In:
Journal of Inherited Metabolic Disease, Wiley, Vol. 28, No. 1 ( 2005-01), p. 21-33
Abstract:
Anderson‐Fabry disease (referred to as Fabry disease) is an X‐linked disorder characterized by a deficiency of the lysosomal enzyme α ‐galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb 3 ), the main substrate of the defective enzyme. Enzyme replacement therapy (ERT) offers a specific treatment for patients with Fabry disease, though monitoring of treatment is hampered by a lack of surrogate markers of response. In this study, the efficacy of long‐term ERT in six Fabry hemizygotes and two symptomatic heterozygotes has been evaluated. Patients were administered recombinant α ‐galactosidase A every 2 weeks for up to a year. The efficacy of ERT was assessed by monitoring symptomatology and renal function. Urinary glycolipid concentration was estimated by a novel tandem mass spectrometric method. Urine glycolipid (Gb 3 ) was elevated at baseline and fell impressively on ERT where patients were hemizygotes and in the absence of renal transplantation. In heterozygotes and in a recipient of a renal allograft, elevations and changes in urine glycolipids were less pronounced. In one patient, after several months of ERT, there was a transient increase in Gb 3 concentrations to baseline (pre‐ERT) levels, associated with the presence of antibodies to the recombinant α ‐galactosidase A. The marked decline in urine Gb 3 on ERT, and its subsequent increase in association with an inhibitory antibody response, suggest that this analyte deserves further investigation as a potential marker of disease severity and response to treatment.
Type of Medium:
Online Resource
ISSN:
0141-8955
,
1573-2665
DOI:
10.1007/s10545-005-4415-x
Language:
English
Publisher:
Wiley
Publication Date:
2005
detail.hit.zdb_id:
2006875-X
