Unit 2 Abali Lecture 7 Glycogen Storage Diseases

Question 1

What is a glycogen storage disease?

Answer 1

When glycogen is not stored properly, macromolecules accumulate in the cells and cause cell death

Question 2

Glycogen storage diseases and the liver

Answer 2

liver is unable to breakdown glycogen, which leads to hypoglycemia (low blood sugar)

Question 3

Glycogen storage disease and the muscles

Answer 3

weakness, exercise fatigue, heart failure

Question 4

What type of disease is glycogen storage diseases?

Answer 4

autosomal recessive

Question 5

Schiff test

Answer 5

stains glycogen on liver biopsy, which tells us if the person has a glycogen storage disease or not

Question 6

Name the 7 glycogen storage diseases

Answer 6

von Gierke
Pompe
Cori
McArdle
Hers Disease
Tarui disease
Glucose 6 phosphate dehydrogenase deficiency

Question 7

Enzyme for von Girke

Answer 7

deficiency of glucose 6 phosphatase

Question 8

2 types of von girke

Answer 8

T1: Deficiency in glucose 6 phosphatase, Enzyme that Converts glucose 6 phosphate to glucose in the liver

T2: Type 2: deficient in glucose 6 phosphatase translocase, which transfers G6P from cytosol to the ER

Question 9

Dangers of von girke (explain the chemical mechanism)

Answer 9

Liver cant convert G6P to glucose, so G6 Phosphate builds up in the liver

Very badly impaired gluconeogenesis and glycogenolysis

The muscles are forced to break down glycogen for energy instead

Lactate in the blood is converted to glucose via the Cori cycle in gluconeogenesis, which does not happen since glucose 6 phosphatase is missing. This leads to lactic acidosis

Question 10

Clinical Aspects of Von Gierke (symptoms)

Answer 10

Shows up in infancy

Poor growth, impaired limbs, doll like face, hepatomegaly (enlarged liver)

Hypoglycemia

Acidosis

Acidosis and hypoglycemia combined can lead to severe intellectual disability

Question 11

Other symptoms of Von Girke

Answer 11

High cholesterol due to poor liver function → Causes pancreatitis

Kidney enlargement due to glycogen backup

High uric acid → gout → joint pain

Liver cancer due to hepatic adenomas

Question 12

Treatment von girke

Answer 12

uncooked corn starch throughout day and night

Avoid lactose, fructose and sucrose because they can cause G6 Phosphate to accumulate

Allopurinol: gout

Bicarbonate: acidosis

ACE (angiotensin-converting enzyme): kidney dysfunction

Fibrates: high triglycerides

Question 13

Von Girke and the Cori cycle

Answer 13

Liver uptake of lactate and its conversion to glucose

Glucose → lactate → glucose

Key to remember: the liver starts producing crazy amounts of lactate!

Lactate produced by the liver CANNOT be converted to glucose

CORI CYCLE DOES NOT WORK!

Question 14

Pompe disease enzyme

Answer 14

lysosomal alpha 1,4-glucosidase

Question 15

Pompe disease mechanism

Answer 15

Lysosomal storage disease, glycogen accumulates in lysosomes

Lack of alpha 1,4 glucosidase leads to accumulation of glycogen

Question 16

Symptoms of pompe

Answer 16

Symptoms in infancy: macroglossia (enlarged tongue), weakness, hypotonia (low muscle tone),

hypertrophic cardiomyopathy

The liver is still enlarged due to fluid build up caused by heart failure

Creatine kinase elevation (shows muscle damage)

Lack of alpha glucosidase via genetic testing

Question 17

Treatment for pompe disease

Answer 17

Test for elevated levels of creatine kinase

Enzyme replacement therapy and gene therapy is the only hope

Most kids die at 1yrs old due to heart failure

Question 18

Cori disease enzyme

Answer 18

Deficiency in debranching enzyme: alpha 1,6 glucosidase

Question 19

Cori disease mechanism

Answer 19

Very similar to von Girke, just milder

Less severe hypoglycemia because gluconeogenesis still works!

Cori cycle still works! So lactate can be converted to glucose!

Debranching enzyme is importance for the muscle, so cori disease can lead to muscle and heart damage 🙁

Question 20

Treatment - cori

Answer 20

High glucose and high protein

No need to avoid lactose, sucrose or fructose because G6P accumulation is not a concern

Question 21

McArdle Disease enzyme

Answer 21

MYOPHOSPHORYLASE –>required to continue glycogen break down even after debranching

Question 22

Clinical aspects and symptoms - McArdle

Answer 22

Report muscle cramps

Dark urine due to break down of myoglobin (muscle break down causes high amounts of myoglobin to show up in the blood)

Surprisingly, they feel fatigued the first 10 minutes of exercise, but then perk up due to vasodilation
(SECOND WIND)

Adolescence or young adulthood

Question 23

Treatment - McArdle

Answer 23

Enzyme assay and gene analysis

Reproduce second wind by 15 min cycle test

ischemic forearm exercise test: which was developed by Dr McArdle himself.

During this test, a blood pressure cuff is placed on a patient doing forearm exercises (opening and closing the fist) and blood is drawn. In someone with McArdle disease, there would be no increase in lactate.

Patients should carb up and not do strenuous exercise

Question 24

Hers disease enzyme

Answer 24

Lack of hepatic glycogen phosphorylase

Question 25

Treatment of Hers Disease

Answer 25

Very mild glycogen storage diseases

Long fasts are not recommended

Slow release carbs recommended (i.e. uncooked starch)

Question 26

Hers disease symptoms

Answer 26

a swollen abdomen due to an enlarged liver

a history of poor growth or short stature
frequent feeding - always hungry, episodes of low blood sugar (hypoglycaemia) on fasting

excessive tiredness following activity.

Question 27

Tarui Disease enzyme

Answer 27

Muscle phosphofructokinase deficiency

Question 28

Tarui disease mechanism

Answer 28

Muscle cannot convert glycogen into glucose for energy

Question 29

Tarui symptoms

Answer 29

Fatigue
Exercise intolerance
Muscle pain

Question 30

Avoid strenuous exercise
High protein diet

Answer 30

Avoid strenuous exercise
High protein diet