Gaucher’s disease results from a hereditary enzyme deficiency. It can lead to a range of symptoms, including a swollen abdomen, anemia, and a susceptibility to bruising.

Gaucher’s is a lysosomal storage disorder (LSD). It is the most prevalent out of almost 50 LSDs that have been identified.

Other names for Gaucher’s disease are Gaucher disease, or glucocerebrosidase deficiency. It is pronounced “go-shays.”

The condition is thought to affect between 1 in 50,000 and 1 in 100,000 people. Less than 1 percent of the population in the U.S. are carriers for type 1 Gaucher’s disease.

Between 1 in 500 and 1 in 1,000 infants born to Ashkenazi Jewish parents has Gaucher’s disease. The carrier rate among this population is around 1 in every 14 people.

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Gaucher’s disease involves a mutation on chromosome 1.

A person with Gaucher’s disease lacks an enzyme, or protein, known as glucocerebrosidase.

Glucocerebrosidase breaks down a type of fat, or lipid, known as glucosylceramide, or glucocerebroside, into sugar and simple fats to be used for energy.

If the lipid is not broken down, it will start to collect inside the cells of the brain, bone marrow, lungs, spleen, and liver. These organs will not be able to function properly.

The lipid can also collect in the macrophages, a type of white blood cell.

Glucocerebrosidase exists in lysosomes, sac-like structures inside the cells. Lysosomes break down unwanted substances into simpler ones, so that the cell can use them to make new material or expel them.

If the enzyme that breaks down the waste product is lacking, waste builds up in the cells.

If too much waste builds up, the cells will no longer work properly. Serious health problems can result.

Other lysosomal storage diseases (LSDs) include Pompe, Hunter, Fabry, and Hurler diseases.

There are three types of Gaucher Disease. The main signs and symptoms are an enlargement of the liver and spleen, bone disease, and a low platelet and hemoglobin count, but not everyone will have the same symptoms.

The most common sign is an enlarged spleen, called splenomegaly. This may cause no discomfort to the individual, or it may cause the abdomen to become swollen, full, or painful.

It can also cause platelet and red blood cell dysfunction, because the spleen is a processing center for these cells. Low platelet and red blood cells in the body cause fatigue, easy bruising and bleeding.

Type 1

This is the most common type. It accounts for around 9 in every 10 cases. The symptoms tend to be less severe, and the disease does not affect the brain.

The severity of symptoms and the age of onset differ between individuals. Diagnosis can occur in childhood or adulthood.

Signs and symptoms include:

  • anemia, leading to fatigue and a lack of energy and stamina
  • thrombocytopenia, or low blood platelet numbers, leading to nosebleeds
  • osteoporosis can lead to bone pain, bone thinning, widening of bones above the knee joint, and damage to joints, especially in the hips and shoulders
  • liver damage, including an enlarged liver and pingueculae, or yellow spots in the eyes

Other problems include:

  • delayed puberty
  • enlarged spleen
  • lung problems

Low platelet numbers can make it easy for a person to bruise and bleed, because it takes a long time for the blood to clot.

Type 2

Type 2 is the rarest and most severe form of Gaucher’s disease. It has the same symptoms as type 1, but it affects the nervous system, too.

This type is also known as the acute infantile neuronopathic form and accounts for 1 in 20 cases of the disease.

It involves brainstem abnormalities and serious and rapidly progressing brain damage. Signs and symptoms typically appear at the age of 3 to 6 months.

In addition to the signs and symptoms seen in type 1, type 2 may involve:

  • poor development
  • apnea, where breathing stops temporarily during sleep
  • seizures and jerking movements
  • rigidity
  • difficulty sucking and swallowing

This is a fatal form of Gaucher’s disease, and most children do not survive beyond 2 years of age.

Type 3

This form is rarer than type 1, but more common than type 2.

Signs and symptoms usually appear during childhood or adolescence and progress more slowly than in type 2. It is often called chronic neuronopathic Gaucher disease.

Brain damage is possible, but not as severely as in type 2.

In addition to the signs and symptoms of type 1, type 3 may involve:

  • delayed cognitive development
  • seizures
  • dementia
  • convulsions
  • abnormal eye movements
  • muscle twitches
  • poor coordination

Norbottnian Gaucher’s Disease is a kind of type 3. Symptoms may not become evident until young adulthood.

Perinatal lethal Gaucher’s disease is the most severe type. Complications arise before birth or during infancy. Symptoms include extensive swelling, skin and neurological problems. It is normally fatal either before birth or a few days after.

Gaucher’s disease happens because of a recessive mutation in a gene called GBA. GBA is located on chromosome 1.

Humans normally have two copies of the genes that tell the body to produce the enzyme glucocerebrosidase, and both copies work correctly.

If one copy is faulty, the person will not develop Gaucher’s disease, because just one functioning gene can produce enough of the enzyme.

The person with one faulty gene will not get sick, but they will be a carrier. They can pass on the gene.

If both parents are carriers, a child will have a:

  • 25 percent chance of inheriting two faulty genes and having Gaucher’s disease
  • 50 percent risk of inheriting one faulty gene and being a carrier
  • 25 percent chance of inheriting no faulty genes and neither having Gaucher’s disease nor being a carrier

A carrier can pass on the gene but not necessarily the disease.

If signs and symptoms suggest that Gaucher’s disease may be present, or if there is a family history, the doctor will refer the individual to a genetic specialist.

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Genetic testing can help to confirm a diagnosis.

Blood tests can identify low levels of glucocerebrosidase.

Genetic testing looks for the four most common genetic mutations, N370S, L444P, 84gg and IVS2[+1], and some less common ones.

This test is not completely reliable because the whole range genetic mutations that may be linked with Gaucher’s disease are not yet known.

Genetic testing for these four mutations is between 90 and 95 percent accurate in diagnosing Gaucher’s disease in the Ashkenazi Jewish population, and 50 percent to 60 percent accurate in the general population.

Genetic testing combined with the enzyme test helps diagnose Gaucher’s disease accurately.

If a woman with one faulty gene becomes pregnant, prenatal screening can help predict whether the fetus is likely to have the condition.

Genetic testing before conception can predict a couple’s chances of having a child with Gaucher’s disease. Those with a family history of the condition and those of Ashkenazi Jewish descent may wish to ask about genetic counseling.

There is no cure for Gaucher’s disease, but treatment can help decrease symptoms and improve quality of life.

For patients with type 2 Gaucher’s disease, enzyme replacement therapy is available, but there is no effective treatment for the severe brain damage that is likely to occur.

Some patients with mild type 1 may not need treatment, but they should be periodically monitored.

For patients with type 1 or 3 Gaucher’s disease, a number of therapies may help.

Enzyme replacement therapy (ERT)

This treatment replaces deficient glucocerebrosidase with intravenous recombinant glucocerebrosidase, or imiglucerase.

ERT can help many patients with type 1, and some with type 3.

It can prevent enlargement of the liver and spleen and improve bone density blood platelet count. The main goal is to reduce symptoms and try to prevent irreversible complications.

ERT does not treat nervous system problems, for example brain damage, in patients with types 2 and 3.

Substrate reduction therapy (SRT)

SRT aims to reduce the production and buildup of substrate, or waste material, in cells.

It reduces the amount of waste a cell makes by decreasing the production of glucocerebroside, the substrate for the deficient enzyme.

Miglustat, or Zavesca, is approved by the United States Food and Drug Administration (FDA) as an oral prescription medication for adults with mild to moderate type 1 Gaucher’s disease.

The makers of the drug advise that patients use Zavesca only if they cannot be treated with ERT.

Patients should either have never received ERT or have stopped using it for at least 6 months.

A woman should not use Zavesca if she plans to become pregnant or while she is pregnant or breastfeeding.

Bone marrow transplant

A bone marrow transplant, also known as a stem cell transplant, replaces bone marrow that has been damaged by Gaucher’s with healthy bone marrow stem cells.

Bone marrow is a spongy tissue found in the hollow centers of some bones. Bone marrow cells produce blood cells, including red and white blood cells, and platelets. Platelets help stop bleeding.

Bone marrow transplantation is only used in severe cases of Gaucher’s disease. There is a risk of serious complications, including infection and rejection.

Gaucher’s is a progressive disease, which means it develops gradually. Complications will depend on what type of symptoms the person has, and how severe they are.

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Gaucher’s disease may increase the risk of liver cancer.

Osteoporosis can lead to an increased risk of fractures, pain, and other problems, and the higher risk of bleeding can also have an impact on different aspects of health.

Some additional complications may occur.

Cancer: there may be a higher risk of developing pancreatic cancer, malignant melanoma, and non-Hodgkin lymphoma, according to research published in JAMA, but no increased risk of other types of cancer. The National Gaucher Foundation suggests there is an increased risk of myeloma and hepatocellular carcinoma, or liver cancer.

Parkinson’s disease: there may be a link with Parkinson’s, according to a study published in Autophagy.

Complications linked with type 2 Gaucher’s can be severe.

They include:

  • dysphagia, or difficulty swallowing
  • problems with walking
  • seizures

These problems get worse and can ultimately be fatal.

The most common complication for patients with type 3 Gaucher’s disease is calcification of the heart valves, leading to aortic stenosis.

An early diagnosis and prompt treatment will improve the outlook for people with Gaucher’s.

Research published in the American Journal of Hematology suggests that the average life expectancy of a person with type 1 Gaucher’s disease is 68 years, compared with 77 years in the rest of the population.

Most patients with type 2 Gaucher’s disease will not survive beyond the first 2 years of life.

The National Gaucher Foundation says that life expectancy for type 3 Gaucher’s disease is shorter, but people with mild cases who receive treatment can live into their 50s.

Researchers hope that as they discover more about the disease, new treatments may improve the outlook for people with all forms of the disease.