Gaucher disease: The most common lysosomal storage disorder.
What is the basis of Gaucher disease?
The human body contains specialized cells called ‘macrophages’ that remove worn-out cells by degrading them to simple molecules for recycling – a process which is analogous to eating and digesting food. The macrophages ‘eat’ worn-out cells and then degrade them inside cell compartments called lysosomes that serve as the ‘digestive tracts’ of cells. The enzyme glucocerebrosidase is located within the lysosomes and is responsible for breaking down glucocerebroside into glucose and a fat called ceramide.
People with Gaucher disease lack the normal form of the glucocerebrosidase enzyme and are unable to break down glucocerebroside. Instead, the glucocerebroside remains stored within the lysosomes, preventing the macrophages from functioning normally. Enlarged macrophages containing undigested glucocerebroside are called Gaucher cells. These cells are the hallmark of this disease. Gaucher disease is the most common of 10 so-called "storage" disorders – the most widely known being Tay-Sachs disease.
What happens when Gaucher cells accumulate?
Gaucher cells most often accumulate in the spleen, liver, and bone marrow. However, they may also collect in other tissues, including the lymphatic system, lungs, skin, eyes, kidney, heart, and in rare instances, the nervous system. Frequently, an organ that contains Gaucher cells becomes enlarged and does not function properly, resulting in clinical symptoms associated with the disease. The type and severity of symptoms can vary widely among individuals, from experiencing no symptoms, to developing life-threatening conditions. Click here to see how Gaucher disease affects various parts of the body.
Gaucher cells in the spleen
One of the most common sites for accumulation of Gaucher cells is the spleen. Typically, the effects of Gaucher cell accumulation in this organ cause it to become enlarged and overactive, and may cause the abdomen to become distended so that a person appears overweight or looks pregnant. Normally, the spleen breaks down old blood cells at the same rate that new ones are produced in the bone marrow. When the spleen becomes overactive, it tends to break down red cells more rapidly than they can be produced and a deficiency develops which results in anaemia. Red cells carry oxygen from the lungs to all cells in the body so because anaemic patients lack sufficient red cells, they suffer from the effects of insufficient oxygen. As a result, muscle cells cannot produce the energy they need, and the tendency is to become easily fatigued.
Over-activity of the spleen can also cause a deficiency of white blood cells which can reduce the body's ability to fight bacterial infections. Additionally, it can reduce the number of blood platelets. A reduction in platelets lowers the body’s ability to form blood clots, increasing the tendency for bleeding and bruising. As a result, frequent and heavy nosebleeds are common in people with Gaucher disease.
Gaucher cells in the liver
The liver is another frequent site for Gaucher cell accumulation. The liver can become enlarged and function abnormally and in some individuals, the liver enlarges along with the spleen. In patients who have had their spleens removed, the liver may become dramatically enlarged due to the displacement of Gaucher cell accumulation from the spleen to the liver. The effects of abnormal liver function are usually minor, although a few people may develop cirrhosis where the liver develops scar tissue.
Gaucher cells in the bone marrow
Another common site where Gaucher cells collect is the marrow inside bones of the skeleton. The accumulated Gaucher cells reduce normal bone marrow function in the areas where the Gaucher cells are most concentrated. This can lead to the variety of bone problems that are commonly found in people with Gaucher disease. For example, Gaucher cells in the bone marrow can interfere with the production of blood cells (the marrow is one of the normal sites in the body where blood cells are formed), compounding the deficiencies caused by an overactive, enlarged spleen.
Bones affected by Gaucher disease may be more prone to infection. The bones may be thinner or weaker than normal, or they may be deformed. In addition, "bone crises" can occur when there is a sudden lack of oxygen in an area where Gaucher cells have interfered with normal blood flow. These episodes can be extremely painful, feeling like a "heart attack of the bone." The restriction in blood flow can also result in destruction of bone tissue (called aseptic necrosis) and can lead to permanent mobility problems.
In addition, the bones may become brittle and subject to spontaneous fractures. If these fractures occur in the spinal column, they are called compression fractures and can cause nerve damage. Individuals with Gaucher disease often complain of general bone and joint pain. This pain is most likely due to inflammation in the skeletal system caused by the presence of Gaucher cells.
Is there a typical Gaucher individual?
Although all people with Gaucher disease lack normal levels of glucocerebrosidase activity, there is a variation from person to person. As a result, the timing and severity of symptoms vary greatly. At present, Gaucher specialists divide the disease into three classifications: Types 1, 2, and 3, based on the particular symptoms and course of the disease. Generally speaking, the later in life the first symptoms appear, the less likely that the disease will be severe.
Gaucher Disease Discoverer
Philippe Charles Ernest Gaucher (July 26, 1854 - January 25, 1918) was a French dermatologist born in the department of Nièvre.
He received his medical doctorate in 1882, and soon after headed a medical clinic at Necker Hospital. During the subsequent years he was an instructor at several hospital clinics in Paris. He taught classes on pathological anatomy, bacteriology and histology, as well as dermatology. In 1902 he succeeded Jean Alfred Fournier (1832-1914) as the university chair of dermatology and syphilography. Gaucher was also founder of a journal on venereal disease called Annales des Maladies Vénériennes.
Gaucher is remembered for his description of the disorder that was to become known as Gaucher disease. In 1882 while still a student, he discovered this disease in a 32-year old woman who had an enlarged spleen. At the time, Gaucher thought it to be a form of splenetic cancer, and published his findings in his doctorate thesis titled "De l'epithelioma primitif de la rate, hypertrophie idiopathique de la rate sans leucemie". However, it wouldn't be until 1965 that the true biochemical nature of Gaucher disease was understood.