Background/aims: Alpha-galactosidase A (alpha-GLA) deficiency (Fabry disease) is an X-linked lysosomal storage disorder. The associated visceral complications are progressive and multiorgan; renal involvement is common, usually leading to end-stage renal failure (ESRF). The reported benefits of specific enzyme replacement therapy (ERT) indicate the importance of screening for Fabry disease in high-risk populations, as this approach should make it possible to identify other family members with little or no clinical features of the disease, and for them to be considered for early preventive treatment.
Methods: We screened for Fabry disease in 106 patients on hemodialysis in our hospital-based hemodialysis unit. We did this by measuring alpha-GLA enzyme activity in blood leukocytes taken from each patient and we then carried out gene analysis when indicated.
Results: We were able to discover 1 patient with low residual alpha-GLA activity (a prevalence of 0.94%). Alpha-GLA gene analysis identified a point mutation within the coding region producing a N215S amino acid substitution in the protein. Among the relatives of this index case, molecular testing found 7 family members with the same N215S alpha-GLA mutation. Of these, 3 had reduced alpha-GLA activity and clinical features of Fabry disease, and for which ERT was subsequently given.
Conclusion: Screening for Fabry disease is simple and although the yield is small, it is potentially significant and of possible benefit to the relatives of affected cases in this 'at-risk' ESRF population, many of who do not have a clear renal diagnosis.