With Gaucher’s Disease, fatty substances (sphingolipids) accumulate in cells and certain organs. In some cases, people may not know they have it because they have no overt problems. This is a frightening fact, considering Gaucher’s Disease can lead to severe disability and death.
While there are those who show no outward signs of the condition, the common symptoms of Gaucher’s disease are anemia, fatigue, nosebleeds, osteoporosis, bone pain and easily broken bones. Other signs include a swollen stomach due to the enlargement of the liver and spleen and bone infarctions, which often lead to damage to the shoulder or hip joints. The spleen, lungs, brain, metabolism and bone marrow can be affected.
If Gaucher’s disease is suspected, enzyme levels associated with the disease are checked. Individuals with the disease have very low levels of enzyme activity. An enzyme assay test measures glucocerebrosidase (GC) activity in leukocytes, fibroblasts or urine.
Ninety to 95 percent of mutations of the GC gene associated with Gaucher’s disease occur in the Ashkenazi Jewish population (one in 450 has this disorder) who hail from Eastern, Central and Northern Europe. But in the overall population, according to www.genome.gov, the incidence of the disease is between 1 in 50,000 to 1 in 100,00 individuals. It is named for Dr. Philippe Gaucher, a French dermatologist who treated a woman with an enlarged spleen and first diagnosed it in 1882.
There are various types of Gaucher’s disease, which causes fatty materials to accumulate where they shouldn’t in the spleen, liver, lungs, bone marrow and brain. Various treatments exist. The good news is that a blood test can diagnose the disease early in its progression. Carrier status can be detected with analysis of blood or saliva.
Type I Gaucher’s disease is the most common. It is non-neuropathic because the brain and spinal cord are usually not involved. Symptoms of this type include an enlarged liver and spleen, a low number of red blood cells, easy bruising caused by a decrease in blood platelets, lung disease and bone abnormalities including bone pain, fractures and arthritis.
Types 2 and 3 of Gaucher’s disease are neuronapathic forms of the disorder, characterized by problems of the central nervous system. The condition can cause abnormal eye moments, seizures and brain damage. People with Type 3, with progressive neurological symptoms appearing later in childhood, worsen more slowly than those with Type 2. Lack of coordination, mental deterioration and seizures characterized by brief shock-like jerks of a muscle or group of muscles may result.
There is also a subclassification type 3 called Norbotthian Gaucher’s Disease, during which slowly progressive neurologic symptoms may not occur until early childhood. No effective treatment exists for people with types 2 or 3 who have severe brain damage, according to the National Institute of Neurological Disorders and Stroke, which is part of the National Institutes of Health.
The most severe manifestation of the disease is the perinatal lethal form, occurring before birth or in infancy. It features extensive swelling caused by fluid accumulation before birth, dry and scaly skin or other skin abnormalities, distinctive facial features, and severe neurological problems. Most infants with this form survive only a few days, but some live approximately two years. Unfortunately, there is no known treatment for this type of the disease.
Also serious is the cardiovascular type of Gaucher’s disease, which causes heart valves to harden. People with this form of the disease may also have eye abnormalities, bone disease and mild spleen enlargement.
There are effective treatments for some variants of the disease. Enzyme replacement therapy is administered intravenously for the non-neurological presence of types 1 and 3 of Gaucher’s disease. Those with Type 1 may undergo substrate reduction therapy, which works by reducing the amount of glucosylceramide, or GL1, that a cell makes. Oral medication may be prescribed for those 18 and older or those with mild cases. Treatments can include pain reduction therapies, blood transfusions, orthopedic surgery for bones and joints, and, in rare cases, a splenectomy or spleen removal.
Because living with Gaucher’s disease is stressful, psychological care may be recommended. This metabolic disorder can exert a mental and emotional toll and patients and their families, who can help their loved ones make lifestyle changes, if they are needed. Some people experience severe pain and fatigue. For them, using crutches or a wheelchair for mobility may be the right answer. Seek support from the National Gaucher Foundation to learn more about the disease, treatments, and coping strategies.
A genetic disease specialist is recommended to monitor the progress of Gaucher’s disease and lead medical decisions. But a person with the disease may see many doctors because it affects many different parts of the body. Research and clinical trials relating to Gaucher’s disease are proceeding to develop additional means of treatment and/or a cure, including cell and gene therapy.
One researcher investigating Gaucher’s disease is Dr. Ellen Sidransky, Senior Investigator and Head of the Molecular Neurogenetics Section at the Medical Genetics Branch of the National Human Genome Research Institute in Bethesda, Maryland. Having studied the disease for two decades, she is now focused on why each mutation can produce a wide array of symptoms. Patients with similar symptoms can have very different genetic mutations. Patients with the same genetic mutation can experience very different symptoms. She says the disease is “proving more complex than I ever anticipated.”
Dr. Sidransky hopes to unlock the puzzle of the disease, which will have wide-ranging effects on other conditions. She says it “will give us a window into more complicated genetic problems and a whole range of more common genetic disorders.”