Received on June 3, 2004
Accepted on August 10, 2004

Molecular Diagnostics and Genetics

Immunoquantification of -Galactosidase: Evaluation for the Diagnosis of Fabry Disease

¹ Lysosomal Diseases Research Unit, Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, SA, Australia, and Department of Paediatrics, University of Adelaide, Adelaide, SA, Australia.
² Lysosomal Diseases Research Unit, Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, SA, Australia.

^* To whom correspondence should be addressed. E-mail: maria.fuller{at}adelaide.edu.au.

Background: Fabry disease is an X-linked inborn error of glycosphingolipid catabolism resulting from a deficiency of the lysosomal exoglycohydrolase, -galactosidase. Enzyme replacement therapy is currently available for Fabry disease, but early diagnosis before the onset of irreversible pathology will be mandatory for successful treatment. Presymptomatic detection would be possible through the use of a newborn-screening program. We report on the use of sensitive assays for the measurement of -galactosidase protein and activity and for the protein saposin C, which are diagnostic markers for Fabry disease.

Methods: Two sensitive immunoassays for the measurement of -galactosidase activity and protein were used to determine the concentrations of -galactosidase in dried filter-paper blood spots and plasma samples from control patients and patients with lysosomal storage disorder (LSD).

Results: Fabry hemizygous individuals were clearly identified from control populations by decreases in both -galactosidase activity and protein. Fabry heterozygotes generally fell between the hemizygotes and controls. Including the measurement of saposin C enabled differentiation between Fabry heterozygotes and controls. In blood spots, all Fabry individuals could be distinguished from control blood spots as well as from 16 other LSD patients.

Conclusions: The determination of -galactosidase activity or protein in dried filter-paper blood spots could be used for the diagnosis of Fabry patients. With further validation, these assays could be used for the identification of Fabry patients in newborn-screening programs and may also be suitable for screening high-risk populations.