Lysosomal leukocyte beta-D-glucuronidase during enzyme replacement therapy in Fabry disease.
OBJECTIVE
Fabry disease results from a deficiency in the activity of alpha-d-galactosidase A and subsequent accumulation of neutral glycosphingolipids in lysosomes. This study investigated whether lysosomal enzymes can indicate biochemical changes in the lysosomal apparatus induced by enzyme replacement therapy (ERT).


METHODS
Eight patients were monitored by clinical and biochemical tests and several lysosomal glycohydrolases were measured in plasma and leucocytes.


RESULTS
Before starting ERT, beta-d-glucuronidase in leukocytes was markedly increased. After 1 month of therapy, enzyme levels dropped in all patients. In the patients who regularly followed the therapy, the enzyme levels remained stable for the next 20 months. In one patient who interrupted therapy for 2 months, the enzyme levels rose again.


CONCLUSIONS
Lysosomal enzymes can be useful for monitoring biochemical changes in patients with Fabry disease receiving ERT. Though these findings refer to only a small number of patients, the correlation between beta-d-glucuronidase levels and ERT is interesting and might serve as a basis for further studies to define the potential of this enzyme in monitoring the effects of ERT in lysosomal storage disorders.
Goi
Giancarlo
G
Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Via Saldini, 50, 20133 Milan, Italy. giancarlo.goi@inimi.it
Massaccesi
Luca
L
Burlina
Alessandro P
AP
Baquero Herrera
Claudia J
CJ
Lombardo
Adriana
A
Tettamanti
Guido
G
Burlina
Alberto B
AB
D000328:Adult; D000704:Analysis of Variance; D003592:Cytophotometry; D000795:Fabry Disease / Q000188:drug therapy / Q000201:enzymology*; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000097:blood; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D000519:alpha-Galactosidase / Q000627:therapeutic use
D006026:Glycoside Hydrolases; D000519:alpha-Galactosidase; D005966:Glucuronidase