Phosphoglycerate kinase deficiency and phosphoglycerate mutase deficiency
- Basil T Darras, MD
Basil T Darras, MD
- Professor of Neurology
- Harvard Medical School
- William J Craigen, MD, PhD
William J Craigen, MD, PhD
- Professor of Molecular and Human Genetics
- Baylor College of Medicine
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. 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 phosphoglycerate kinase (PGK) deficiency and phosphoglycerate mutase (PGAM) deficiency (GSD X). An overview of disorders of glycogen metabolism is presented separately. (See "Overview of inherited disorders of glucose and glycogen metabolism".)
PHOSPHOGLYCERATE KINASE DEFICIENCY
PGK catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate. One molecule of adenosine triphosphate (ATP) is generated in the process. Deficiency of PGK (MIM #311800) results in three different clinical presentations. (See 'Clinical features' below.)
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