Monitoring and Testing Gauchers Disease

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Dr Atul Mehta runs the Gauchers Centre at the Royal Free Hospital in London together with Specialist Nurse Linda Richfield. Dr Mehta explained the need for the regular monitoring and testing of patients.

Dr Mehta looks after 55 adult patients who receive enzyme replacement therapy at the Royal Free Hospital in London. All have Type 1 Gauchers disease. Twenty nine are male and 26 female. Twelve have the N370S/N370S mutation and 13 have the N370S/84GG mutations. One sufferer from Sri-Lanka has the R463C/R463C mutations.

Clinical History and Examination

'It is important to carry out a full clinical assessment reviewing symptoms, weight, appetite and quality of life parameters including mobility,' stressed Dr Mehta. 'Bruising, signs of anaemia, size of liver and spleen should also be assessed and organ function tests taken. These should be included in a severity scoring index.

Blood Tests

'Blood tests should include the following indicators that allow the degree of Gauchers disease to be assessed:

Ferritin level
Vitamin D and other markers of bone
Serum angiotensin converting enzyme and acid phosphatase
Chitotriosidase: this is an enzyme which originates from the Gaucher cells. It is extremely high in most patients but drops significantly during treatment with enzyme replacement therapy. Normal scale is up to 150 but in some patients with Gauchers disease it is as high as 30,000. Some individuals are unable to make chitotriosidase at all because of a genetic change and about one in five normal people are carriers of this genetic change and can only make chitotriosidase half as well as normal. A technique has been developed at the Royal Free Hospital whereby knowledge of this genetic change is used to improve the accuracy of chitotriosidase measurement and patient assessment.

Imaging

'Imaging different parts of the body and bones is valuable and should include:

DEXA Scanning This is carried out in the Medical Physics Department and uses a special camera to look at bone density in the spine and typically also in the hips. It is widely used to assess risk of fracture in osteoporosis but is also helpful in Gauchers disease
Magnetic Resonance Imaging (MRI) This technique allows doctors to accurately visualise the skeleton and demonstrates areas of damage. It is also a good way to assess the bone marrow which is replaced to a variable degree by Gaucher cells. MRI scans soft tissues and can be used to assess liver and spleen size. By performing these scans over time and comparing them, a good picture can be build up of the effectiveness of treatment.
Xray and Computerised Tomographic (CT) Scanning are older techniques which are nevertheless still useful.

Rarer Manifestations

'Disease in other organs is also recognised and this can include:
Liver disease which can proceed to cirrhosis
Lung complications which can cause shortness of breath, asthma and pulmonary hypertension
Cardiac changes including abnormalities of the valves
Kidney changes including kidney failure
Parkinson's disease-like symptoms
Blood diseases which can rarely include cancers such as leukaemia, lymphoma and myeloma
Complications in pregnancy

'Unfortunately there are many unans-wered questions regarding the precise causes of these complications and their relationship to Gauchers disease.

'A further important aim in monitoring patients is to make sure there are no adverse events from the enzyme therapy although fortunately this appears to be uncommon. Some patients do make antibodies to the enzyme but this does not seem to affect the effectiveness of the treatment.'

Future Challenges

Dr Mehta said that bone disease remains a problem for many sufferers of Gauchers disease. In addition there are other challenges to face:

Co-ordination of funding to manage the advent of more patients so that patients will not have to wait unnecessarily to begin treatment
Development of diagnostic centres in the UK for rare diseases. There is a need to retain expertise in similar diseases such as Gauchers disease and other lysosomal disorders
Development of a national programme so that Centres can work even closer together and develop further guidelines
Recruitment of young physicians to work in this field.
Further the partnership between doctors and patients and their support groups
Quality control: Government must know what doctors are doing and there must be a willingness to be open and to be inspected.

Dr Mehta said he and Specialist Nurse Linda Richfield held regular meeting with the hospital administrators regarding patients. There is a need to update health authorities and the National Specialist Commissioning Advisory Group at the Dept of Health who fund the four Centres.

Monitoring

Dr Mehta summarised his talk asking and answering the following questions regarding monitoring:

Who? Patients and carers
By whom? Doctors and their team
What? Condition, treatment and funding arrangements
Why? To improve health and make treatment more effective
How? By doing blood tests and imaging
Where? In the hospital but increasingly over the telephone
When? Every six months.

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