49
Metabolic Disorders Induced by Impaired Glycogen Metabolism
Glycogen, also known as animal starch, is a high molecular weight polysaccharide,
containing up to 10,000 glucose residues [25]. It is actually a mobilized storage
form of glucose in the liver and skeletal muscles that can provide energy by degrading into glucose residues [26]. The glucose units in the structure of glycogen are
bonded via α-1,4-glycosidic bonds in linear chains and at branches via α-1,6glycosidic linkages [27]. Glycogenesis, a metabolic pathway of glycogen synthesis,
is regulated by hormone insulin and catalyzed by glycogen synthase enzyme [28],
whereas glycogenolysis is a metabolic pathway of glycogen degradation, modulated by glucagon hormone, occurring in liver and muscles for balancing of blood
sugar level and provision of energy. The process of glycogenolysis is catalyzed by
glycogen phosphorylase [9].
Glycogen Storage Diseases
Glycogen storage diseases (GSDs), also known as glycogenosis, are a group of
inherited disorders affecting glycogen metabolism. Liver and skeletal muscles being
the major organs for the metabolism of glycogen are also affected [10, 29]. GSDs
are caused by genetic deficiencies in the enzymes which are involved in the metabolic pathways of glycogen, resulting into abnormal amount and/or structure of
glycogen [30]. They are autosomal recessive disorders. GSDs are numbered in
accordance with their discovery and they were considered similar in pathology but
later on they were appeared not to be similar in pathology. GSDs having a lower
number have a severe end of the spectrum, whereas those having a greater number
show severe fasting intolerance [31]. The initial treatment in all types of GSDs
involves the immediate correction of hypoglycemia [32].
GSD Type 0
It is a rare disorder that occurs due to the deficiency of glycogen synthase which is
required for glycogen synthesis. After consuming carbohydrates, glycogen is not
formed from glucose which leads to postprandial hyperglycemia and hyperlactatemia. Its clinical presentations are pallor, lethargy, nausea, vomiting, and convulsions in some cases [33]. Children in infancy with this disorder are usually
asymptomatic. This is the only type of GSD which is not associated with hypoglycemia and hepatomegaly as it causes a decrease in liver glycogen. This disorder is
caused by a mutation in the glycogen synthase 2 gene [34].
2 Impaired Carbohydrate Metabolism in Metabolic Disorders
Metabolic Disorders Induced by Impaired Glycogen Metabolism
Glycogen, also known as animal starch, is a high molecular weight polysaccharide,
containing up to 10,000 glucose residues [25]. It is actually a mobilized storage
form of glucose in the liver and skeletal muscles that can provide energy by degrading into glucose residues [26]. The glucose units in the structure of glycogen are
bonded via α-1,4-glycosidic bonds in linear chains and at branches via α-1,6glycosidic linkages [27]. Glycogenesis, a metabolic pathway of glycogen synthesis,
is regulated by hormone insulin and catalyzed by glycogen synthase enzyme [28],
whereas glycogenolysis is a metabolic pathway of glycogen degradation, modulated by glucagon hormone, occurring in liver and muscles for balancing of blood
sugar level and provision of energy. The process of glycogenolysis is catalyzed by
glycogen phosphorylase [9].
Glycogen Storage Diseases
Glycogen storage diseases (GSDs), also known as glycogenosis, are a group of
inherited disorders affecting glycogen metabolism. Liver and skeletal muscles being
the major organs for the metabolism of glycogen are also affected [10, 29]. GSDs
are caused by genetic deficiencies in the enzymes which are involved in the metabolic pathways of glycogen, resulting into abnormal amount and/or structure of
glycogen [30]. They are autosomal recessive disorders. GSDs are numbered in
accordance with their discovery and they were considered similar in pathology but
later on they were appeared not to be similar in pathology. GSDs having a lower
number have a severe end of the spectrum, whereas those having a greater number
show severe fasting intolerance [31]. The initial treatment in all types of GSDs
involves the immediate correction of hypoglycemia [32].
GSD Type 0
It is a rare disorder that occurs due to the deficiency of glycogen synthase which is
required for glycogen synthesis. After consuming carbohydrates, glycogen is not
formed from glucose which leads to postprandial hyperglycemia and hyperlactatemia. Its clinical presentations are pallor, lethargy, nausea, vomiting, and convulsions in some cases [33]. Children in infancy with this disorder are usually
asymptomatic. This is the only type of GSD which is not associated with hypoglycemia and hepatomegaly as it causes a decrease in liver glycogen. This disorder is
caused by a mutation in the glycogen synthase 2 gene [34].
2 Impaired Carbohydrate Metabolism in Metabolic Disorders