Exosomal MicroRNAs as Potential Biomarkers of Hepatic Injury and Kidney Disease in Glycogen Storage Disease Type Ia Patients.

Roberta Resaz,Annalisa Sechi,David A Weinstein,Martina Morini,Sabrina Paci,Maria Carla Bosco,Maja Di Rocco,Ana Estrella,Corbinian Wanner,Daniela Melis,Young Mok Lee,Giuseppe Banderali,Daniela Segalerba,Davide Cangelosi,Paolo Uva,Alessandra Eva

doi:10.3390/ijms23010328

Abstract

Glycogen storage disease type Ia (GSDIa) is an inherited metabolic disorder caused by mutations in the enzyme glucose-6-phosphatase-α (G6Pase-α). Affected individuals develop renal and liver complications, including the development of hepatocellular adenoma/carcinoma and kidney failure. The purpose of this study was to identify potential biomarkers of the evolution of the disease in GSDIa patients. To this end, we analyzed the expression of exosomal microRNAs (Exo-miRs) in the plasma exosomes of 45 patients aged 6 to 63 years. Plasma from age-matched normal individuals were used as controls. We found that the altered expression of several Exo-miRs correlates with the pathologic state of the patients and might help to monitor the progression of the disease and the development of late GSDIa-associated complications.

Highlights

Glycogen storage disease type Ia (GSDIa) is a rare disease caused by mutations in glucose-6-phosphatase-α (G6Pase-α), an enzyme expressed in the liver, kidney and intestine, which is fundamental in the terminal steps of gluconeogenesis and glycogenolysis
We have identified Exo-miRs involved in renal pathology that are deregulated in GSDIa patients, and compatible with the progressive severe kidney disease occurring in GSDIa
Our analysis reveals that the Exo-miRs that are significantly modulated in GSDIa patients regulate genes connected with the biological pathways previously identified by the proteomic analysis of LS-G6pc−/− mice livers as being associated with the reprogramming of glucose-6-phosphate and with tumor development and progression

Summary

Introduction

Glycogen storage disease type Ia (GSDIa) is a rare disease caused by mutations in glucose-6-phosphatase-α (G6Pase-α), an enzyme expressed in the liver, kidney and intestine, which is fundamental in the terminal steps of gluconeogenesis and glycogenolysis. The lack of a functional G6Pase-α results in the ineffective regulation of glucose homeostasis [1]. GSDIa is a metabolic disorder that causes hypoglycemia, hyperlipidemia, hyperuricemia, and lactic acidemia. The accumulation of glycogen in the liver and kidney causes hepatomegaly and kidney enlargement. The disease can be managed by a very strict diet to prevent hypoglycemia, consisting of continuous nocturnal gastric drip feeding and/or the frequent oral administration of meals containing complex carbohydrates and uncooked cornstarch [2]

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