Polycystic kidney features of the renal pathology in glycogen storage disease type I: possible evolution to renal neoplasia

AbstractGlycogen storage disease type I (GSDI) is a rare genetic pathology characterized by glucose-6 phosphatase (G6Pase) deficiency, translating in hypoglycemia during short fasts. Besides metabolic perturbations, GSDI patients develop long-term complications, especially chronic kidney disease (CKD). In GSDI patients, CKD is characterized by an accumulation of glycogen and lipids in kidneys, leading to a gradual decline in renal function. At a molecular level, the activation of the renin-angiotensin system is responsible for the development of renal fibrosis, eventually leading to renal failure. The same CKD phenotype was observed in a mouse model with a kidney-specific G6Pase deficiency (K.G6pc −/− mice). Furthermore, GSDI patients and mice develop frequently renal cysts at late stages of the nephropathy, classifying GSDI as a potential polycystic kidney disease (PKD). PKDs are genetic disorders characterized by multiple renal cyst formation, frequently caused by the loss of expression of polycystic kidney genes, such asPKD1/2 andPKHD1. Interestingly, these genes are deregulated in K.G6pc −/− kidneys, suggesting their possible role in GSDI cystogenesis. Finally, renal cysts are known to predispose to renal malignancy development. In addition, HNF1B loss is a malignancy prediction factor. Interestingly,Hnf1b expression was decreased in K.G6pc −/− kidneys. While a single case of renal cancer has been reported in a GSDI patient, a clear cell renal carcinoma was re...
Source: Journal of Inherited Metabolic Disease - Category: Internal Medicine Source Type: research