Gaucher disease

General: People with Gaucher disease have low or non-existent levels of an enzyme called glucocerebrosidase. Enzymes are proteins that bring about a chemical reaction. Glucocerebrosidase is an enzyme needed to break down a fatty substance called glucocerebroside. Glucocerebrosides are fatty carbohydrates that are found in the brain and nervous system. Without the glucocerebrosidase enzyme, glucocerebrosides accumulate in the body and may damage the organs.

Glucocerebrosidase deficiency occurs because people with Gaucher disease inherit a mutated, or abnormal, glucocerebrosidase gene from their parents. Normally, this gene provides instructions on how to make glucocerebrosidase. When the gene is mutated, the body is unable to produce enough of this enzyme.

Inheritance: Each gene has two variations, called alleles. One allele is inherited from each parent. The mutated gene that causes Gaucher disease is passed down as an autosomal recessive trait. This means that two mutated alleles (one from each parent) of a single gene must be inherited in order for a person to have the disorder.

People who only have one mutated allele do not experience symptoms and are called carriers. If only one parent is a carrier, there is a 50% chance with each birth that the child will be a carrier and a 0% chance that the child will inherit the disease. If both parents are carriers, there is a 25% chance that their child will inherit the disease, and a 50% chance that their child will be a carrier.

General: Gaucher disease is typically diagnosed based on the patient's signs and symptoms and blood test results. Although a DNA test can confirm a diagnosis, it is generally not needed because blood tests can detect low levels of glucocerebrosidase. DNA testing may be performed to determine if a person is a carrier. In addition, prenatal DNA testing may be performed if there is a family history of Gaucher disease. Once someone is diagnosed with Gaucher disease, additional tests, such as a dual energy X-ray absorptiometry (DEXA) or magnetic resonance imaging (MRI) scans, may be performed to monitor his/her condition.

Blood test: If Gaucher disease is suspected, a doctor may take a sample of the patient's blood to determine if he/she has a low level of the glucocerebrosidase enzyme. Patients with Gaucher disease have at least 85% less glucocerebrosidase than healthy individuals.

Although carriers do not have symptoms of Gaucher disease, they often have intermediate levels of glucocerebrosidase in their blood. In other words, their glucocerebrosidase levels are somewhere between those of a healthy person and a person with Gaucher disease.

DNA test: If a person has a family history of Gaucher disease, a DNA test may be performed to determine if he/she carries a copy of the mutated glucocerebrosidase gene. Although a carrier does not have Gaucher disease, he/she may pass a copy of the mutated gene to his/her children.

A DNA test may also be performed to confirm a diagnosis of Gaucher disease.

Prenatal testing: If a parent is a carrier of the mutated glucocerebrosidase gene, prenatal testing, such as amniocentesis or chorionic villus sampling, may be performed to determine if the fetus has the disorder. However, there are serious risks associated with prenatal tests. Patients should discuss the potential health benefits and risks associated with these procedures before making any medical decisions.

During amniocentesis, a long, thin needle is inserted through the abdominal wall into the uterus and a small amount of fluid that surrounds the fetus (called amniotic fluid) is removed. This fluid sample is then analyzed to determine if the fetus has the mutated gene associated with Gaucher disease. This test is performed after 15 weeks of pregnancy. Some experts estimate that the risk of miscarriage ranges from one out of 200-400 patients; it is highest when the procedure is done early in pregnancy, before the two layers of fetal membranes have sealed. A woman's particular risk depends in large part on the skill and experience of the doctor performing the procedure. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.

During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the organ that nourishes the developing fetus in the uterus (called the placenta). Depending on where the placenta is located, CVS can be performed through the cervix or through the abdomen. The tissue sample is then analyzed to determine if the fetus has the mutated gene associated with Gaucher disease. This procedure may be performed between the ninth and 14th week of pregnancy. There are slightly more risks involved with CVS than amniocentesis. Miscarriage occurs in about two percent of women who undergo this procedure. There appears to be an even higher risk of miscarriage with the transcervical CVS technique compared to the transabominal technique. Other factors that further increase the risk of CVS include having the procedure performed three or more times and having a fetus that is smaller than normal for their age. The physician's skill and experience also play an important role.

Dual energy X-ray absorptiometry (DEXA): Dual energy X-ray absorptiometry (DEXA) may be performed to measure and monitor the patient's bone density. People with Gaucher disease often develop osteopenia, which causes the bones to become thin and porous. DEXA uses two different X-ray beams to estimate bone density in the spine and hip. Strong, dense bones allow less of the X-ray beam to pass through them. DEXA can measure as little as 2% of bone loss per year.

Bone density results are reported as two numbers: T-scores and Z-scores.

The T-score represents a person's bone density compared to what is considered normal for a healthy adult of the same gender. A T-score of one or higher is considered normal. People that have T-scores between -1 and -2.5 have osteopenia and are at risk of developing osteoporosis. Patients with T-scores lower than -2.5 have osteoporosis.

The Z-score represents a person's bone density compared to a healthy individual of the same gender, age, weight, and racial and ethnic origin. This number may be helpful to determine if the underlying cause is not related to age, gender, weight, or heredity. A Z-score that is less than -1.5 may indicate that other factors are causing bone loss.

Magnetic resonance imaging (MRI) scans: Magnetic resonance imaging (MRI) scans may be performed to monitor for signs of an enlarged spleen or liver. These painless procedures provide images of the internal organs.

General: Symptoms of Gaucher disease vary considerably among patients. In general, glucocerebrosides tend to buildup in the liver, spleen, bone marrow, lungs, and sometimes, the brain. Common symptoms include thinning or hollowing of the bones (called osteopenia), which may lead to bone pain and fractures. Fatigue and an enlarged liver and/or spleen are also common among patients. Additional symptoms depend on the specific organs that are affected.

Type 1 Gaucher disease: Type 1 Gaucher disease typically causes liver and spleen enlargement, bone pain, broken bones, and sometimes lung and kidney problems. Type 1 Gaucher disease does not affect the brain.

Type 2 Gaucher disease: Type 2 Gaucher disease, which is rare, causes severe brain damage and spleen and liver enlargement during the first three months of life that usually leads to death by age two. The baby's brain deteriorates rapidly, causing intellectual disabilities (mental retardation). Babies may experience seizures, difficulty swallowing, decreased motor control, and an abnormal manner of walking. Eventually, the child is unable to control involuntary bodily functions necessary for life. For instance, the child's heart may not beat efficiently.

Type 3 Gaucher disease: Type 3 Gaucher disease, which is also rare, usually develops during childhood or adolescence. This form also affects the brain, but it progresses more slowly than type 2 Gaucher disease, and brain involvement is generally mild. People with type 3 Gaucher disease often have intellectual disabilities or dementia. Additional symptoms may include an enlarged liver and spleen and anemia. The severity of these symptoms varies among patients.

Calcification of heart valves: Without treatment, glucocerebrosides may build up in the heart, causing calcification of the heart valves. This occurs when the accumulation of glucocerebrosides makes it difficult for the heart valves to properly open and close. As a result, it becomes increasingly difficult for the heart to efficiently pump blood throughout the body.

Cancer: It has been suggested that elderly people with Gaucher's disease may be more vulnerable to certain types of cancer, especially a bone marrow cancer called multiple myeloma.

Neurological problems: People with type 2 Gaucher disease experience severe neurological (brain) complications that ultimately lead to death before age two. Common complications include seizures, difficulty swallowing, decreased motor control, and an abnormal manner of walking. Eventually, the child is unable to control involuntary bodily functions necessary for life.

Organ damage: Without treatment, glucocerebrosides may accumulate in vital organs, such as the lungs and kidneys. If left untreated, it may lead to organ dysfunction or failure.

Osteopenia: Gaucher disease typically causes the bones to become hollow and brittle. As a result, people may experience severe bone pain, and they have an increased risk of experiencing bone fractures. Without proper treatment, this pain may interfere with daily activities.

Ruptured spleen: Many people with Gaucher disease have an enlarged spleen. In extreme cases, the spleen may rupture and cause life-threatening bleeding into the abdominal cavity. This is most likely to occur if the person participates in rigorous physical activities when the spleen is enlarged. Patients who rupture their spleens typically experience a sharp and sudden pain in the upper-left side of the abdomen. If this type of pain develops, patients should be taken to the nearest hospital immediately. A ruptured spleen generally requires surgery.

Severe swelling (edema): Infants born with type 2 Gaucher disease may experience severe swelling in one or more parts of the body at birth. This is caused by a buildup of fluid in the body tissues.

Increased bleeding: People with Gaucher disease may have an increased risk of bleeding. This is because the disorder may damage blood-forming cells. As a result, people may experience bleeding in the nose or under the skin.