scholarly journals Circulating exosomal microRNAs as potential biomarkers of hepatic injury and inflammation in a murine model of glycogen storage disease type 1a

2020 ◽  
Vol 13 (9) ◽  
pp. dmm043364
Author(s):  
Roberta Resaz ◽  
Davide Cangelosi ◽  
Martina Morini ◽  
Daniela Segalerba ◽  
Luca Mastracci ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Murine Model ◽  
Storage Disease ◽  
Hepatocellular Adenoma ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Telomere Maintenance ◽  
Differentially Expressed ◽  
Potential Biomarkers

ABSTRACTMost patients affected by glycogen storage disease type 1a (GSD1a), an inherited metabolic disorder caused by mutations in the enzyme glucose-6-phosphatase-α (G6Pase-α), develop renal and liver complications, including the development of hepatocellular adenoma/carcinoma. The purpose of this study was to identify potential biomarkers of the pathophysiology of the GSD1a-affected liver. To this end, we used the plasma exosomes of a murine model of GSD1a, the LS-G6pc−/− mouse, to uncover the modulation in microRNA expression associated with the disease. The microRNAs differentially expressed between LS-G6pc−/− and wild-type mice, LS-G6pc−/− mice with hepatocellular adenoma and LS-G6pc−/− mice without adenoma, and LS-G6pc−/− mice with amyloidosis and LS-G6pc−/− mice without amyloidosis were identified. Pathway analysis demonstrated that the target genes of the differentially expressed microRNA were significantly enriched for the insulin signaling pathway, glucose and lipid metabolism, Wnt/β-catenin, telomere maintenance and hepatocellular carcinoma, and chemokine and immune regulation signaling pathways. Although some microRNAs were common to the different pathologic conditions, others were unique to the cancerous or inflammatory status of the animals. Therefore, the altered expression of several microRNAs is correlated with various pathologic liver states and might help to distinguish them during the progression of the disease and the development of late GSD1a-associated complications.

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

2021 ◽  
Vol 23 (1) ◽  
pp. 328
Author(s):  
Roberta Resaz ◽  
Davide Cangelosi ◽  
Daniela Segalerba ◽  
Martina Morini ◽  
Paolo Uva ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Hepatocellular Adenoma ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Altered Expression ◽  
Normal Individuals ◽  
Type Ia ◽  
Potential Biomarkers

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.

scholarly journals Normoglycemia alone is insufficient to prevent long-term complications of hepatocellular adenoma in glycogen storage disease type Ib mice

2009 ◽  
Vol 51 (5) ◽  
pp. 909-917 ◽  
Author(s):  
Wai Han Yiu ◽  
Chi-Jiunn Pan ◽  
Paul A. Mead ◽  
Matthew F. Starost ◽  
Brian C. Mansfield ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Hepatocellular Adenoma ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type

scholarly journals DBS Screening for Glycogen Storage Disease Type 1a: Detection of c.648G>T Mutation in G6PC by Combination of Modified Competitive Oligonucleotide Priming-PCR and Melting Curve Analysis

2021 ◽  
Vol 7 (4) ◽  
pp. 79
Author(s):  
Emma Tabe Eko Niba ◽  
Yogik Onky Silvana Wijaya ◽  
Hiroyuki Awano ◽  
Naoko Taniguchi ◽  
Yasuhiro Takeshima ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Melting Curve ◽  
Hepatocellular Adenoma ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Curve Analysis ◽  
Melting Curve Analysis ◽  
Wild Type

Glycogen storage disease type Ia (GSDIa) is an autosomal recessive disorder caused by glucose-6-phosphatase (G6PC) deficiency. GSDIa causes not only life-threatening hypoglycemia in infancy, but also hepatocellular adenoma as a long-term complication. Hepatocellular adenoma may undergo malignant transformation to hepatocellular carcinoma. New treatment approaches are keenly anticipated for the prevention of hepatic tumors. Gene replacement therapy (GRT) is a promising approach, although early treatment in infancy is essential for its safety and efficiency. Thus, GRT requires screening systems for early disease detection. In this study, we developed a screening system for GSDIa using dried blood spots (DBS) on filter paper, which can detect the most common causative mutation in the East-Asian population, c.648G>T in the G6PC gene. Our system consisted of nested PCR analysis with modified competitive oligonucleotide priming (mCOP)-PCR in the second round and melting curve analysis of the amplified products. Here, we tested 54 DBS samples from 50 c.648G (wild type) controls and four c.648T (mutant) patients. This system, using DBS samples, specifically amplified and clearly detected wild-type and mutant alleles from controls and patients, respectively. In conclusion, our system will be applicable to newborn screening for GSDIa in the real world.

scholarly journals Fenofibrate rapidly decreases hepatic lipid and glycogen storage in neonatal mice with glycogen storage disease type Ia

2019 ◽  
Vol 29 (2) ◽  
pp. 286-294 ◽  
Author(s):  
Zollie A Yavarow ◽  
Hye-Ri Kang ◽  
Lauren R Waskowicz ◽  
Boon-Huat Bay ◽  
Sarah P Young ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Hepatocellular Adenoma ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Pharmacological Therapy ◽  
Disease Type ◽  
Hepatic Glycogen ◽  
Alcoholic Fatty Liver ◽  
Type Ia

Abstract Glycogen storage disease type Ia (GSD Ia) is caused by autosomal mutations in glucose-6-phosphatase α catalytic subunit (G6PC) and can present with severe hypoglycemia, lactic acidosis and hypertriglyceridemia. In both children and adults with GSD Ia, there is over-accumulation of hepatic glycogen and triglycerides that can lead to steatohepatitis and a risk for hepatocellular adenoma or carcinoma. Here, we examined the effects of the commonly used peroxisomal proliferated activated receptor α agonist, fenofibrate, on liver and kidney autophagy and lipid metabolism in 5-day-old G6pc −/− mice serving as a model of neonatal GSD Ia. Five-day administration of fenofibrate decreased the elevated hepatic and renal triglyceride and hepatic glycogen levels found in control G6pc −/− mice. Fenofibrate also induced autophagy and promoted β-oxidation of fatty acids and stimulated gene expression of acyl-CoA dehydrogenases in the liver. These findings show that fenofibrate can rapidly decrease hepatic glycogen and triglyceride levels and renal triglyceride levels in neonatal G6pc −/− mice. Moreover, since fenofibrate is an FDA-approved drug that has an excellent safety profile, our findings suggest that fenofibrate could be a potential pharmacological therapy for GSD Ia in neonatal and pediatric patients as well as for adults. These findings may also apply to non-alcoholic fatty liver disease, which shares similar pathological and metabolic changes with GSD Ia.

scholarly journals Natural History of Hepatocellular Adenoma Formation in Glycogen Storage Disease Type I

2011 ◽  
Vol 159 (3) ◽  
pp. 442-446 ◽  
Author(s):  
David Q. Wang ◽  
Laurie M. Fiske ◽  
Caroline T. Carreras ◽  
David A. Weinstein
Keyword(s):  
Natural History ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Hepatocellular Adenoma ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Type I ◽  
History Of
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