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In the last 18 months, Prof Ari Zimran and our team have published many research ideas that have evolved over the past decade in our Gaucher Clinic in Jerusalem, said Dr Debby Elstein after receiving the Alan Gordon Memorial Award, won jointly with her colleague Prof Zimran awarded at the UK Conference on 30 November 2003.
Our Gauchers Clinic in Jerusalem received its first grant for research into Gaucher disease more than 13 years ago from the Helen Manuel Foundation, a charity set up by the Association's chairman Jeremy Manuel in memory of his mother.
Since then, we have published many research ideas. We follow more than 500 patients at our Clinic. 493 patients have Type 1 Gaucher disease. Two children had Type 2. Four patients have Type 3b which is characterized by minimal neurological involvement but massive disease in their organs, and 12 patients have Type 3c, a unique variant seen in Japanese, Spanish and Arab families which is associated with a single genotype (genetic mutation) and is marked by progressive, life-threatening calcification of the left-heart valves so that they require replacement of these valves during their late teen years.
Today, 185 patients are receiving enzyme replacement therapy in Israel (one third of these children), and ten adults are receiving Zavesca, the oral substrate inhibitor that has recently gained European, American and Israeli marketing approval.
The advantage of having such a large group of patients in one clinic is that we can study many aspects of Gauchers disease, documenting both the most common associations and response to therapies, and also the more rare and uncommon features of this disease.
Enzyme Replacement Therapy
We have found that low-dose enzyme replacement therapy (15 units/kg body weight/every two weeks) is equally effective in reducing enlarged organs and improving haematological parameters of the disease, albeit at a slightly slower rate compared with higher and thus more costly regimens.
Enzyme therapy is especially beneficial in symptomatic children and, with early administration, prevents many of the more severe manifestations, including bone pains, as well as ensuring catch-up growth in height.
Weight gain is a dose-related side effect of enzyme therapy, in adults and children.
Research with our patients who have become pregnant during the last five years shows that they have done well including those who remained on enzyme therapy during the entire pregnancy. See Gauchers News October 2002 for full details.
Withdrawal from enzyme replacement therapy for periods of up to two years in some adult patients has shown no dramatic deterioration in disease-related symptoms and signs. However, although this may be considered for maintenance regimens in adults, it is not recommended for children.
Research by our orthopaedic surgeons, Dr Menachem Itzchaki and Udi Lebel, has shown that the clinical outcome and stability of prostheses (artificial joints) whether using cement or non-cemented methods are excellent and essentially no different than that reported in otherwise healthy persons undergoing hip replacements. (see Gauchers News October 2002).
Less Common Features
A Parkinsonian-like syndrome, initially reported by us, among a few very mildly affected patients with Type 1 Gaucher disease, has led to basic research by others into brain manifestations in Type 1 which has previously been classically defined as having no neurological or brain involvement.
Thus, today scientists are talking about a continuum of symptoms and signs for Gaucher disease rather than categorization according to Types 1, 2 and 3. Similarly, our involvement in the Zavesca clinical trials has underscored an earlier observation in our clinic that patients with Gaucher disease may have a defect in visuo-spatial cognitive function.
This however should be evaluated in the context of generally high intelligence among patients with Type 1 disease, some of whom have achieved international renown.
Infiltrative lung disease that is secondary to severe Gaucher disease may benefit from enzyme replacement therapy. On the other hand, we have reported pulmonary hypertension in some patients without any lung disease background, that began while on enzyme replacement therapy.
Although a relationship has been difficult to prove, withdrawal of enzyme treatment may be considered in these patients.
Routine echocardiographic monitoring is therefore highly recommended for all patients.
Calcification in D409H/D409H genotype
We have recently attempted to correlate genotypes (mutations) with specific clinical pictures, for example, the Arab patients with the D409H/D409H genotype who show no classic symptoms or signs other than abnormal eye movement but have calcification of the valves in the left side of the heart.
Enzyme replacement therapy given to two patients for nearly 10 years has resulted in no slackening of the calcification process and valve replacement was required. We have also researched the R496H mutation that seems to be associated with mild disease and like the N370S mutation protects against neurological involvement, whereas the V394L mutation, though apparently mild in a single copy, when associated with a severe mutation, does not protect against neurological involvement.
Generally no increase in cancer incidence
Studies from our large clinic population and in comparison with the data from the international Gaucher Registry, has shown no increase in cancer amongst patients with Gaucher disease other than the incidence of multiple myeloma (a blood cancer) which is higher.
Long term surveillance
It is important to continue long-term surveillance of patients, whether on various treatment regimens or not, to enable treating physicians to follow both gradual and sudden changes in the natural progression of their Gaucher disease and thereby help patients maintain optimum health and quality of life.
Gauchers News Contents
Source: Gauchers News March 2004.
© Copyright Gauchers Association 2004.