12 A practical approach to diagnosis and management of Gaucher's disease

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The diagnosis of Gaucher's disease is established by demonstration of reduced acid β-glucosidase activity in peripheral blood leukocytes. Genotyping at the glucocerebrosidase gene locus can give additional prognostic information and facilitate carrier detection. However, extreme phenotypic diversity precludes reliable prediction of prognosis in individual patients. Histological diagnosis of Gaucher's disease is unnecessary and can be misleading. A range of clinical, radiological and laboratory parameters are useful for staging disease activity which is central to achieving optimal timing to initiate enzyme therapy. Treatment should be individualized to obtain maximum therapeutic response. The recent introduction of chitotriosidase measurements has provided a valuable indicator of total cellular burden of storage cells. Serial measurements of chitotriosidase activity are useful for monitoring disease progression as well as response to therapy. A number of adjuvant therapies are available for use in conjunction with enzyme treatment. Special considerations apply to management of affected children.

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      For example, in the initial chitotriosidase study, plasma activity was found to be elevated on average 641-fold (median control plasma, 20 nmol/mL/h; range, 4-76 nmol/mL/h; median Gaucher plasma, 12 824 nmol/mL/h; range, 3122-65 349 nmol/mL/h).5 Plasma chitotriosidase has proven to be a useful surrogate marker for Gaucher disease manifestations and is used for diagnosis, early determination of onset of disease, and monitoring of therapeutic efficacy.5-8 Plasma chitotriosidase levels do not reflect one particular clinical symptom, but rather are a reflection of the total body burden of Gaucher cells.9

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