Novel Pathogenic Variant of Fabry Disease in a Family with Parapelvic Cysts

Abstract

Background: Fabry's Disease (FD) is a rare, multi-organ lysosomal disease, caused by the deficiency of the enzyme α-galactosidase A. This leads to the accumulation of glycosphingolipids, particularly globotriaosylsphingosine (Lyso-Gb3), in visceral tissues and vascular endothelium throughout the body, with renal, cardiac, and central nervous system damage such that quality and expectancy of life are impaired. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. We report the case of a patient with hypertension and proteinuria whose diagnosis of Fabry's disease was suspected due to the ultrasound finding of parapelvic cysts. Case presentation: A 41-year-old man with proteinuria and hypertension presented to our outpatient Department. The patient underwent a genetic investigation for Fabry due to the ultrasound finding of parapelvic cysts. We found a novel mutation c.160del in exon 1 of GLA gene with aminoacidic change in p. (Asp55ThrfsTer66). The new mutation was also found in the mother and his brother. In males, the elevated accumulation of LysoGB3 was associated with the presence of renal parapelvic cysts. Conclusion: This mutation is not reported in Fabry disease-associated mutation databases and has not been previously described in the literature but, the absent enzyme activity found in our patient, the significant blood accumulation of LysoGb3, as well as the type of mutation suggest its pathogenetic role. In addition, the novel mutation would appear to correlate with the occurrence of pelvic cysts in male subjects. Therefore Fabry’s disease should be suspected in male patients with hypertension, proteinuria and ultrasonographic finding of parapelvic cysts, especially in patients with otherwise unexplained cardiac, neurologic and/or ocular abnormalities. Further studies are needed to corroborate the finding.