Long-term experience in diagnosis and treatment of Gaucher disease in Croatia
Gaucher disease is the most common lysosomal storage disorder with the incidence of around 1:40-60 000 inhabitants. Accordingly, it can be assumed that there are 20-30 patients with Gaucher disease in Croatia today. The cause of this storage disorder is an autosomal recessive inherited glucocerebrosidase deficiency, which results in decreased breakdown of sphingolipids. The severity of the disease depends on the residual activity of the enzyme, and the changes affect almost all human organs, mostly liver, spleen, bones, lungs and brain. Gaucher disease is extremely serious, disabling, and potentially fatal unless the treatment is started in time. There are three types of the disease. Type I, or so-called “non-neuropathic” form, is the most common type in Europe, while the neuropathic forms (types II and III) are less frequent (5-10%). Types II and III are characterized by the central nervous system involvement and are usually diagnosed in childhood. The diagnosis is easy to establish by measuring enzyme glucocerebrozidase activity in leukocytes or fibroblasts. Disease activity can be predicted by the serum level of chitotriosidase. Enzyme replacement therapy with imiglucerase (Cerezyme®) is a gold standard today. Imiglucerase prevents progression of disease and patients can have normal life. So far, 13 adults and 2 children have been diagnosed with Gaucher disease in Croatia. Eleven of 13 adult patients and both children take imiglucerase, which has decreased their spleen and liver size and number of bone pain crises and normalized their platelet and erythrocyte count. However, imiglucerase does not revert bone changes, e.g. avascular hip necrosis or collapse of the vertebra, but it does prevent further bone deterioration. Thus, treatment with imiglucerase should be started immediately after establishing diagnosis to prevent irreversible changes in different organs. More recently, an enzyme inhibitor that decreases the production of the substrate (miglustat) has been introduced. Chemical chaperone therapy and gene therapy hold promise for the future
Key words:
drug therapy; Gaucher disease; imiglucerase; lysosomal storage diseases, nervous system
