Cardiac involvement is a well-known feature in several glycogen storage diseases (GSDs) such as types II, III, IV, and IX and PRKAG2, a gene that
encodes the regulatory γ2-subunit of AMP-activated protein kinase (AMPK)
, which, when mutated, causes glycogen storage cardiomyopathy.
What is glycogen storage cardiomyopathy?
Glycogen storage disease type III (GSD III) due to debranching enzyme deficiency presenting usually with hepatomegaly and hypoglycemia may be responsible for severe cardiomyopathy which is often fatal. Current treatment of GSD III is based on frequent high-carbohydrate meals that have no effect on the cardiomyopathy.
Which glycogen storage disease is characterized by cardiomegaly?
In the classic infantile form of
Pompe disease
, clinically significant glycogen storage occurs in cardiac muscle. Over time, cardiomegaly with LV thickening occurs, eventually leading to outflow tract obstruction. Glycogen storage in skeletal muscle leads to hypotonia and weakness.
Why does glycogen storage disease cause hyperuricemia?
Hyperuricemia and gout occur commonly in cases of GSD I. A decreased renal excretion of urate secondary to lactic academia and ketonaemia and
an elevated production of uric acid
account for hyperuricemia [15].
What is the effect of glycogen storage disease IV Amylopectinosis on levels of glycogen in the liver?
Glycogen accumulation
in the liver leads to hepatomegaly and interferes with liver functioning
. The inability of muscle cells to break down glycogen for energy leads to muscle weakness and wasting. Generally, the severity of the disorder is linked to the amount of functional glycogen branching enzyme that is produced.
Which glycogen storage disease affects heart?
GSD III
is a rare disease of variable clinical severity affecting primarily the liver, skeletal muscle, and heart (Chen et al. 2009). It is caused by deficient activity of glycogen debranching enzyme, which is a key enzyme in glycogen degradation.
What is glycogen storage disease?
Glycogen storage disease (GSD) is
a rare condition that changes the way the body uses and stores glycogen, a form of sugar or glucose
. Glycogen is a main source of energy for the body. Glycogen is stored in the liver. When the body needs more energy, certain proteins called enzymes break down glycogen into glucose.
Is glycogen storage disease a metabolic disorder?
A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a
metabolic disorder caused by an enzyme deficiency
affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles and/or liver cells. GSD has two classes of cause: genetic and acquired.
What is the most common glycogen storage disease?
Types of Glycogen Storage Disease
Type I (Von Gierke disease)
– this is the most common type of glycogen storage disease, and accounts for 90% of all glycogen storage disease cases. Type II (Pompe’s disease, acid maltase deficiency) Type III (Cori’s disease)
What is the process of Glycogenesis?
Glycogenesis is the
process of glycogen synthesis
, in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in response to high glucose levels.
Why does a deficiency in glucose-6-phosphatase lead to hyperuricemia?
…the absence of the enzyme glucose-6-phosphatase, which regulates the release of the simple sugar glucose from glycogen stored in the liver. This results in
an abnormal accumulation of glycogen in the liver
, causing the liver to enlarge and producing symptoms of hypoglycemia (low blood sugar) and hyperuricemia (gout).
What causes von Gierke disease?
Von Gierke disease occurs
when the body lacks the protein (enzyme) that releases glucose from glycogen
. This causes abnormal amounts of glycogen to build up in certain tissues. When glycogen is not broken down properly, it leads to low blood sugar.
Why does von Gierke disease cause hyperuricemia?
Triglyceride levels in GSD I can reach several times normal and serve as a clinical index of “metabolic control”. Hyperuricemia results from
a combination of increased generation and decreased excretion of uric acid
, which is generated when increased amounts of G6P are metabolized via the pentose phosphate pathway.
What is the effect of a defective Debranching enzyme in Cori’s disease GSD III )?
What are the symptoms of debrancher enzyme deficiency? This disease principally affects the liver. It
causes swelling of the liver, slowing of growth, low blood sugar levels and, sometimes, seizures
. In children, these symptoms often improve around puberty.
What enzyme is affected by Pompe disease?
Pompe disease happens because of a mutation (a change) in a gene that helps make an enzyme called
alpha-glucosidase
. This enzyme breaks down a type of glucose called glycogen . When the enzyme is not made properly, glycogen builds up in the body’s cells.
What does Gaucher disease affect?
It is a disorder passed from parents to children (inherited). It
causes fatty substances called lipids to build up in certain organs such as the spleen and liver
. Organs can become very large and not work well. It can also affect the lungs, brain, eyes, and bones.
Is cardiomyopathy cardiovascular disease?
Cardiomyopathy (kahr-dee-o-my-OP-uh-thee) is
a disease of the heart muscle
that makes it harder for your heart to pump blood to the rest of your body. Cardiomyopathy can lead to heart failure. The main types of cardiomyopathy include dilated, hypertrophic and restrictive cardiomyopathy.
Which gene causes glycogen storage disease?
Mutations in the
glucose-6-phosphatase-alpha (G6PC) gene
that cause type Ia glycogen storage disease.
Is glycogen present in heart?
Glycogen Metabolism
Glycogen occupies about 2% of the cell volume of the adult and 30% of the cell volume of the fetal and newborn cardiomyocyte. Unlike liver and skeletal muscle,
heart muscle increases its glycogen content with fasting
.
What is Anderson disease?
Andersen disease is also known as
glycogen storage disease (GSD) type IV
. It is caused by deficient activity of the glycogen-branching enzyme, resulting in accumulation of abnormal glycogen in the liver, muscle, and/or other tissues.
What causes McArdle’s disease?
What causes McArdle disease? McArdle disease is an inherited disease. It
results from changes (mutations) in the gene for the enzyme muscle phosphorylase
. Your muscle cells can’t make this enzyme.
What are the symptoms of glycogen storage disease type 1?
What are the symptoms of GSD I? Children born with GSD I typically exhibit
growth failure, chronic hunger, fatigue, irritability, an enlarged liver, and a swollen abdomen
. Blood tests may indicate low blood sugar concentration and higher than normal levels of lipids and uric acid.
How is glycogen storage disease treated?
In general,
no specific treatment exists to cure glycogen
storage diseases (GSDs). In most cases, the mainstay of management involves measures to reduce hypoglycemia, including frequent meals and consumption of uncooked cornstarch.
Which of the following enzymes leads to a glycogen storage disease known as Tarui’s disease?
Glycogen storage disease type 3 (Forbes disease or GSD3) is a glycogen storage disorder that is inherited as an autosomal recessive disorder. Symptoms are caused by missing
enzyme amylo-1,6 glucosidase (debrancher enzyme)
.
What causes glycogen storage disease type XI?
Glycogen storage disease type XI (GSD-XI) is an autosomal recessive disorder of glycogen metabolism. GSD-XI is caused by
mutations in the LDHA gene, which encodes lactate dehydrogenase
. Molecular characterization of genetic mutation in human lactate dehydrogenase-A (M) deficiency.
How is von Gierke disease diagnosed?
Definitive diagnosis of Von Gierke Disease is by
liver biopsy (examination of liver tissue), and assay of enzyme (glucose-6-phosphatase) activity
. Gene testing, a recently available test that can detect mutations, provides a non-invasive technique for definitive diagnosis.
What are the reactions involved in glycogenesis?
The reaction involves
the cleavage of the α-(1 → 4) glycosidic linkage between the terminal glucose residue of a branch and its neighbour by phosphorolysis
. The products of the reaction are glucose 1-phosphate which retains the α-configuration and a glycogen molecule which is one glucose residue smaller.
What is the purpose of gluconeogenesis?
Publisher Summary. Gluconeogenesis refers to
synthesis of new glucose from noncarbohydrate precursors
, provides glucose when dietary intake is insufficient or absent. It also is essential in the regulation of acid-base balance, amino acid metabolism, and synthesis of carbohydrate derived structural components.
How does insulin promote glycogenesis?
Insulin promotes
dephosphorylation and activation of glycogen synthase (GS) by inactivating glycogen synthase kinase (GSK) 3 through phosphorylation
. Insulin also promotes glucose uptake and glucose 6-phosphate (G-6-P) production, which allosterically activates GS.
What causes Glycogenesis?
Glycogenesis takes place when blood glucose levels are sufficiently high to allow excess glucose to be stored in liver and muscle cells. Glycogenesis is stimulated by
the hormone insulin
.
What type of doctor treats glycogen storage disease?
After diagnosis, children with GSD are usually cared for by several specialists, including
specialists in endocrinology and metabolism
. Specific dietitians with expertise in this disease should be involved.
Why does Lactic acidosis occurs in von Gierke’s disease?
Von Gierke’s disease (described by von Gierke in 1929) represents the largest group of glycogen storage disorders (GSDs). There is an enzyme defect in glucose-6-phosphatase so that
glucose-6-phosphate cannot be converted into free glucose but is metabolised to lactic acid or incorporated into
glycogen.
Is G6PD a glycogen storage disease?
Glucose-6-phosphatase deficiency (G6PD, MIM #232200), also known as von Gierke disease, is
a glycogen storage disease
(GSD). It was the first GSD to have the responsible enzyme defect identified and therefore is designated GSD I (table 1).
What enzyme causes von Gierke disease?
Von Gierke disease is an autosomal recessive disorder caused by a deficiency of
the enzyme glucose-6-phosphate translocase
, which transports glucose-6-phosphate into the endoplasmic reticulum for further metabolism. In glycogen storage disease type 1b (GSD-1b), glucose-6-phosphate accumulates intracellularly.
What is the purpose of glucose-6-phosphatase?
The classical role of glucose-6-phosphatase in liver and kidney is
the production of glucose for release into blood
. In liver, glucose-6-phosphatase catalyses the terminal step of glycogenolysis and gluconeogenesis.
What happens when glucose is converted into glucose-6-phosphate?
glucose-1-phosphate is converted (reversibly) to glucose-6-phosphate by the enzyme phosphoglucomutase. Those tissues also house the enzyme glucose-6-phosphatase, which converts glucose-6-phosphate into free glucose that is secreted into the blood, thereby restoring
blood glucose levels
to normal.
What happens when glucose-6-phosphate is absent during carbohydrate metabolism?
In GSDI, the absence of G6Pase activity leads to
the accumulation of G6P in the liver and consequently the accumulation of glycogen and lipids
, responsible for hepatomegaly and hepatic steatosis.
Why does Cori’s disease cause hypoglycemia?
The mutations cause
a deficiency of the enzyme liver phosphorylase kinase
. The disorder is characterized by slightly low blood sugar (hypoglycemia) during fasting. Excess amounts of glycogen are deposited in the liver, causing enlargement of the liver.
What enzyme is deficient in Cori’s disease?
Glycogen storage disease type III (GSD III) is an autosomal recessive metabolic disorder and inborn error of metabolism (specifically of carbohydrates) characterized by a deficiency in
glycogen debranching enzymes
. It is also known as Cori’s disease in honor of the 1947 Nobel laureates Carl Cori and Gerty Cori.
What diseases are caused by enzymes?
- Familial hypercholesterolemia.
- Gaucher disease.
- Hunter syndrome.
- Krabbe disease.
- Maple syrup urine disease.
- Metachromatic leukodystrophy.
- Mitochondrial encephalopathy, lactic acidosis, stroke-like episodes (MELAS)
- Niemann-Pick.
