Glycogen storage diseases: New perspectives

Abstract

Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. Type Ia involves the liver, kidney and intestine (and Ib also leukocytes), and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type IIIa involves both the liver and muscle, and IIIb solely the liver. The liver symptoms generally improve with age. Type IV usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type VI and IX are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia. Type XI is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type II is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types V and VII involve only the muscle.

Targeted deletion of liver glucose-6 phosphatase mimics glycogen storage disease type 1a including development of multiple adenomas

“…In parallel, there is a rapid increase in plasma triglycerides, cholesterol, lactic, and uric acids, as also observed in human GSD1a patients and in total G6pc knock-out mice [3,4]. Together with the absence of kidney and gut deficiency and phenotype in L-G6pc -/-mice, this strongly suggests that the liver deficiency may be fully responsible for the deregulation of plasma parameters in GSD1a.…”

“…G6Pase is an essential enzyme of endogenous glucose production. Patients affected with GSD1 are therefore unable to maintain blood glucose concentration outside the time of meals and suffer from severe hypoglycaemic episodes if they are not managed by continuous feeding [2][3][4]. GSD type 1a and type 1b respectively correspond to inherited mutations in the genes that encode the catalytic subunit (G6PC) and the transporter unit (G6PT) of the G6Pase system [1,2,5,6].…”

“…Targeted deletion of liver glucose-6 phosphatase mimics glycogen storage disease type 1a including development of multiple adenomas Elodie Mutel [1][2][3] , Aya Abdul-Wahed 1-3 , Nirilanto Ramamonjisoa N. [2][3][4] …”

Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing

“…3 The overall incidence of GSD in the population is estimated at 1 case per 2,000-43,000. 1 Liver-affecting GSD types involve hepatomegaly and hypoglycemia, with the consequence of poor glucose distribution throughout the body. Patients with muscle-and heart-affecting GSD experience exercise intolerance, often followed by notable rhabdomyolysis.…”

Pyrrolidine dithiocarbamate enhances hepatic glycogen synthesis and reduces FoxO1-mediated gene transcription in type 2 diabetic rats

“…When glucose is given orally, the liver may dispose of as much as one-third of the glucose load (6,17). During the starvation or fasting state the level of insulin decreases, whereas those of glucagon and glucocorticoids rise, thereby leading to reduced glucose uptake by peripheral tissues and increased hepatic gluconeogenesis and glucose output to prevent hypoglycemia (24). Because the liver plays such a key role in the maintenance of glucose homeostasis (29), it is important to identify pharmacological agents that could regulate hepatic glucose metabolism.…”