50
GSD Type I
It is, also known as von Gierke’s disease, the most common hepatic GSD having a
mortality rate of 1/100,000 in a live birth. Glucose-6-phosphatase deficiency is its
leading cause, the enzyme necessary for the conversion of G6P to glucose and Pi
[35]. This enzyme is necessary for the catalysis of the last step in both glycogenesis
and glycogenolysis. Due to this enzyme deficiency, G6P accumulates leading to
enhanced lactate production [31]. It has further two subtypes, GSDIa caused by a
mutation in the subunit G6Pase-alpha and is a true enzyme defect and GSDIb due
to the defect in G6P translocase and a transport defect. Hypoglycemia, hepatomegaly, hyperlipidemia, and lactic acidosis are common clinical presentations [31, 35].
The symptoms usually appear during infancy [36].
GSD Type II
This disorder, also known as Pompe disease, is caused by acid-α-glucosidase [37]
which leads to lysosomal glycogen accumulation in skeletal muscles, smooth muscles, heart, and in the nervous system [38]. It is a serious and fatal disorder. It is also
termed as progressive neuromuscular disorder and can occur at any age and have a
mortality rate of 1 in 40,000–600,000. GSD type II is also associated with cardiac
hypertrophy and hepatomegaly. Infants with this disease often fail to achieve developmental milestones like standing, sitting, and walking due to loss in muscle strength [39].
GSD Type III
GSD type III, also known as Cori’s disease, is caused by a deficiency in glycogen
debranching enzyme (GDE) which is involved in glycogenolysis [40]. Due to this
enzymatic deficiency glycogen accumulates in the muscles and liver [41]. The
major complication of this disorder is hypertrophic cardiomyopathy [42]. In 85% of
cases, the activity of GDE is absent in both liver and skeletal muscles and in 15% of
cases, only the liver is involved [43]. Hypoglycemia, cirrhosis, hyperlipidemia,
ketosis, myopathy, and hepatosplenomegaly are its common clinical presentations.
At adolescence, hypoglycemic effects decrease but exercise intolerance and cardiomyopathy worsen [10, 44].
GSD Type IV
It is, also known as Anderson’s disease or amylopectinosis, a rare autosomal disease, which results from the deficiency in glycogen branching enzyme (GBE) which
causes accumulation of abnormal glycogen amylopectin which is a plant starch
[45]. It is caused by a mutation in the GBE1 gene. Clinical presentations include
hepatosplenomegaly, failure to thrive, muscular atrophy, hypotonia, cardiopathy,
H. Sharif et al.
GSD Type I
It is, also known as von Gierke’s disease, the most common hepatic GSD having a
mortality rate of 1/100,000 in a live birth. Glucose-6-phosphatase deficiency is its
leading cause, the enzyme necessary for the conversion of G6P to glucose and Pi
[35]. This enzyme is necessary for the catalysis of the last step in both glycogenesis
and glycogenolysis. Due to this enzyme deficiency, G6P accumulates leading to
enhanced lactate production [31]. It has further two subtypes, GSDIa caused by a
mutation in the subunit G6Pase-alpha and is a true enzyme defect and GSDIb due
to the defect in G6P translocase and a transport defect. Hypoglycemia, hepatomegaly, hyperlipidemia, and lactic acidosis are common clinical presentations [31, 35].
The symptoms usually appear during infancy [36].
GSD Type II
This disorder, also known as Pompe disease, is caused by acid-α-glucosidase [37]
which leads to lysosomal glycogen accumulation in skeletal muscles, smooth muscles, heart, and in the nervous system [38]. It is a serious and fatal disorder. It is also
termed as progressive neuromuscular disorder and can occur at any age and have a
mortality rate of 1 in 40,000–600,000. GSD type II is also associated with cardiac
hypertrophy and hepatomegaly. Infants with this disease often fail to achieve developmental milestones like standing, sitting, and walking due to loss in muscle strength [39].
GSD Type III
GSD type III, also known as Cori’s disease, is caused by a deficiency in glycogen
debranching enzyme (GDE) which is involved in glycogenolysis [40]. Due to this
enzymatic deficiency glycogen accumulates in the muscles and liver [41]. The
major complication of this disorder is hypertrophic cardiomyopathy [42]. In 85% of
cases, the activity of GDE is absent in both liver and skeletal muscles and in 15% of
cases, only the liver is involved [43]. Hypoglycemia, cirrhosis, hyperlipidemia,
ketosis, myopathy, and hepatosplenomegaly are its common clinical presentations.
At adolescence, hypoglycemic effects decrease but exercise intolerance and cardiomyopathy worsen [10, 44].
GSD Type IV
It is, also known as Anderson’s disease or amylopectinosis, a rare autosomal disease, which results from the deficiency in glycogen branching enzyme (GBE) which
causes accumulation of abnormal glycogen amylopectin which is a plant starch
[45]. It is caused by a mutation in the GBE1 gene. Clinical presentations include
hepatosplenomegaly, failure to thrive, muscular atrophy, hypotonia, cardiopathy,
H. Sharif et al.