12 A practical approach to diagnosis and management of Gaucher's disease PRAMOD K. MISTRY BSc, PhD, MBBS, MRCP Senior Lecturer and Honorary Consultant Physician Hepato-biliary and Liver Transplant Unit, Royal Free Hospital School of Medicine, Pond Street, London NW3 2QG, UK AYALA ABRAHAMOV MD Senior Lecturer in Paediatrics Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel The diagnosis of Gaucher's disease is established by demonstration of reduced acid [3- 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 chitotfiosidase 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, Key words: leukocyte acid [~-glucosidase, glucocerebrosidase mutations, mannose- terminated glucocerebrosidase, splenectomy. The diagnosis of non-neuronopathic Gaucher's disease should be con- sidered in any patient with unexplained splenomegaly with or without bleeding diathesis, skeletal manifestations and hepatomegaly. It should be high on the list of differential diagnosis in any child presenting with hepatosplenomegaly and neurological signs. Another indication for diagnostic investigations includes a positive family history of Gaucher's disease. Screening investigations are not recommended for asymptomatic individuals just because they have Jewish ancestry since a significant number of these individuals have mild disease that would never otherwise BailIikre ~ Clinical Haematology Vot. I0, No, 4, December 1997 ISBN 0-7020-2378-7 0950-3536/97/040817 + 22 $12,00/00 817 Copyright © 1997, by Bailli~re Tindall All rights of reproduction in any form reserved