Biochemical and clinical aspects of glycogen storage diseases

Abstract

The synthesis of glycogen represents a key pathway for the disposal of excess glucose while its degradation is crucial for providing energy during exercise and times of need. The importance of glycogen metabolism is also highlighted by human genetic disorders that are caused by mutations in the enzymes involved. In this review, we provide a basic summary on glycogen metabolism and some of the clinical aspects of the classical glycogen storage diseases. Disruptions in glycogen metabolism usually result in some level of dysfunction in the liver, muscle, heart, kidney and/or brain. Furthermore, the spectrum of symptoms observed is very broad, depending on the affected enzyme. Finally, we briefly discuss an aspect of glycogen metabolism related to the maintenance of its structure that seems to be gaining more recent attention. For example, in Lafora progressive myoclonus epilepsy, patients exhibit an accumulation of inclusion bodies in several tissues, containing glycogen with increased phosphorylation, longer chain lengths and irregular branch points. This abnormal structure is thought to make glycogen insoluble and resistant to degradation. Consequently, its accumulation becomes toxic to neurons, leading to cell death. Although the genes responsible have been identified, studies in the past two decades are only beginning to shed light into their molecular functions.

Periodontal Manifestation of Type Ib Glycogen Storage Disease: A Rare Case Report

“…1 There are over 15 types of GSDs classified on the basis of enzyme/pathway involved and the Online Mendelian Inheritance in Man number. 2 Neutropenia is a specific manifestation of GSD-Ib which is the only type that is associated with periodontal symptoms. 2 Besides, neutropenia is one of the myeloid dysfunctions observed in GSD-Ib.…”

“…2 Neutropenia is a specific manifestation of GSD-Ib which is the only type that is associated with periodontal symptoms. 2 Besides, neutropenia is one of the myeloid dysfunctions observed in GSD-Ib. Glucose 6phosphate transporter expression in bone marrow and neutrophils are required for normal myeloid functions.…”

“…1 GSD is a group of inherited disorders that involves deficiencies in the enzymes that metabolize glycogen; there are >15 types of glycogen storage diseases classified on the basis of the enzyme deficiency and the affected tissue. 2 Glycogen storage disease Type I (Von Gierke disease) autosomal recessive inborn error of carbohydrate metabolism caused by defects in the glucose-6-phosphate transporter (G6PT)/glucose-6-phosphatase (G6Pase) complex. 3 There are four subtypes (a, b, c, and d) of GSD-I depending on abnormality in G6Pase.…”

Management of Children with Glycogen Storage Disease (Liver Involvement Forms). Best Practice Guidelines

“…Он содержит 5 экзонов и занимает около 12,5 kb геномной ДНК. Тип наследования -аутосомнорецессивный [4,8].…”

“…Глюкозо-6-фосфатаза катализирует конечную реакцию как глюконеогенеза, так и гидролиза гликогена, расщепляя глюкозо-6-фосфат на глюкозу и неорганический фосфат и являясь единственным источником обеспечения организма большими концентрациями глюкозы. Гипогликемия развивается даже при кратковременном голодании из-за блокады гликогенолиза и глюконеогенеза, происходит также накопление гликогена в печени, почках и слизистой оболочке кишечника, приводя к дисфункции этих органов [8,9]. Накопление субстрата блокированной реакции, глюкозо-6-фосфата, стимулирует гликолиз и накопление лактата, который, синтезируясь в эритроцитах и мышечной ткани, не может быть превращен в глюкозу в печени (блокада глюконеогенеза).…”