Gaucher's disease is a rare, genetic disorder in which abnormal amounts of glucocerebroside (a lipid substance or fat) is deposited in cells and vital organs that are normally lipid-free or have a lower lipid content. These organs include the spleen, kidney, lungs, bone marrow, the liver and the brain. It is the most common lysosomal storage disease.
The lysosome is an organelle (part of a cell) that functions as a trash disposal and processing unit by breaking down unwanted substances with the use of enzymes. When the lysosome functions abnormally, these unwanted substances build up in the cell structures and cause dysfunctional cell activity.
There are three subtypes of Gaucher's disease grouped according to their symptoms. Type 1 is the mildest and more common, occurs in 90% of the cases and is more prevalent in adults, although it may appear at any age. There is usually no damage to the brain but can have some complications to vital organs.
The type 2 is much more severe and rare. The first symptoms often appear before the first year of life, usually at three months of age. The affected child develops brain complications like seizures and rigidity that progresses rapidly leading to death at around two years of age. No treatment or management is available.
Type 3 is also rare, and like type 2, causes brain damage, but at a slower pace and during a longer time, with milder complications. It usually begins at childhood or even later and the patient may survive teenage years or even a fraction of adulthood.
Patients suffering from Gaucher's disease have inherited a defective gene from both parents. The gene is located in chromosome 1 and the defect (mutation) causes the gene product to malfunction.
The condition affects males and females with similar frequency. It is estimated that 1% of the United States population are carriers of the defective gene. Carriers have only one copy of the defective gene and do not display symptoms. The carrier rates are high among ethnic groups from eastern and central Europe like Ashkenazi Jews.
In Gaucher's disease, there is a deficiency of the enzyme glucocerebrosidase which is responsible for breaking down a fatty substance called glucocerebroside. The defect in this enzyme causes glucocerebroside to accumulate in cells, and specifically, in the white blood cells. The white blood cells circulate through the whole body and are particularly frequent in the organs because they are recruited to fight pathogens. Too much lipids and lipid-filled white blood cells in organs causes their malfunction. Dysfunctions may include: enlarged spleen and liver, kidney stones, swelled nymph nodes, neurologic damage, eye problems and problems in blood production.
- Bone problems like osteoporosis, bone pain and increased risk of fractures
- Enlarged abdomen due to swollen liver and spleen
- Anemia and excessive fatigue
- Increased tendency of bruising due to low platelet count
- Yellow spots in the eyes due to accumulation of fat
- Frequent nosebleeds
- Stunted growth and delayed puberty
- In babies, poor ability to suck and swallow
- Serious seizures and body rigidity
- Mental deterioration and apnea
- Enlarged abdomen due to swollen spleen and liver
- Seizures, convulsions and poor coordination
- Skeletal problems, osteoporosis and bone pain
- Eye movement disorders like strabismus and squinting
- Mental retardation and dementia
- Loss of body coordination
The definite test for Gaucher's disease is genetic testing that can be done both on the parents and on the developing fetus before it matures. Blood tests can be done to determine glucocerebrosidase levels; preliminary diagnosis of Gaucher's disease is supported by low-levels of this enzyme.
Genetic mutation analysis could be performed to probe for existence of altered genes and identify carriers. Further genetic tests can identify which type of Gaucher's disease is present. For the fetus, the amniotic fluid and blood from the umbilical cord is extracted via ultrasound-guided injection.
Tests are also done to track progression of the disease, like bone scans to check bone integrity, computerized tomography (CT) and magnetic resonance imaging (MRI) scans to check the whole body for fat deposits and organ enlargement. Neurological tests are done to assess brain function and coordination.
To present, there is no cure for Gaucher's disease and the goal of current management techniques is to address the symptoms. However, enzyme replacement therapy has shown to be highly effective in reversing manifestations of the disease in the organs of type 1 and type 3 patients. These agents first became available in 1991 from glucocerebrosidase in human placenta and in 1994 from a protein expression system using Chinese hamster ovary cells. Today, the annual cost of enzyme replacement therapy is in the order of a few hundred dollars per person. Examples of enzyme replacement therapy agents are: imiglucerase, velaglucerase alfa and miglustat.
Because of numerous complications from Gaucher's disease, the help of several specialists is needed to manage the disease.
Bone marrow transplant addresses non-neurological symptoms of the disease, but it has such a small success rate that it is performed in very few patients. Blood transfusion, spleen removal, liver transplant, joint replacement, anti-seizure medicines and antibiotics are treatment options available to the Gaucher's disease patient.
Since Gaucher's disease has so many complications, a patient may have several types of systemic problems that can be fatal if not addressed. The survival rate depends on the disease type. Type 2 has poor prognosis while type 1 and 3 can be addressed and survival is good if neurologic symptoms are controlled early on.
Given the genetic nature of this disease, nothing can be done to prevent it. Individuals that might be carriers of the disease (ie. have relatives that suffered from the disease) should seek genetic testing before deciding to have a baby.
Because the disease is so debilitating and distressing, the patient or family are encouraged to seek the help of an organization or support group for Gaucher's disease. Emotional, financial and medical support are important components of a treatment plan. In cases of liver and spleen enlargement, the patient should avoid intense physical contact as it may lead to bleeding.
Because of the high cost of enzyme therapy with risk for allergic complications and development of antibodies against the medical enzymes, research is underway to develop treatment approaches that are cheaper and fully immunocompatible. Very recently, an enzyme called velaglucerase alfa made from human cells, has become available on the market.