What is Gaucher Disease?
Gaucher is a genetic lipid storage disorder, in which lipids (fatty
substances) build up in certain cells in the body (called macrophages). It
is caused by a missing or deficient enzyme called ‘glucocerebrosidase’,
which normally breaks down these lipids. Accumulation of lipids in cells in
the liver, spleen and bones can interfere with some of the normal processes
of the body.
Gaucher belongs to a group of conditions called Iysosomal storage disorders
(LSDs). There are 3 main types of Gaucher disease:
- Type 1 (Non-neuronopathic) – the most common type with variable symptoms
- Type 2 (Acute neuronopathic) – an acute, severe form affecting the
central nervous system in babies and infants
- Type 3 (Chronic neuronopathic) – a chronic form affecting the central
nervous system, that progresses over time
What are the signs and symptoms of Gaucher Disease?
Gaucher is different for everyone, with symptoms varying considerably from
person to person. Some people experience severe symptoms in childhood, while
some people have no symptoms or only mild symptoms and are diagnosed later
The most common clinical symptoms of Type 1 Gaucher are:
- Bone pain
- Tendency to bruise
- Enlarged liver
- Enlarged spleen
In Type 3 Gaucher, the nervous system is also affected and additional
- Abnormal eye movements
- Loss of muscle coordination
- Learning difficulties
What are the causes of Gaucher Disease?
Gaucher disease results from abnormal deposits of a fatty substance, known
as glucocerebroside or glucosylceramide. Normally, glucocerebrosidase is
metabolised (broken down) by an enzyme called glucocerebrosidase (acid β-glucosylceramidase).
In people with Gaucher disease, the gene that would normally tell the body
to produce this enzyme is altered (often called a gene mutation). This
alteration means that the enzyme does not work properly or is completely
absent. This in turn leads to a build-up of glucocerebroside in cells. It is
because of this build-up that Gaucher disease is referred to as a storage
disorder, and because the build-up happens in a part of the cell called the
lysosome it is called a lysosomal storage disorder (also known as lysosomal
Who is likely to be at risk of Gaucher Disease?
Gaucher is a rare genetic disorder affecting around 1 in 100,000 of the
population. Most people (over 90%) have Type 1 Gaucher. It affects males and
females equally. Gaucher is more common within the Ashkenazi Jewish
population, with approximately 1 in 1000 having Type 1 Gaucher.
Gaucher is an inherited disorder that is said to be ‘recessive’. This means
that a child needs to inherit a copy of the faulty gene from both parents to
How is Gaucher Disease diagnosed?
Patients who present with the above signs and symptoms may have the diagnosis
confirmed by the following methods;
The most reliable method of diagnosing Gaucher disease is to test the activity
of the glucocerebrosidase enzyme. This is carried out using a fluorometric assay
with the substrate 4-methylumbelliferyl-ß-D-glucopyranoside. In affected
individuals, glucocerebrosidase enzyme activity in peripheral blood leukocytes
is 0-15% of normal activity.
DNA testing may be carried out to identify the mutation of the Gaucher gene.
More than 200 different mutant GBA alleles have been identified in patients with
Gaucher disease. Some genotypes have been associated with different disease
characteristics. For example, patients with type 1 Gaucher disease who are
homozygous for the N370S mutation tend to have a later onset and a milder form
of the disease.
Histological tests, such as bone marrow aspirates and liver biopsies, may help
to diagnose identify Gaucher cells, but they should not be used as a first-line
diagnostic tool, as enzyme testing is more specific and other patients may
exhibit pseudo-Gaucher cells.
What are the treatments for Gaucher Disease?
Treatment of Gaucher disease consists of two components; symptom management and
replacement of the deficient or dysfunctional enzyme with enzyme replacement
therapy (ERT), or by use of Substrate Reduction Therapy (SRT, licensed for use
in patients unsuitable for ERT). Treatment needs to be tailored to the
individual. Because it is quite a rare condition, most people with Gaucher
disease are treated at specialist centres by doctors and nurses who are experts
in treating lysosomal storage disorders like Gaucher Disease. At these centres
the patient and their family can be assessed by a range of medical specialists
and advised on a specific treatment programme.