Other disorders of glycogen metabolism: GLUT2 deficiency and aldolase A deficiency
- William J Craigen, MD, PhD
William J Craigen, MD, PhD
- Professor of Molecular and Human Genetics
- Baylor College of Medicine
- Basil T Darras, MD
Basil T Darras, MD
- Professor of Neurology
- Harvard Medical School
Glycogen is the stored form of glucose and serves as a buffer for glucose needs. It is composed of long polymers of a 1,4-linked glucose, interrupted by a 1,6-linked branch point every 4 to 10 residues. Glycogen is formed in periods of dietary carbohydrate loading and broken down when glucose demand is high or dietary availability is low (figure 1).
There are a number of inborn errors of glycogen metabolism that result from mutations in genes for virtually all of the proteins involved in glycogen synthesis, degradation, or regulation (figure 1). Those disorders that result in abnormal storage of glycogen are known as glycogen storage diseases (GSDs) (table 1).
Glycogen is most abundant in liver and muscle. The major manifestations of disorders of glycogen metabolism affecting the liver are hypoglycemia and hepatomegaly, and the primary features of those defects that affect muscle are muscle cramps, exercise intolerance, easy fatigability, and progressive weakness.
This topic will review two disorders of glycogen metabolism: glucose transporter 2 (GLUT2) deficiency and aldolase A deficiency. An overview of GSDs is presented separately. (See "Overview of inherited disorders of glucose and glycogen metabolism".)
GLUT2 deficiency (MIM #227810), also known as Fanconi-Bickel syndrome, is a rare disorder of glucose homeostasis that leads to accumulation of glycogen in the liver and kidney and glucose and galactose intolerance. GLUT2 is a facilitative, bidirectional transporter. It passively transports intracellular glucose and galactose across the basolateral membrane of cells including hepatocytes, pancreatic beta cells, renal tubular cells, and intestinal epithelial cells by moving the carbohydrate molecule down its concentration gradient . Transient expression of induced apical membrane GLUT2 plays a role separate from sodium-glucose transporter 1 (SGLT1 or SLC5A1) in the absorption of simple sugars in the intestinal mucosa and is a potential target for modulating carbohydrate absorption . Glycogen accumulation in patients with GLUT2 deficiency occurs due to a failure to adequately export glucose generated by glycogen degradation. This inadequate export leads to a marked increase in intracellular glucose that inhibits glycogen degradation. (See "Insulin secretion and pancreatic beta cell function", section on 'Role of glucose'.)
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