Gauchers Disease: Good Housekeeping

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An open meeting about Gauchers disease, how it is inherited, what the symptoms are and how patients can be treated took place at the Royal Free Hospital, London on 27 March 2003. Dr Atul Mehta, Head of the Gauchers Centre and Consultant Haematologist gave a comprehensive talk about the condition.

'Gauchers disease is an inherited disease caused by the deficiency of a particular enzyme which is a type of protein', explained Dr Mehta. 'It is inherited in a recessive fashion - carriers are completely healthy and greatly outnumber sufferers, who are the people who develop symptoms of the disease. Even people who inherit the faulty gene from both parents may not show symptoms, even at a late age.

'Everyone inherits a gene from both parents for each protein their body makes. These genes form an information blueprint which encode (make) different proteins. The proteins fall into different categories: structural such as collagen to help form skin, functional eg haemoglobin which is present in red cells and helps to carry oxygen through the body, converters, eg enzymes such as insulin which helps to regulate the right amount of sugar in your body and regulators, eg oncogenes which keep the right balance of cells.

'Every human cell contains the full DNA code but not all genes are expressed (active) within the cells. Some are switched on and some are switched off. 'Scientists have been curious to discover whether being a carrier of this disease led to some advantage or survival benefit in the past, for instance to ward off tuberculosis or other infectious diseases. However nothing has as yet been discovered to prove this.'

Housekeeping Genes

Some genes are called housekeeping genes - these are switched on in all cells. Dr Mehta gave an example of a kitchen where the bulk of housekeeping services are carried out. There is a cooker and boiler to create heat and energy. Cupboards store food for energy. A washing machine cleans clothes and a waste disposal unit recycles food into waste.

He explained that certain cells in the body called macrophages have a similar function to a waste disposal unit as they break down old cells and recycle them. Macrophages in the spleen break down old blood cells. Blood cells are produced in their millions every second and the old ones need to be disposed off.

'Normally macrophages recycle the blood cells with the help of an enzyme called glucocerebrosidase. But in people with Gauchers disease there is insufficient enzyme so the old cells don't get broken up and material is stored in lysosomes within the macrophage. These cells become increasingly enlarged as they cannot break down the waste material and they accumulate in the spleen, liver, bone marrow and sometimes other parts of the body.

'Gauchers disease is the most common lysosomal storage disorder but there are 40 others.'

Symptoms and Signs

The symptoms of Gauchers disease are what patients feel; the signs are what is observed by the physician through clinical examination or laboratory tests. The first description given below is the symptom which is followed by the sign:


'Prior to 1990, treatment for patients with Gauchers disease was purely palliative, that is relieving or treating the symptoms as they occurred. Therefore, splenectomy (removal of the spleen), orthopaedic surgery (eg replacement of the hip or other joints) and pain relief drugs were the best way of easing the patient's condition.

'However in 1991, enzyme replace-ment therapy became available which targeted the macrophages and dealt with the underlying problem of re-moving the build up of waste material in the spleen, liver and bone marrow.

'Ceredase, and then the new recombinant DNA form of the drug called Cerezyme, has been an effective form of treatment although unfortunately damaged bone can rarely be made healthy again.

'Most of our patients at the Royal Free are receiving Cerezyme and most are self administering the therapy in their own homes. Home treatment is the preferred choice of our patients whose ages range from 17 to 92.

'Now a new oral drug called Zavesca has just received European approval which is for patients with mild to moderate Type 1 Gauchers disease for whom enzyme replacement is unsuitable. This is a small molecule drug which stops some of the waste material building up in the first place. Therefore there is less to store and break down and the idea is that the patient's own supply of enzyme is sufficient to cope with the remainder. Patients taking this drug will need to be closely monitored for side effects.

'An advantage of Zavesca, also known as substrate reduction therapy, may be that because it can cross the blood/brain barrier it may reduce the burden of neurological disease in Type 3 Gauchers disease. A trial for Type 3 patients is due to take place in the UK and America.

Raise Awareness

'One of the aims of this meeting is to raise awareness of Gauchers disease as I believe there are still undiagnosed individuals living within the catchment area of the Royal Free Hospital and beyond. There may also be sufferers who are unaware that there is now a treatment.

'Our Gauchers Centre is also part of a Research Project to look at the bone symptoms of the disease as there are still many unanswered questions. The Gauchers Association continues to raise funds for this important piece of research.

'The Royal Free Hospital is one of two Centres looking after adults with Gauchers disease. There are also two paediatric Centres. These are designated by the Department of Health. It is important that there is a national approach to rare diseases so that expertise can be concentrated to maximum benefit.

'Finally I would like to thank my nursing team: Specialist Nurses Linda Richfield, Sian Goodwin and newly arrived Alan Milligan.

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Source: Gauchers News October 2003.
© Copyright Gauchers Association Ltd 2003.