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Glycogen Storage Diseases
What is glycogen storage disease ?
The body’s cells need a steady supply of fuel in order to function the right way. This fuel is a simple sugar called glucose. Glucose comes from breaking down the food we eat. The body uses as much glucose as it needs to function and stores the rest to use later.
Before it can be stored, the body must combine the simple glucose units into a new, complex sugar called glycogen. The glycogen is then stored in the liver and muscle cells.
Glycogen storage disease (GSD) is a genetic condition in which the body has an enzyme problem and is not able to store or break down the complex sugar glycogen properly. GSD affects the liver, muscles and other areas of the body.
Types Of Glycogen Storage Disease
- Type I (von Gierke’s disease)
- Type Ia – Liver, kidneys, intestines
- Type Ib – Liver, kidneys, intestines, blood cells.
- Type II (Pompe’s disease)
- Type III (Forbes-Cori disease)
- Type IV (Andersen’s disease)
- Type V (McArdle’s disease).
- Type VI (Hers’ disease)
- Type VII (Tarui’s disease)
- Type VIII(Hepatic phosphorylase kinase deficiency)
- Type IX – Liver.
- Type XI (Fanconi-Bickel syndrome)
- The liver forms of GSDs (type I, III, IV and VI) are due to an increase in liver glycogen and hypoglycemia, which is caused by the inability to convert glycogen to glucose.
- The muscle forms of GSDs (type II, IIIA, V and VII) have mild symptoms appearing during strenuous exercises owing to the inability to provide energy for muscle contraction.
Von Gierke's Disease Type I
- It is an inherited disorder caused by deficiencies of specific enzymes in the glycogen metabolism pathway.
- TYPE 1 GSD.
- It was first described by Von Gierke in 1929 who reported excessive hepatic and renal glycogen in the autopsy reports of 2 children.
- It comprises 2 major subtypes, GSD Ia and GSD Ib.[1] In GSD Ia, there is a deficiency of enzyme glucose-6-phosphatase (G6Pase) which cleaves glycogen to glucose.
Cause
- GSD 1b is caused by mutations in the G6PC gene on chromosome 17q21 that encodes for the G6Pase-a catalytic subunit.
- GSD Ib results from mutations in the SLC37A4 gene on chromosome 11q23.3.
Characteristcs
- Hypoglycaemia
- Lacticacidemia
- Ketosis
- Hyperlipemia
- The enzyme G6Pase is primarily expressed in the liver, kidney, and intestine.
- It has its active site on the luminal side of the endoplasmic reticulum (ER).
- Glucose-6-phosphate translocase is responsible for translocating Glucose6-phosphate (G6P) from the cytoplasm into the ER lumen.
Pompo's Disease Type II
- Also known as acid-maltase disease and glycogen storage disease II
- Is a rare genetic disorder that causes progressive weakness to the heart and skeletal muscles.
- It is caused by mutations in a gene that makes an enzyme called acid alpha-glucosidase (GAA), which the body uses to break down glycogen, a stored form of sugar used for energy.
- That is deficiency of lysosomal a-1,4 and a1,6glucosidase
- The enzyme performs its function in intracellular compartments called lysosomes, which function as cellular clearing houses.
- Accumulation of glycogen in lysosomes.
There are two forms of Pompe disease:
- Early onset (infantile form) is caused by the complete or near complete deficiency of enzyme.
- Symptoms begin in the first months of life
- with feeding problems
- poor weight gain
- trouble breathing
- muscle weakness
- enlarged heart
- floppiness,
- head lag
- enlarged tongues
- fatal
- Late onset (juvenile/adult) results from partial deficiency of enzyme
- Begin as early as the first decade of childhood or well into adulthood.
- Muscle weakness progresses to death from respiratory failure after several years.
- The heart is usually not involved.
Treatment
- Enzyme replacement
Cori's Disease Or Type III
- Mutations in the AGL or Amylo-1,6-Glucosidase deficiency gene,The AGL gene provides instructions for making the glycogen debranching enzyme. (debranching enzyme)
- Forbes’ disease, also called Cori’s disease, or glycogenosis type III, rare hereditary disease GSDIII is divided into types IIIa, IIIb, IIIc, and IIId, which are distinguished by their pattern of signs and symptoms.
- GSD types IIIa and IIIc mainly affect the liver and muscles, and GSD types IIIb and IIId typically affect only the liver
- Accumulation of characteristic branched polysaccharide
Characteristics
- low blood sugar (hypoglycemia)
- excess amounts of fats in the blood (hyperlipidemia)
- elevated blood levels of liver enzymes.
- an enlarged liver (hepatomegaly).
- Liver size usually returns to normal during adolescence, but some affected individuals develop chronic liver disease (cirrhosis) and liver failure later in life.
Deficiency of debranching enzyme.
Andersen's Disease Or Type IV
- Absence of branching enzyme
- Death due to cardiac failure
- Glycogen is not made properly and abnormal glycogen molecules accumulate in cells; most severely in cardiac and muscle cells.
- The severity of this disease varies on the amount of enzyme produced.
- GSD IV is autosomal recessive
- It is an extremely rare disorder caused by production of an abnormal form of unbranched glycogen in all tissue.
- Patients exhibit hepatosplenomegaly with ascites and liver failure.
- There is death from heart or liver failure before 5 years of age.
Types
- Fatal perinatal neuromuscular type
- Congenital muscular type
- Progressive hepatic type
- Non-progressive hepatic type
- Childhood neuromuscular type
Type V Or Mcardle's Disease
- Absence of muscle phosphorylase
- Diminished exercise tolerane
- Muscle have abnormally high glycogen content
- Characterized with muscle cramps after exercise.
- People with GSDV typically experience fatigue, muscle pain, and cramps during the first few minutes of exercise (exercise intolerance).
- Exercise such as weight lifting or jogging usually triggers these symptoms in affected individuals.
- The discomfort is generally alleviated with rest. If individuals rest after brief exercise and wait for their pain to go away, they can usually resume exercising with little or no discomfort (a characteristic phenomenon known as "second wind").
Type VI (Liver Phosphorylase Deficiency ) - Her's Disease
- It manifests as hepatomegaly caused by increased deposits of normal glycogen in the liver or in red or white blood cells.
- Deficiency of the liver enzyme glycogen phosphorylase, which governs the metabolic breakdown of glycogen to the simple sugar glucose, which can then be used to meet the body’s energy needs.
- The enzyme’s absence causes glycogen to accumulate, greatly enlarging the liver and producing moderate hypoglycemia (low blood sugar), since the release of glucose from storage in the liver is impaired.
- Other symptoms of the disease are a mild increase in the acidity of the blood and growth retardation.
- No other organs seem to be involved. Unlike some of the related glycogen storage diseases, Hers’ disease does not cause mental retardation or reduce the life span.
Type VII Or Taruis’ Disease
- Muscle and erythrocyte phosphofructokinase deficiency
- Patients have abnormal glycogen in muscle.
- Exercise intolerance
- Unresponsiveness to glucose administration and hemolysis (caused by decreased glycolysis in RBC).
