Glycogen Metabolism

Question 1

What are the two tissues primarily affected by Glycogen Storage Disease?

Answer 1

Muscle and Liver

Question 2

What is GSD Type I also known as?

Answer 2

Type I Glycogenosis, or Von Gierke’s Disease

Question 3

What is GSD Type I?

Answer 3

Deficiency of G6Pase

Question 4

Where is G6P normally found?

Answer 4

In the Endoplasmic Reticulum of the:

• The Hepatocytes and Biliary Epithelial cells of the Liver
• Enterocytes of Intestine
• Proximal convoluted tubule cells of the nephron Kidney

Question 5

What are the different types of GSD Type I, and what do they result in a defect of?

Answer 5

• Ia: Catalytic subunit
• Ib: G6P Transporter
• Ic: Inorganic Phosphate Transporter
• IaSP: Stabilising Protein

Question 6

What is the incidence of GSD Type I?

Answer 6

1/100,000 births

Question 7

Where is the G6Pase gene located?

Answer 7

Chromosome 17 (17q21)

Question 8

What are the symptoms of GSD Type I?

Answer 8

• Protruding Abdomen due to liver enlarged by increased deposition of glycogen
• Hypoglycaemia 2-4hr post-prandial
• Growth Failure

Question 9

What is normal glucose concentration and GSD Type I glucose concentration?

Answer 9

• 5-5.5 mM (Normal)

- 4 mM (GSDI)

Question 10

What are the biochemical characteristics of GSD Type I?

Answer 10

• Hypoglycaemia
• Hyperlacticacidemia
• Hyperlipidaemia
• Hyperuricemia

Question 11

Why do people with GSD type I experience hypoglycemia 2-4 hours after eating?

Answer 11

Blockage of last stop of glycogenolysis/gluconeogenesis means an inability to produce glucose in times of deprivation, leading to fall in blood glucose

Question 12

What other symptoms are associated with hypoglycaemia?

Answer 12

• Sweating
• Hunger
• Tremor
• Parasthesia
• Personality Change
• Fatigue
• Seizures
• Coma

Question 13

Why do people with GSD Type I experience hyperlacticacidemia?

Answer 13

Excess of G6P due to lack of G6Pase causes G6P to enter the glycolytic pathway and be converted to lactate

Question 14

What are the symptoms associated with hyperlipidaemia?

Answer 14

Development of xanthomas (fatty buildup under the skin in the knees elbows feet and hands)

Question 15

How does GSD Type I cause hyperlipidemia by increasing glycerol synthesis?

Answer 15

Increaed G6P means increased rate of glycolysis so increased rate of DHAP production, which is used in reactions to make glycerol

Question 16

How does GSD Type I cause hyperlipidemia by increasing fatty acid synthesis?

Answer 16

Increaed G6P means more pyruvate, which enters the krebs cycle, until citrate leaves the mitochondria, converts back to Acetyl CoA and then converted to Malonyl CoA which is part of fatty acid synthesis

Question 17

What are the two mechanisms by which GSD Type I causes Hyperuricemia?

Answer 17

• Increased Purine Synthesis,which are converted to xanthine, then uric acid
• Reduced uric acid removal from kidney due to lactate competing out uric acid from transporters for excretion

Question 18

What are the symptoms of Hyperuricaemia?

Answer 18

-Gout (urine crystals in synovia) of big toe, foot and ankle.

Question 19

How is GSD Type I treated?

Answer 19

• Frequent Meals, Nocturnal feeding through nasogastric tube
• Liver transplant if serious