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Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

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Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)
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Page 1: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Glycogen storage diseases

Dr. Samah Kotb 2015

Cellular Biochemistry and

Metabolism2(CLS 333)

Page 2: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

GLYCOGEN STORAGE DISEASES

CHAPTER 6

Page 3: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Glycogen

Page 4: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals and fungi. The polysaccharide structure represents the main storage form of glucose in the body.

Page 5: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Disorders of glycogen metabolism

Page 6: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Disorders of glycogen metabolism

• The most common disease in which glycogen metabolism becomes abnormal is diabetes, in which, because of abnormal amounts of insulin, liver glycogen can be

abnormally accumulated or depleted. Restoration of normal glucose metabolism usually normalizes glycogen

metabolism, as well.

Page 7: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• In hypoglycemia caused by excessive insulin, liver glycogen levels are high, but the high insulin levels prevent the glycogenolysis necessary to maintain normal blood sugar levels. Glucagon is a common treatment for this type of hypoglycemia.

Page 8: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Various inborn errors of metabolism are caused by deficiencies of enzymes necessary for glycogen synthesis or breakdown. These are collectively referred to as glycogen storage diseases .

Page 9: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Glycogen depletion endurance exercise

Page 10: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Long-distance athletes, such as marathon runners, cross-country skiers, and cyclists, often experience glycogen depletion, where almost all

of the athlete's glycogen stores are depleted after long periods of exertion without enough

energy consumption. This phenomenon is referred to as hitting the wall.

Page 11: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Glycogen depletion can be forestalled in three possible ways.

Page 12: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

First, during exercise, carbohydrates with the highest possible rate of conversion to blood glucose (high glycemic index) are ingested continuously. The best possible outcome of this strategy replaces about 35% of glucose consumed at heart rates above about 80% of maximum.

Page 13: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• The glycemic index is a number associated with a particular type  of  carbohydrate-containing  food  that  indicates  the food's effect on a person's blood glucose (also called blood sugar  ) level.

Page 14: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Second, through endurance training adaptations and specialized regimens (e.g. fasted low-intensity endurance training), the body can condition type I muscle fibers to improve both fuel use efficiency and workload capacity to increase the percentage of fatty acids used as fuel, sparing carbohydrate use from all sources.

Page 15: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Third, by consuming large quantities of carbohydrates after depleting glycogen stores as a result of exercise or diet, the body can increase storage capacity of intramuscular glycogen stores. This process is known as carbohydrate loading.

Page 16: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• When experiencing glycogen debt, athletes often experience extreme fatigue to the point that it is difficult to move. As a reference, the best professional cyclists in the world will usually finish a 4 to 5 hr stage race right at the limit of glycogen depletion using the first three strategies.

Page 17: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• When athletes ingest both carbohydrate and caffeine following exhaustive exercise, their

glycogen is replenished more rapidly

Page 18: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Glycogen storage diseases

Page 19: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Glycogen storage diseases (GSDs) are a group of inherited genetic disorders. They cause glycogen to be improperly formed or released in the body. This results in a build up of abnormal amounts or types of glycogen in tissues.

Page 20: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• The main types of GSDs are categorized by number and name and include:

Page 21: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Type I (Von Gierke disease, defect in glucose-6-phosphatase) most common type of GSD; accounts for 90% of all GSD cases.

• Type II (Pompe’s disease, acid maltase deficiency).

• Type III (Cori’s disease, debrancher enzyme deficiency)

Page 22: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Type IV (Andersen’s disease, brancher enzyme deficiency).

• Type V (McArdle’s disease, muscle glycogen phosphorylase deficiency).

• Type VI (Hers’ disease, liver glycogen phosphorylase deficiency).

Page 23: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Type VII (Tarui’s disease, muscle phosphofructokinase deficiency).

• Type IX (liver glycogen phosphorylase kinase deficiency).

Page 24: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Glycogen is mainly stored in the liver or muscle tissue. As a result, GSDs usually affect functioning of the liver, the muscles, or both.

• Liver: The GSDs that mainly affect the liver are types I, III, IV, VI, and IX.

Page 25: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Muscles: The GSDs that mainly affect muscles are types V and VII.

• Type II affects nearly all organs including the heart.

Page 26: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Causes

Page 27: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Causes

1) GSDs are caused by a genetic enzyme defect. It is inherited from both parents.

Page 28: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

2) Normally, enzymes help convert glucose into glycogen for storage. Other enzymes convert the glycogen back to glucose when energy is needed. This happens during activity like exercise. With GSD, some of these enzymes are defective, deficient, or absent.

Page 29: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• The abnormal glycogen build up in the liver and/or muscle tissues.

Page 30: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

The main risk factor for GSDs is having a family member with this disease. The risk varies with the type of GSD.

Risk Factors

Page 31: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Parents with one child with GSD have a 25% of having another child with GSD. In a few of the GSD types, the risk rises to 50%. In this case only male children are affected.

Page 32: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Symptoms

• The most common symptoms of GSDs include:

* Low blood sugar.* Enlarged liver.* Slow growth.* Muscle cramps.

Page 33: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Signs and symptoms of specific types of GSDs include:

Page 34: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Type I:• 1) Large and fatty liver and kidneys.• 2) Low blood sugar.• 3) High levels of lactate, fats, and uric acid in the blood• 4) Impaired growth and delayed puberty.• 5) Osteoporosis.• 6) Increased mouth ulcers and infection.

Page 35: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Type II:• 1) Enlarged liver and heart.• 2) In severe cases, muscle weakness and heart

problems develop.• 3) In severe cases, infants may suffer fatal heart failure

by the age of 18 months.• 4) Milder forms of type II may not cause heart

problems.

Page 36: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)
Page 37: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Type III:• 1) Swollen abdomen due to an enlarged liver.• 2) Growth delay during childhood.• 3) Low blood sugar.• 4) Elevated fat levels in blood.• 5) Possible muscle weakness.

Page 38: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Type IV:• 1) Growth delay in childhood.• 2)Enlarged liver Progressive cirrhosis of the liver

(which may lead to liver failure). • 3) May affect muscles and heart in late-onset type.

Page 39: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Type V:• 1) Muscle cramps during exercise.• 2) Extreme fatigue after exercise.• 3) Burgundy-colored urine after exercise.

Page 40: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Type VI, IX:• 1) Liver enlargement occurs, but diminishes with age.• 2) Low blood sugar.

Page 41: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Type VII:• 1) Muscle cramps with exercise.• 2) Anemia.

Page 42: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Diagnosis

Page 43: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• The doctor will ask about symptoms and medical history. A physical examination will be done. Diagnosis of GSDs usually occurs in infancy or childhood. It is often done by the symptoms listed above.

Page 44: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Tests may include

• Biopsy of the affected organs. • Blood and urine samples.• MRI (Magnetic Resonance Imaging) scan: a test that

uses magnetic waves to make pictures of the inside of the body.

Page 45: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Treatment

Page 46: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Treatment

Treatment will depend on the type of GSD and the symptoms. Your doctor will develop a plan based on your specific symptoms.

Page 47: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Treatment of GSDs that affect the liver

Page 48: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• These general guidelines apply to people with types I, III, IV, VI, and IX.

Page 49: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• The goal of treatment is to maintain normal blood glucose levels. This may be done with:

• Nasogastric infusion of glucose for infants and children under age two.

Page 50: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Dietary changes, including: • Children over age two frequent small carbohydrate

feedings throughout the day; may include uncooked cornstarch (provides a steady slow-release form of glucose)

Page 51: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• Type I only elimination of foods that are high in fructose or lactose.

• Allopurinol (Aloprim, Zyloprim) reduces uric acid levels in the blood to prevent gout and kidney stones.

Page 52: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Type IV sometimes treated with liver transplantation.

Page 53: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Treatment of GSDs That Affect the Muscles

Page 54: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• These general guidelines apply to people with types V and VII:

• The goal of treatment is to avoid muscle fatigue and/or cramps induced by exercise. This is done by:

Page 55: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• 1) Regulating or limiting strenuous exercise to avoid fatigue symptoms.

Page 56: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

2) Improving exercise tolerance by oral intake of glucose or fructose (fructose must be avoided in people with type I), or an injection of glucagon.

Page 57: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• 3) Eating a high protein diet.

Page 58: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

Prevention

Page 59: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• There is no way to prevent GSDs. However, early treatment can help control the disease once a person has it.

Page 60: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

• If you have a GSD or a family history of the disorder, you may want to consult a genetic counselor. They can help determine the risk for your children.

Page 61: Glycogen storage diseases Dr. Samah Kotb 2015 Cellular Biochemistry and Metabolism2 (CLS 333)

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