Marked variation in blood beta-hexosaminidase in Gaucher disease.
ABSTRACT Gaucher disease is due to a primary deficiency of acid beta-glucosidase activity and is associated with secondary elevations of several plasma/serum lysosomal enzyme activities, including beta-hexosaminidase. We analyzed plasma and serum beta-hexosaminidase A & B activities in 55 patients with enzyme-documented Gaucher disease. The mean beta-hexosaminidase activity was increased and the percent of the A isozyme decreased, consistent with earlier studies. Gaucher disease patients had 2,067 +/- 1,491 nmol ml-1 h-1 units of beta-hexosaminidase activity with 51.9 +/- 15.5% beta-hexosaminidase A compared to 1,086 +/- 260 nmol ml-1 h-1 and 67.8 +/- 4.0% beta-hexosaminidase A in normal controls and 965 +/- 261 nmol ml-1 h-1 and 43.6 +/- 5.5% beta-hexosaminidase A in Tay-Sachs disease heterozygotes. Contrary to previous reports, marked heterogeneity of both total plasma/serum enzyme activity and isozyme pattern was noted, as some patients had normal enzyme levels and others had severe reductions in the percent of hexosaminidase A. These data argue against the suggestions of recent studies that routine serum beta-hexosaminidase testing done in Tay-Sachs disease heterozygote detection programs can be effectively used to screen for patients with Gaucher disease.
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ABSTRACT: An overview of the most important plasma abnormalities that can be found in Gaucher's disease is presented in this chapter. Attention is focussed on their practical applications and possible clinical relevance. In addition, the result of studies on metabolic alterations in Gaucher's disease are reviewed.Baillière s Clinical Haematology 12/1997; 10(4):691-709. DOI:10.1016/S0950-3536(97)80034-0
Article: Gaucher disease.Medicine 12/1995; 74(6):305-23. DOI:10.1097/00005792-199511000-00002 · 4.87 Impact Factor
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ABSTRACT: To assess the discriminating power of multiple cerebrospinal fluid (CSF) biomarkers for Parkinson's disease (PD), we measured several proteins playing an important role in the disease pathogenesis. The activities of beta-glucocerebrosidase and other lysosomal enzymes, together with total and oligomeric alpha-synuclein, and total and phosphorylated tau, were thus assessed in CSF of 71 PD patients and compared to 45 neurological controls. Activities of beta-glucocerebrosidase, beta-mannosidase, beta-hexosaminidase, and beta-galactosidase were measured with established enzymatic assays, while alpha-synuclein and tau biomarkers were evaluated with immunoassays. A subset of PD patients (n=44) was also screened for mutations in the beta-glucocerebrosidase-encoding gene (GBA1). In the PD group, beta-glucocerebrosidase activity was reduced (P < 0.05) and patients at earlier stages showed lower enzymatic activity (P < 0.05); conversely, beta-hexosaminidase activity was significantly increased (P < 0.05). Eight PD patients (18%) presented GBA1 sequence variations; 3 of them were heterozygous for the N370S mutation. Levels of total alpha-synuclein were significantly reduced (P < 0.05) in PD, in contrast to increased levels of alpha-synuclein oligomers, with a higher oligomeric/total alpha-synuclein ratio in PD patients when compared with controls (P < 0.001). A combination of beta-glucocerebrosidase activity, oligomeric/total alpha-synuclein ratio, and age gave the best performance in discriminating PD from neurological controls (sensitivity 82%; specificity 71%, area under the receiver operating characteristic curve=0.87). These results demonstrate the possibility of detecting lysosomal dysfunction in CSF and further support the need to combine different biomarkers for improving the diagnostic accuracy of PD. (C) 2014 International Parkinson and Movement Disorder SocietyMovement Disorders 07/2014; 29(8). DOI:10.1002/mds.25772 · 5.63 Impact Factor