AR

Glycogen Storage Disorders Overview

  • Introduction to Glycogen

    • Glycogen is the storage form of glucose in the body, primarily found in the liver and skeletal muscles.
    • It consists of branched chains of glucose monomers linked together.

  • Metabolism of Glycogen

    • Glycogen can be converted to glucose when needed for energy.
    • Glycogenolysis: Process by which glycogen is broken down to glucose-1-phosphate and subsequently to glucose.
    • Glycolysis: The breakdown of glucose into pyruvate to generate energy.
    • Enzymatic regulation is critical in these metabolic pathways.

  • Glycogen Storage Disorders (GSDs)

    • These disorders arise from issues in the enzymes that regulate glycogen metabolism.
    • There are over 15 types of GSDs, each associated with mutations in specific enzymes.
    • Common types include:
    • Type 1 (Von Gierke's disease): Affects glucose-6-phosphatase enzyme.
    • Type 2 (Pompe disease): Involves the lysosomal enzyme acid alpha-glucosidase (GAA).
    • Type 5 (McArdle disease): Results from deficiency of glycogen phosphorylase.
    • The heterogeneity of GSDs means they can be caused by mutations in different genes.

  • Clinical Impact of GSDs

    • Symptoms vary depending on the type but may include muscle weakness, hypoglycemia, and organ enlargement.
    • The body struggles to either break down or transport glycogen properly.

  • Genetics of GSDs

    • Genetic variety among individuals can lead to different severity of symptoms (expressivity) and different presentations (penetrance).
    • Genetic complementation: Occurs when affected parents with different mutations can have unaffected children due to inheritance of functional alleles from each parent.

  • Key Terms

    • Heterogeneity: Referring to genetic disorders that can result from mutations in multiple unrelated genes.
    • Expressivity: Variation in the severity of the phenotype expressed by individuals with the same genotype.
    • Penetrance: The proportion of individuals with a particular genotype that actually exhibit the phenotype.
    • Pleiotropy: A single gene mutation leading to multiple phenotypic effects.

  • Research and Future Directions

    • The movie