Background
Fabry disease (FD) is an X‐linked lysosomal storage disorder caused by enzyme Alpha‐Galactosidase A (α‐Gal‐A) deficiency, due mutations in GLA gene. Progressive glycolipid accumulation leads to damage in kidney and other organs. The aim of this study was to estimate the prevalence of Fabry disease in Argentinean male patients undergoing dialysis.
Methods
A prospective screening study was carried out measuring the α‐Gal‐A activity in dried blood spot (DBS) samples of male patients undergoing dialysis from Argentina. Those patients in which DBS α‐Gal‐A level was low (<4.0 μmol/hr/L), underwent GLA genetic testing for diagnosis confirmation.
Results
Nine thousand six hundred and four dialysis male patients from 264 centers distributed over 20 of the 23 provinces of Argentina were investigated. Twenty‐four patients showed a decreased or absent α‐Gal‐A activity in DBS and although genetic analysis found a variant in the GLA gene in every one of these patients, we could confirm FD diagnosis in 22 cases.
Conclusion
The prevalence rate of FD found in Argentinean male dialysis patients was 0.23%. Classic phenotype was observed in 73% of patients, whereas the remaining 27% presented as late‐onset variant. This was the largest study carried out in dialysis patients from a same country at a worldwide level and the first study performed in Argentina.
No difference in symptomatology was discernible between boys and girls. Podocyturia was detectable in children serving as a possible early marker of kidney injury. LysoGb3 was elevated in all cases, emphasizing the importance for diagnosis especially in female patients with normal αGal A activity. A possible association between lysoGb3 and symptom severity and histological involvement in kidney biopsy should be assessed in prospective studies with enough statistical power to determine if lysoGb3 can be used to predict nephropathy in children with Fabry disease.
Fabry disease is an X linked disorder of metabolism due to deficient a-galactosidase A activity. Enzyme replacement therapy (ERT) with agalsidase Beta was approved by EMA in FDA in 2003. Patients and methods: Six patients were enrolled. Baseline data was measured for renal, cardiac, and cerebrovascular functioning. We compared baseline quality of life scales with the current results. These parameters were assessed during the 10 years of follow-up period.Results: Before ERT four patients showed normal eGFR, one stage 2 of CKD, and one hyperfiltration stage. All presented microalbuminuria and just two cases showed proteinuria. After 10 years of ERT, no patient showed decrease in renal functioning. One patient decreased from proteinuria to microalbuminuria range. Before treatment one case showed left ventricular (LV) hypertrophy and LV Mass Index was abnormal in two female patients. After 10 years echocardiographic values did not present progression to LVH and one female showed regression to normal values of LV posterior wall and interventricular septum. Brain MRI showed ischemic lesions in one female and vertebrobasilar dolichoectasia in one male. From baseline and during the follow-up period MRI did not progress to new ischemic lesions and there were no clinical signs of cerebrovascular damage. After 10 years quality of life showed improvement in all domains measured.Conclusion: Early treatment of agalsidase Beta is related to a better outcome regarding stability and regression of signs and symptoms in Fabry disease. Our results in patients with mild organ involvement showed good outcomes and support an early and continuous ERT.
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