gaucher’s disease can’t be cured, but treatment can help control symptoms. Drugs replace the missing enzyme and can reduce spleen size, improve bone pain, and lower low platelet counts (thrombocytopenia).
Gaucher disease is an autosomal recessive disorder caused by defective activity of the lysosomal enzyme acid beta-glucocerebrosidase. The defect leads to excessive accumulation of glucocerebroside, which causes hepatosplenomegaly, anemia, and thrombocytopenia.
Symptoms
In Gaucher disease, the body lacks an enzyme that breaks down a type of fat in the blood called glucocerebroside. Without this enzyme, glucocerebroside builds up in cells and causes them to enlarge. Over time, this can cause a swollen (enlarged) liver and spleen. The swollen organs can interfere with a person’s ability to eat or absorb nutrients, and they can also block the passage of blood through the body. Gaucher disease is one of several diseases known as lysosomal storage disorders. Others include Pompe, Hunter, and Fabry diseases.
Symptoms of Gaucher disease vary from person to person. They may start in childhood or early adulthood and range from mild to severe. Some people have no symptoms at all, while others have serious ones that can lead to a shorter life expectancy.
The most common symptoms of Gaucher disease are an enlarged spleen and liver (splenomegaly), bone disease, and low platelet and hemoglobin levels. Some people with this condition also have eye problems and a change in the shape of the femur bone (osteoporosis).
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In type 1 Gaucher disease, also called non-neuronopathic Gaucher disease, a toxic buildup of glucocerebroside collects inside cells of the body, including the spleen and liver. This form of the disease can be fatal, especially in infants, because it affects the nervous system. It is the most common form of Gaucher disease.
Type 2 Gaucher disease is less common than type 1 and is more severe. It affects the nervous system, and the first symptoms usually appear by a baby’s 3rd month of life. Often, the spleen and liver become enlarged, which can interfere with a child’s growth and development.
Type 3 Gaucher disease has a more gradual onset than type 2. It can be managed, and many people live into middle age. However, it leads to a shortened life expectancy because the affected person’s enzyme isn’t working properly. Some people with this form of the disease are not able to live independently because they can’t walk or use their hands. They may need help bathing and using the toilet, dressing, eating, and moving around.
Diagnosis
The most common symptoms of Gaucher disease are an enlarged liver and spleen (hepatomegaly) and low platelet counts (thrombocytopenia). People with Gaucher disease also develop bone disease and can have problems breathing and digesting food. They can also experience myoclonic seizures. Signs and symptoms vary greatly from one person to the next, even within the same family.
The diagnosis is usually made by a blood test that measures the activity of the enzyme glucocerebrosidase in your leukocytes (white cells). Generally, less than 15% of normal activity is diagnostic for Gaucher disease. This test is available through major laboratories, e.g. Counsyl, Labcorp or Quest Diagnostics, and at some hospitals or doctor’s offices. It can be used to help diagnose the different types of Gaucher disease, as well as to identify carriers – people who do not have the disease but will pass on the defective gene to their children.
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A bone marrow test may be helpful in diagnosing Gaucher disease, but this is rarely required. The marrow test can show fat-laden Gaucher cells that aren’t seen on routine blood tests, but it is not always accurate in identifying Gaucher cells. This test is not commonly done because the risk of complications from the test outweighs its benefits.
If you have a high risk for Gaucher disease, based on your family history or your ethnicity, a genetic test can be performed to determine whether or not you have the defective GBA gene. Having the genetic test will allow you to know if you are a carrier of Gaucher disease, and it will also help your doctor decide when you should begin treatment.
If you are of Eastern and Central European Jewish (Ashkenazi) ancestry, your doctor may recommend that you be tested for Gaucher disease. This is because the type 1 form of the disease occurs most often among this group, and because a number of other hereditary blood disorders are linked to this ancestry, including Pompe, Hunter and Hurler diseases. It’s important to get a prompt diagnosis because treatment can reduce the severity of symptoms and prevent complications.
Treatment
Treatment for Gaucher’s disease focuses on controlling symptoms and slowing progression of the disease. It can include enzyme replacement therapy, which replaces the missing glucocerebrosidase, and drugs that limit production of fatty chemicals (cytokine inhibitors).
Enzyme replacement therapy is most effective for Type 1 Gaucher disease, which affects mostly people of Ashkenazi Jewish descent. It can reduce the enlarged spleen and liver, improve anemia, and raise platelet count (thrombocytopenia). It also can ease bone pain and prevent severe bone crises.
ERT is given through an IV at a hospital or clinic. It’s typically administered monthly or every other week for people of all ages.
In children with type 2 Gaucher disease, treatment can delay the onset of serious complications in childhood, and improve cognitive functioning. It can also help with growth and development and correct delayed puberty.
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Patients with type 3 Gaucher disease may develop serious problems such as hepatitis and spleen problems, but not as often as in types 2 and 1. The condition can interfere with the blood supply to bones, causing them to break down or die. People with this form of Gaucher disease can live into adulthood.
There is a new oral prescription medication for type 1 Gaucher disease called Zavesca. It’s taken twice a day. This is a good option for adults who don’t respond to or cannot take ERT. It is important to get regular follow-up exams with your doctor and have tests like MRI or CT scans to check for signs of the disease.
Research continues to explore ways to slow the progression of the disease, and find better therapies for the different forms of Gaucher disease. Some people with the disease have an increased risk of certain cancers, such as pancreatic cancer and melanoma. They may also have a higher risk of multiple myeloma or non-Hodgkin lymphoma. They may also have an increased risk of Parkinson’s disease. These risks are based on family history and ethnic background. People with Gaucher disease should avoid alcohol and tobacco, because these can worsen the symptoms of the disease.
Prevention
The genetic mutation that causes Gaucher disease affects how the body responds to certain substances, which cause a variety of signs and symptoms. However, the signs and symptoms can vary from person to person. This is called phenotypic expression. It is thought that environmental factors, in addition to a person’s particular genetic mutation, influence whether symptoms appear and how severe they are.
Signs and symptoms of Gaucher disease can begin at any age, but the most common form (type 1) usually starts in childhood or adolescence. It can cause anemia, easy bruising, enlarged liver and spleen, breathing problems, and bone pain. This type of Gaucher disease also causes a decrease in blood platelets (thrombocytopenia) and abnormalities of the liver, lungs, and kidneys. Some people with this type of Gaucher disease may develop neurological signs such as eye movement disorders, muscle rigidity, swallowing difficulties, seizures, and dementia.
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Other forms of Gaucher disease are less common. Type 3 appears in the same way as type 1, but symptoms usually don’t start until adulthood. People with this form of the condition have a more rapid progression and are more likely to have brain damage. One rare subtype of Gaucher disease, known as perinatal lethal Gaucher disease, occurs in infancy and is fatal either before birth or soon after.
A doctor can diagnose Gaucher disease based on symptoms, a physical exam, and lab tests. A blood test can measure the activity of a specific enzyme in the body that is affected by Gaucher disease, called glucosylceramidase. Genetic testing for the four most common mutations associated with Gaucher disease can help identify people at risk.
People with a family history of Gaucher disease should talk to a genetic counselor about their risk for having the condition and their chances of passing it on to their children. If both parents have a changed (mutated) copy of the gene, each child has a 1 in 4 chance of developing the most common form of the disease. Prenatal screening for Gaucher disease can also be done to determine if a baby is at risk for having the condition.
