Gaucher's Disease Research Paper

“Signs and symptoms of Gaucher’s disease can vary wildly. Siblings, even identical twins, with the same disease may have different levels of severity” (Mayo Clinic). While many people who get the disease can live long lives, most infants who get the disease die by age 1 (Vance). Gaucher’s disease is a rare genetic disorder that results in the buildup of cerebrosides, a type of fatty molecule, eventually causing damage to the spleen, liver, central nervous system, and bones. There are four types of Gaucher’s disease. Type I can occur at any age, but typically averages about age 21. Type I is non-neuropathic, meaning thee nervous system remains unaffected. It does, however, cause “excessive growth of the liver and spleen …, weakening of bones”,
anemia, and periodic spikes of bone pain (Vance). Type II begins its onset during infancy (Vance). Type II is neuropathic, often leading to death within two years (Mayo Clinic). Type II also causes intellectual disability, poor coordination, and muscle weakness (Ihler). Type III is perhaps the worst of the three main types, as it is the combination of type I and type II. Type III onset occurs during childhood. Those with type III survive somewhat longer than those with type II, but not nearly as long as type I. Finally, perinatal lethal form occurs before a child is born. It is characterized by swelling which is caused by fluid buildup before birth. This causes distinctive facial features, severe neurological problems, and ichthyosis, which is dry or scaly skin (Genetics Home Reference). While each of the different types of Gaucher’s disease varies wildly in its symptoms, they all stem from the same problem.
Gaucher’s disease is caused by a lack of the glucocerebrosidase (or GC) enzyme (Vance). Glucocerebrosidase works to facilitate the breakdown of the monosaccharide glucocerebroside. Without the GC enzyme to break it down, glucocerebroside begins to build up. Macrophages are large cells whose purpose is to consume and break down a foreign substance. Because glucocerebroside is acquired by breaking down foreign substances, Gaucher’s disease affects macrophages such as those in the spleen, liver, and bones, causing a buildup of glucocerebroside in their lysosomes
(Vance). Gaucher’s disease is diagnosed in three ways. First, genetic testing can be done to see if both of the parents are carriers. If they are, then there is a one in four chance the child has some form of the disease. Second, the blood of the patient can be tested to see the levels of the GC enzyme. Patients are typically diagnosed if the enzyme is below 30% of its normal level. Also, the buildup of glucocerebroside in cells causes them to swell. By looking at a tissue sample under a microscope, swelling is evident, allowing a patient to be diagnosed (Vance). Gaucher’s disease is a genetic disease, so there is no curing it.
However, there are several methods to prevent the spread of the disease. Gaucher’s disease is caused by damage to the glucocerebrosidase gene on chromosome 1. The disease is autosomal recessive, meaning the trait must be inherited from both parents (Mayo Clinic). Therefore, two carriers have a 50% chance of their child being a carrier, and a 25% chance of having a child with the disease. Luckily, there is a way to prevent the disease from being spread. Couples can have DNA testing done to see if they are carriers of the disease. If they are carriers, but still want to have children, pre-implantation genetic diagnosis is available. In pre-implantation genetic diagnosis, a fetus is tested for the disease before being implanted into the uterus, thus insuring a healthy child. Should the disease be discovered after birth, however, ther are several options for
treatment. Gaucher’s disease can be treated in a variety of ways. Enzyme replacement therapy is often used. Enzyme replacement therapy is a treatment where placentas or DNA manufacturing is used to produce the GC enzyme, which is then administered intravenously to the patient. There are several downsides, however. First, the cost is massive, ranging from one-hundred thousand to four-hundred thousand dollars per year. In addition, it requires treatment to be personalized and its effectiveness with type III remains unknown (Valence). Second, medication can be taken that prevents the creation of more of the problem substances, specifically the glucocerebrosides themselves (Mayo Clinic). Another option is to treat the symptoms, rather than the cause of the problem. Orthopedics to treat bone pain; analgesics for pain; vitamins, iron, blood, or bone marrow transfusions for anemia; and surgical removal of the spleen could all be used in conjunction of combat the various symptoms of Gaucher’s disease (Valence, Mayo Clinic). While treating patients for the disease, doctors can run several tests to keep an eye on the progression of the disease. Routine checks include blood tests for GC enzyme levels, MRIs to view inflation in the liver and spleen, and dual x-ray absorptiometry checks for bone density. Gaucher’s disease is wildly varies in its lethality between its many forms. Type I is the most common of the three major types. Type I is the most common disease affecting the Ashkenazi Jewish people, affecting about one in every four-hundred fifty people, with about one in every ten or fifteen being a carrier . It makes up a total of about 94% of all people diagnosed with Gaucher’s disease. Type II and III do not have a major genetic link, although type II may be more common in those of Swedish descent. Type II affects about one in every one-hundred thousand people, and type II affects about one in fifty-thousand (Ihler). Type I affects the life expectancy of a patient, but by far less that the other types, only lowering life expectancy by about nine years (Winrab). Type II patients typically die between the ages of one and four, while Type III patients typically die between the ages of fifteen and thirty (Genetics Home Reference, Ihler). Those with the perinatal type who manage to survive to birth will only survive for a few more years (Genetics Home Reference). Treating Gaucher’s disease is a major problem that deserves more attention. It is either incredibly expensive or targeted only to symptoms. In some cases, the effectiveness of the treatments are unknown due to a lack of comprehensive data from before the treatments were administrated. There have been many recent progressions that will improve the lives of those with Gaucher’s disease. Future therapies are becoming available that may help to restore damaged brain tissue for those with types II and III (Bates). In addition, the entirety of chromosome 1 was published in 2006, giving researchers more information about the cause of the disease and allowing doctors to know what the damaged gene, so as to prevent its transmission to a child (“Major Events in the U.S.”). In the future, I propose that work on the disease be focused on new ways to prevent the transmission of the disease and furthering research on reconstructing the brain. I believe that the merit of these focuses is important not only to help those with Gaucher’s disease, but also due to their ability to become applicable to other types of diseases.