What We Can Achieve With Treatment

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At the Gauchers Association's 6th Conference held in Manchester on 30 November 2004, Prof Timothy Cox described what can be achieved with treatment for people with Gaucher disease.


The symptoms of Gaucher Disease are what the patient feels: tiredness, fever, general malaise, bleeding, abdominal swelling, bone pain, impaired growth and so on. The signs of the disease are those discovered by examination: low platelets, enlarged liver and spleen and skeletal abnormalities among others. In the assessment of a condition and its response to treatment, clearly a patient's quality of life is important and determined by their physical, mental and social well being - health is not merely the absence of disease.


The extent to which an improved health-related quality of life can be achieved is governed by what is deliverable and what might be delivered in the future. The aims are to abolish symptoms, cure the disease in all the tissues and organs and prevent complications - all with the minimum of discomfort and risk - and conveniently.

Specifically, the main aims of treatment in Gaucher Disease are divided up as follows:

Blood and Spleen: to avoid anaemia, low white cell and platelet counts, spleen enlargement, risk of rupture and scarring when the blood supply is stopped.

Liver: to avoid enlargement and scarring (cirrhosis, portal hypertension, liver failure). Bones: to avoid pain, fractures, joint replacements, and lytic lesions (local erosion of bone).

Other organs: to prevent lung infiltration and other rare long-term complications, for instance pulmonary hypertension and neuronopathic disease.

Risks of infection: to prevent infection, (especially if patients have had their spleen removed in the period before enzyme therapy was introduced).

Enzyme Replacement Therapy

The first patient who we treated with enzyme replacement therapy, in those days Ceredase, was blood-transfusion dependent: his blood counts were low. His spleen had also been removed in the past and he had pain in his ankles which stopped him walking. A bone marrow transplantation was considered but fortunately enzyme replacement therapy had just become available and he improved dramatically after receiving it. He could walk again and drive a car.

Evidence from pooled international registry data has shown that after five years of enzyme replacement therapy nearly all patients can expect their blood counts to improve, spleen and liver volume to decrease and a reduction in bone pain. Symptoms and signs of Gaucher Disease improve. These and other studies amassed over more than a decade of experience indicate that there are clear deliverables from enzyme replacement therapy.


Features Unlikely to be Reversed

Clearly some established features of the disease, which arise before treatment starts, are unlikely to be reversed especially at sites where scarring has occurred. Other features include:

Outcomes of Therapy

The outcome of enzyme replacement therapy depends on the extent of pre-existing disease, the availability of therapy, disease activity and compliance (continuing regular treatment).

Future Prospects

The success of enzyme replacement therapy depends on early detection of disease, early therapy for all and compliance. This is partly dependent on making a swift and correct diagnosis aided by valid laboratory tests. The tests are easy - it is suspecting the diagnosis and searching for it that is the special challenge.

When a patient complains about discomfort in the abdomen, the spleen needs to be felt. If a hip is giving pain, the patient needs to be referred for specialist advice.

There needs to be heightened awareness of which diseases can cause these problems and great persistence to discover the cause is often needed by both clinician and patient. Clearly it is particularly important to identify those conditions which are readily treated, such as Gaucher Disease.

Compliance is medical jargon which means the acceptability (and accep-tance) of treatments recommended by doctors - in the case of enzyme re-placement therapy, infusing prescribed medication regularly as indicated by the treating physician.

We have had three patients who stopped enzyme replacement therapy for different reasons but against our advice.

One, who has mild disease and the mutations N370S/N370S stopped for two years. Her chitotriosidase (a biochemical marker) remained stable and her spleen stayed the same size. However the other two patients deteriorated rapidly with one pre-senting with a bilateral hip necrosis after one year. Both these patients had recurrence of their symptoms. The reasons for their withdrawal from therapy were personal. I hope that it will be possible to start all back on treatment soon.

Bone Research Study

It is very good to be able to announce that the bone research study is underway. It is being conducted by the four national Gauchers centres and is funded by the Gauchers Association.

There will be three phases; the first phase is to study the bone manifestations in children and adults in the UK. A bone specific inventory and analysis will be undertaken, organized by my colleague Dr Patrick Deegan and Research Nurse, Jane Tindell. Both are based in Cambridge and will work on this project which is shared with all the Centres.

The outcome will act as an invaluable repository for future analytical research. The study will address key aspects of bone disease and will facilitate a systematic analysis of the blood factors involved in its manifestations to be carried out in phases 2 and 3 of the project. By identifying changes associated with some aspects of the skeletal injury, new pathways for treatment and risk management are expected to emerge.

The research will also add value to new clinical practice showing what measurements should be highlighted for special attention - a matter already examined by Dr Ashok Vellodi and Dr Ed Wraith in the case of children with Gaucher disease. Phases 2 and 3 will be completed during the last 18 months of the three year study .

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Source: Gauchers News March 2004.
© Copyright Gauchers Association 2004.