Gaucher disease Dr Trisha Macnair Gaucher disease is a rare genetic disorder, one of the most common of a group of conditions know as ’lipid storage diseases’; where abnormal amounts of fats (or lipids) are stored in certain cells in the body.

In this article

What causes it? Who's affected?

What are the symptoms? What's the treatment?

Screening

Gaucher disease is caused by a deficiency of an enzyme called glucocerebrosidase, which normally breaks down a fatty substance called glucocerebroside. This substance is constantly being produced by the body during the recycling of white and red blood cells, and in the brain during development and formation of the myelin sheaths around nerves. When it can’t be broken down properly, it accumulates within another type of cell called a macrophage, which usually has the job of removing bacteria and foreign bodies from the blood and tissues.

As a result of this accumulation, the affected macrophages (known as Gaucher cells) don’t function normally but gather in large amounts in the organs causing disruption to many body processes. The deficiency of the enzyme glucocerebrosidase is caused by an inherited mutation of the gene for acid beta-glucosidase or GBA. Gaucher disease is an autosomal recessive condition, which means that for a child to be affected it must inherit two copies of the abnormal gene, one from each parent.

There are several different types of GBA gene mutations, which means there are several different forms of Gaucher Disease. Traditionally, the condition has been divided into three main types:

• Type 1 Gaucher disease is the most common, and does not affect the central nervous system.
• In type 2 and 3 Gaucher disease, the nervous system is affected.

Some cases don’t fit exactly into these categories and there are a number of sub-types of the disorder. The severity of the disease can vary enormously. In type 1, some children develop severe complications early on while others live to old age without symptoms. It has been suggested that many people carry the mutation without knowing because they never develop significant symptoms

Gaucher disease may occur in people of any ethnic background, but type I is particularly common among people of Ashkenazi Jewish descent, nearly ten per cent may carry the gene, and up to one in 1,000 have the condition. The age at which Gaucher disease becomes apparent depends on the type severity of the disease.

Symptoms vary enormously from person to person and also depend on both the type of Gaucher disease, and the degree of enzyme deficiency (although even this measure can be a poor guide to severity).

Type I usually starts to cause problems in childhood with an enlarged liver and spleen, and low blood cell levels because the bone marrow (which makes blood cells) has been replaced by Gaucher cells. Anaemia, tiredness, easy bruising and a tendency to bleed are common. The bone itself may become thin and more likely to break and in some the lungs fill with abnormal macrophages, which interfere with breathing. Other features include growths of tissue in the conjunctiva of the eye and increased pigmentation of the skin. Most importantly there is no involvement of the nerves. Although there is a wide spectrum of severity, the disease usually progresses with time.

Children with type 2 usually appear normal at birth but symptoms develop within a few months and rapidly progress, with deterioration in the organs, enlargement of the liver and spleen, and damage to the nervous system causing problems such as abnormal eye movements, unsteadiness, swallowing problems and seizures. Growth stops, the child’s development regresses and few survive beyond the age of two.

In type 3 Gaucher disease (of which there are several sub-types) there is also damage to the nervous system but it’s later in onset and progresses more slowly.

There's no cure for Gaucher disease, although some researchers hope that one day gene therapy may provide the answer. In the past treatments have focused on controlling specific symptoms and reducing complications – for example removing the spleen (splenectomy) can help to control anaemia, and joint replacements can restore damaged joints. But other, more effective, treatments are now increasingly used.

Enzyme Replacement Therapy (ERT) given every two weeks, can alleviate symptoms that result from damage to most of the organs, with improvements in organ enlargement, anaemia, and bone damage and is now widely used in type 1 Gaucher disease.

Although it's difficult to get the replacement enzyme into brain tissue, ERT seems to have benefits in type 3 of the disease too, improving not just the general symptoms (and quality of life) but according to some research possibly even reversing, stabilizing or slowing the progression of the nervous system damage. However in those with established type 2 Gaucher Disease, ERT seems to have little effect on the progressive downhill course.

Other treatments which may be used in some cases include substrate reduction therapy, chemical chaperone therapy and bone marrow transplantation.

Gaucher disease is an inherited condition, where both parents carry the abnormal gene for the disease. When a baby inherits two copies of the faulty gene – one from each parent - they develop the condition.

The faulty gene has now been identified so it’s possible to test a person’s blood (especially if there is a family history of the condition or the person is from a high risk group) and tell them whether they carry the condition and could pass it on. But the problem remains in type 1 Gaucher disease that the severity of the disease ranges from no symptoms at all to severe illness, so it’s very difficult to predict just how badly a child will be affected.

It’s also possible to look at a person’s blood for levels of activity of the glucocerebrosidase enzyme, and low levels suggest the carrier or disease state. But once again, this indicator does not correlate well with how likely someone (or their offspring) is to develop symptoms of the disease, or how severe those symptoms will be.

Prenatal screening, to look for Gaucher disease, is also possible using amniocentesis or chorionic villus sampling (CVS) to check a child’s genetic status. If an unborn child is found to have the condition the parents must then choose whether to continue with the pregnancy, but in type 1 this decision must be made without any certainty as to how badly the child may be affected.

This article was last medically reviewed by Dr Trisha Macnair in December 2008.