Gaucher disease is a rare inherited metabolic disorder that results in the abnormal accumulation of certain types of lipids (fatty substances) in the spleen, bone marrow, liver, and lungs, and sometimes in the brain. People with Gaucher disease have a problem with the enzyme glucocerebrosidase, which is either not made in the first place, or more commonly is not very efficient. When this enzyme functions normally it breaks down a glycolipid called glucosylceramide, and when this doesn’t happen – as in Gaucher disease – the lipid is not digested and is simply stored in the lysosomes.

Enlargement of the spleen and liver are the most characteristic symptoms of Gaucher disease. Damage to the spleen and liver can cause a number of hematological complications, including decrease in the number of red and white blood cells and platelets. Gaucher disease affects bone quality, leaving patients vulnerable to fractures which can occur after low impacts that would not damage the bone in a person without the disease.

SUBTYPES OF GAUCHER DISEASE

Gaucher disease has been traditionally classified into three subtypes, depending on the symptoms and the timing of their development.

Type 1 Gaucher disease is the most common form of the disease. The mutation is most frequent in the Ashkenazi Jewish people. Type 1 Gaucher disease is also referred to as the adult or non-neuropathic form of Gaucher disease, in which the brain is not affected. People with type 1 Gaucher disease have an enlarged spleen and liver, anemia and a low platelet count, and may also experience bone pain and bone deterioration. Symptoms can appear at any age.

Type 2 Gaucher disease (infantile or acute neuronopathic) occurs rarely and shows no particular ethnic predisposition. Type 2 is the most severe form of Gaucher disease, with onset within the first 6 months of life, and a maximum life expectancy of about 2 years. Apart from splenic and liver enlargement, infants with type 2 Gaucher disease suffer extensive and progressive brain damage.

Type 3 Gaucher disease is common in the population of the Norbotten region of Sweden. It is also referred as juvenile or chronic neuronopathic Gaucher disease, because the neurological symptoms appear in early to late childhood. The neurological accumulation is often seen initially in children as problems with moving the eyes correctly, learning difficulties at school, or auditory problems, and may eventually lead to difficulty with movement and balance.

Recently, new clinical information have shown that type 1 Gaucher disease patients may also have some degree of neurological signs and symptoms, suggesting a continuum between neurologic and non-neurologic forms of Gaucher disease.

WHO CAN GET GAUCHER DISEASE?

Gaucher disease is a genetic disorder inherited as an autosomal recessive trait, which means that it can occur with equal frequency in both males and females, and both parents must carry the mutation for the child to have the disease. If both parents are carriers, then there is a 1 in 4 chance that the child will have Gaucher disease, a 1 in 2 chance that the child will not have the disease but will be a carrier, and a 1 in 4 chance that the child will neither have the disease nor be a carrier.

HOW IS GAUCHER DISEASE DIAGNOSED?

  • The simplest way to diagnose Gaucher disease is to measure levels of the enzyme glucocerebrosidase in the blood.
  • Genetic carrier status: people with Gaucher disease, or those who have a family history of Gaucher disease, may be tested for the genes linked to the condition.

HOW CAN TYPE 1 GAUCHER DISEASE BE TREATED?

It is possible to treat type 1 Gaucher disease. Treatment options are governed by the severity and rate of disease progression, which is highly variable from one individual to another. There are no approved treatments for type 2 or type 3 Gaucher disease.

Therapeutic options

In patients with Gaucher disease, there is excessive accumulation of the substrate glucosylceramide, because the enzyme glucocerebrosidase is either reduced in quantity or not present at all. It is possible to restore the balance by either increasing the amount of enzyme or reducing the amount of substrate.

Enzyme replacement therapy

Enzyme replacement therapy (ERT) was the first therapy to be introduced for Gaucher disease in 1991. The deficient enzyme is given to the patient by intravenous perfusion (usually every 2 weeks), and breaks down the built up substrate, glucosylceramide.

Substrate reduction therapy

Substrate reduction therapy (SRT) involves the oral administration of a small molecule drug that inhibits the first step in the formation of the substrate glucosylceramide. As a result, cells have less glucosylceramide needing to be broken down, and even though the deficiency in the glucocerebrosidase enzyme remains, it is able to keep up with the small amounts of glucosylceramide produced in the cells, and also to break down glucosylceramide that is already stored.

Bone marrow transplantation

Bone marrow transplantation is another therapeutic option to replace damaged blood forming cells. Although this treatment can be helpful in Gaucher disease patients, it is not considered to be an ideal option due to the high morbidity and mortality risk and limited effectiveness.

Please consult your physician or pharmacist for further information.

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