Last update:
06-Jul-2004

OBJECTIVE The biochemical and molecular investigation of Gaucher disease in Greece.

METHOD Clinically suspect cases over 20 years from all over Greece were studied. The biochemical investigations included assays of chitotriosidase in plasma and of β-glucosidase in white blood cells and/or skin fibroblast cultures. Patients were systematically investigated for the presence of the mutations N370S, D409H, L444P, R463C and IVS10^-1GA using PCR followed by restriction enzyme studies.

RESULTS During the last 20 years, a total of 67 patients with type I (n=55), II (n=8), III (n=4) of Gaucher disease were diagnosed. White blood cell βglucosidase activity was diagnostic for the majority of patients but there was overlap between affected individuals and carriers, as well as between carriers and normal individuals. Fibroblast β-glucosidase levels clearly differentiated between the above groups. However there was no correlation between β-glucosidase residual activity and the type of disorder. Plasma chitotriosidase levels were elevated only in Gaucher patients. Four mutations, N370S, D409H, L444P, IVS10^-1 GA were identified.

CONCLUSIONS Gaucher disease is the most frequent lysosomal storage disease in Greece. It accounts for 31.3% of all cases diagnosed with a lysosomal storage disease in this laboratory in the last twenty years. Assaying of β-glucosidase in white blood cells and/or fibroblasts establishes the diagnosis of the disorder. Fibroblast assay is strongly recommended for individuals with high white blood cell β-glucosidase residual activity. Elevation of plasma chitotriosidase levels is an excellent pathognomonic criterion. Four mutations cover 80.8% of the alleles of this group of patients.

Key words: β-glucosidase, Chitotriosidase, Gaucher disease, Lysosomal storage diseases.