- What is Gaucher Disease?
- Risk Factors
- Clinical Examination
- How is it Diagnosed
What is Gaucher Disease?
There are three subtypes of Gaucher disease:
- Type 1 Gaucher disease is the most common form, and is the least serious.
- Type 2 Gaucher disease is rare, and fatal in the early stages of life.
- Type 3 Gaucher disease is an intermediate form between types 1 and 2.
Type 1 Gaucher disease is also known as non-neuronopathic GD, whilst type 2 and type 3 Gaucher disease are commonly classified as neuronopathic GD. Non-neuronopathic GD (type 1 GD) can be acute or subacute. Neuronopathic GD can be subclassified on the basis of central nervous system involvement.
The estimated wordwide prevalence of Gaucher disease is 1 per 40,000 to 1 per 75,000 births. In Australia, the prevalence is estimated at 1 in 57,000 live births.
Type 1 Gaucher disease makes up approximately 90% of cases of Gaucher disease in Australia, and has an increased prevalence amongst Ashkenazi Jewish populations.
In contrast, types 2 and 3 are rare and affect only 1 in 100,000 to 1 in 150,000 births.
Gaucher disease is a genetically inherited autosomal recessive disorder. To pass it on to a child, both parents need to be either affected by Gaucher disease or by asymptomatic carriers of the disease.
Gaucher disease is known to have a higher prevalence amongst certain cultural and religious groups, including Ashkenazi Jews, and a number of non-Jewish European populations, including Northern Sweden.
The progression of Gaucher disease is heavily dependent upon the subtype of the disease that an individual inherits, as well as the age of onset of the disease.
Type 1 Gaucher disease
In general terms, type 1 Gaucher disease appears in adulthood and has a slow and indolent progression. Many individuals are able to live a full life using only symptomatic relief for their symptoms. However, if type 1 Gaucher disease manifests early in life, progression of the disease tends to be more abrupt, and more extensive treatment is usually required.
Type 2 Gaucher disease
Type 2 Gaucher disease usually manifests before 2 years of age and is universally fatal within 2 years.
Type 3 Gaucher disease
Type 3 Gaucher disease has the most varied course and outcomes, with a life expectancy of 20–40 years. In terms of symptoms and progression, it lies in between type 1 and type 2 Gaucher disease. It has an earlier onset and a more pronounced progression than type 1.
Three subtypes of type 3 Gaucher disease have been classified:
- Type 3a: Found in Northern Sweden, typically showing symptoms of early dementia.
- Type 3b: Predominantly bone, liver and spleen involvement with some neurological symptoms.
- Type 3c: Rare, with cardiovascular and neurological symptoms.
Gaucher disease has a widespread effect on the body, including the enlargement of the liver and spleen which may or may not be symptomatic. This can appear as early satiety, abdominal bloating or discomfort, weight gain or increase in abdominal girth.
Gaucher disease can cause bone pain, fatigue due to anaemia, recurrent bleeding disorders (e.g. nose bleeds, heavy periods), painful and enlarged lymph nodes, and recurrent fractures. Affected individuals may also feel tired and generally unwell.
In type 3 Gaucher disease, there may be neurological symptoms affecting vision and cognition.
A thorough clinical examination is required if a medical practitioner is exploring the possibility of Gaucher disease. This includes an abdominal examination to look for an enlarged liver or spleen, a cardiorespiratory examination to look for signs in the lungs, and an examination of lymph nodes. Blood tests should also be performed to investigate fatigue and easy bleeding and bruising.
If neurological involvement is suspected, a specialist eye and neurological assessment will also be required.
How is it Diagnosed
The definitive method of diagnosing Gaucher disease is by performing a blood test to look at the levels of the defective enzyme.
A number of methods can provide useful information, including:
- Positive clinical examination findings;
- Laboratory investigations (e.g. blood tests, biochemical markers, genotyping and DNA analysis);
- Specialised MRI scans; and
- Bone marrow biopsy if required.
Individuals with type 1 Gaucher disease are usually able to live a normal lifespan. Recent evidence suggests that individuals with type 1 Gaucher disease may, on average, have a life expectency nine years less than the normal population.
Type 2 Gaucher disease is universally fatal within two years.
Type 3 Gaucher disease has a life expectancy of 20 to 40 years. However, recent advances in medical therapy are likely to extend the length and quality of life of individuals with type 3 Gaucher disease.
Treatments for Gaucher disease include symptomatic relief, enzyme replacement therapy (ERT), substrate reduction therapy (SRT) and bone marrow transplantation.
In the event that adult patients with type 1 Gaucher disease are only mildly affected, symptomatic relief (e.g. pain control, blood transfusions, and treatment of infective exacerbations) may be all that is required. Careful and regular monitoring should be conducted to ensure that irreversible complications do not result from the disease.
Enzyme replacement therapy (ERT)
Enzyme replacement therapy is the current standard of care treatment for moderately to severely affected individuals with Gaucher disease. It aims to supplement the low levels of enzymes that are needed to break down the fat deposits caused by Gaucher disease.
The approved drug for this purpose is Cerezyme (imiglucerase). It is very expensive, so its use is restricted to symptomatic children and adults with moderate to severe disease. Cerezyme is funded by the Australian government under the Life Saving Drugs Program for people who meet specific criteria.
Individuals who are undergoing enzyme replacement therapy are required to have routine examinations, including an annual MRI scan, to monitor their treatment.
Substrate reduction therapy (SRT)
For individuals who cannot receive ERT because of treatment failure or unsuitability, an alternative medication is available that aims to reduce the production of fats that are deposited in organs around the body. This medication is called Zavesca (miglustat). It is not yet funded by the PBS or the Life Saving Drugs Program.
Bone marrow transplantation
Bone marrow transplantation is rarely used now, because complications were high and alternative treatments with ERT and SRT have proven to be just as effective.
Gene therapy is a novel approach to treating Gaucher disease. It uses a virus to deliver the missing genes to blood stem cells. This method of treatment has only been trialled in mice and is yet to be proven in humans.
Genetic testing is an important consideration if Gaucher disease is a concern, or if individuals are aware of the disorder occurring in their family. Testing can be arranged to assess for the presence of genetic mutations which may lead to Gaucher disease in the tested individual. Testing can determine if an individual is a carrier of the disease and therefore estimate the risk of passing the disorder on to children.
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