L10 Glycogen Storage Diseases

Question 1

Which enzyme is deficient in von Gierke’s disease?

Answer 1

Glucose-6-phosphatase

Question 2

Which of the following is X-linked?

a) von Gierke’s disease
b) Cori’s disease
c) Phosphorylase kinase deficiency
d) Hers’ disease

Answer 2

c) Phosphorylase kinase deficiency

Question 3

Pompe’s disease is caused by a deficiency in which enzyme?

Answer 3

alpha-1,4-glucosidase

Question 4

Cori’s disease is caused by a deficiency in which enzyme?

Answer 4

Amylo-1,6-glucosidase (debranching enzyme)

Question 5

Andersen’s disease is caused by a deficiency in which enzyme?

Answer 5

Amylo-(1,4 to 1,6)-transglycosylase (branching enzyme)

Question 6

McArdle’s disease is caused by a deficiency in which enzyme?

Answer 6

Glycogen phosphorylase (in muscle)

Question 7

Hers’ disease is caused by a deficiency in which enzyme?

Answer 7

Glycogen phosphorylase (in liver)

Question 8

Tarui’s disease is caused by a deficiency in which enzyme?

Answer 8

Phosphofructokinase (PFK)

Question 9

X-linked phosphorylase kinase deficiency affects which tissue(s)?

Answer 9

Liver

There is another disorder which is general phosphorylase kinase deficiency in all organs.

Question 10

Which glycogen storage diseases result in altered glycogen structure?

Answer 10

Cori’s disease: outer chains missing or very short

Andersen’s disease: Very long, unbranched chains

Question 11

Which glycogen storage disease does not alter the structure of glycogen, but causes a deficiency?

Answer 11

Glycogen synthase deficiency.

Question 12

Describe type 1 glycogen storage disease.

Answer 12

Glucose-6-phosphatase deficiency (von Gierke’s disease)

G6Pase catalyses the release of the phosphate group, allowing glucose to be released from liver into blood stream.

This disease means glucose cannot be released (hypoglycaemia) and so G6P builds up in hepatocytes (hepatomegaly).

Question 13

What are the complications that arise from von Gierke’s disease (type 1 glycogen storage disease)?

Answer 13

Severe hypoglycaemia and severe hepatomegaly

Question 14

What treatments are required for patients with glucose-6-phosphatase deficiency?

What is the common name for this disease?

Answer 14

Treatment:
1. (a) Drug-induced inhibition of glucose uptake by liver

(b) continuous intra-gastric feeding overnight to maintain blood glucose
2. Liver transplantation
3. Surgical transposition of the portal vein (send glucose-rich blood straight to peripheral tissues instead of via liver)

Question 15

Which of the glycogen storage diseases is the most severe?

Answer 15

Type 2: alpha-1,4-glucosidase deficiency (Pompe’s disease).

Patients normally die within a year from cardio-respiratory failure.

Question 16

Describe Pompe’s disease

Answer 16

Type 2 glycogen storage disease: alpha-1,4-glucosidase deficiency (Pompe’s disease).

a-1,4-glucosidase breaks down glycogen within lysosomes to stop the lysosome getting too full and rupturing.

Deficiency means it isn’t there to stop the glycogen overfilling the lysosome and so it bursts and releases all of its nasty contents (toxins and enzymes) into the cell. Very bad.

Occurs in all tissues, but particularly damages muscle tissue.

Question 17

How is glycogen storage disease type 2 treated?

Answer 17

GSD type 2 (Pompe’s disease) is treated by enzyme replacement therapy, restoring a-1,4-glucosidase.

Question 18

Describe glycogen storage disease type 3

Answer 18

GSD type 3 (Cori’s disease).

Deficiency of amylo-1,6,glucosidase (debranching enzyme).

Glycogen has an abnormal structure and builds up in liver and muscle = muscle weakness and liver dysfunction.

Treated by high protein diet.

Question 19

What is the role of debranching enzyme?

Answer 19

During degradation, branches are removed from the glycogen by glycogen phosphorylase and transferase; they leave small ‘stubs’ which also need to be removed for complete degradation. This is done by debranching enzyme.

Question 20

Why is Cori’s disease treated with a high protein diet?

Answer 20

To counteract the losses of amino acids via gluconeogenesis.

Question 21

What is Anderson’s Disease?

Answer 21

Glycogen storage disease (type 4).

Deficiency of amylo-(1,4-1,6)-transglycosylase (glycogen branching enzyme)

Causes liver dysfunction, patients rarely survive beyond 4yo.

Question 22

Describe the glycogen molecules in a patient with type 4 glycogen storage disease.

Answer 22

(GSD type 4 = Anderson’s disease)

Glycogen is present in normal concentrations, but has abnormal structure.

Long unbranched chains that make it very insoluble.

Question 23

What is McArdle’s disease?

Answer 23

Glycogen storage disease (type 5)

Deficiency in muscular glycogen phosphorylase.

Affects muscle but not liver as they contain different isoenzymes of phosphorylase.

Question 24

McArdle’s disease affects

A) the liver
B) muscles
C) both A and B
D) neither A nor B

Answer 24

B) muscles

Both the muscle and liver contain phosphorylase, but glycogen storage disease type 5 (McArdle’s) only affects the isozyme found in muscles.

Question 25

Which glycogen storage disease is characterised by an absence of lactate in the blood? ``` A) Type 1 (von Gierke's) B) Type 2 (Pompe's) C) Type 3 (Cori's) D) Type 4 (Anderson's) E) Type 5 (McArdle's) ```

Answer 25

E) Type 5 (McArdle's) Lack of phosphorylase means cells cannot convert glycogen to glucose and then to lactate.

Question 26

True or false: McArdle's disease is associated with severed muscle cramps after exertion

Answer 26

True. McArdle's disease is not fatal and is quite harmless as long as strenuous exercise is avoided.

Question 27

In GSD type 5 (McArdle's), what causes muscle tissue to break down? What symptom does this lead to?

Answer 27

Lack of ATP leads to muscle breakdown. Muscle breakdown results in general muscle weakness.

Question 28

Her's disease affects A) the liver B) muscles C) both A and B D) neither A nor B

Answer 28

A) the liver Similar to type 5, glycogen is not broken down because of a lack of glycogen phosphorylase, but this time in the liver.

Question 29

Is Her's disease (GSD type 6) considered to be mild or severe?

Answer 29

Mild, compared with the symptom of other glycogen storage diseases

Question 30

What are the symptoms of Her's disease (GSD type 6)?

Answer 30

Hepatomegaly Mild hypoglycaemia Mild ketosis Retarded growth

Question 31

Why is hypoglycaemia a symptom of Her's disease?

Answer 31

Deficiency of liver phosphorylase means the liver cannot break down glycogen to raise blood glucose levels.

Question 32

Why is ketosis a symptom of Her's disease?

Answer 32

Non-functioning TCA cycle results in ketosis.

Question 33

What is Tarui's disease?

Answer 33

Glycogen storage disease type 7 - muscle phosphofructokinase deficiency. Deficiency in PFK disrupts glycolysis. Leads to build up of glucose-6-phosphate and fructose-6-phosphate.

Question 34

What are the symptoms of Tarui's disease?

Answer 34

Painful muscle cramps. PFK deficiency prevents glycolysis, limiting ATP production.

Question 35

Tarui's disease leads to a build up of what in the muscles?

Answer 35

Glycogen.

Question 36

Which glycogen storage disease is associated with an inability to activate an inactive enzyme?

Answer 36

Type 8: X-linked phosphorylase kinase deficiency A defective phosphorylase kinase cannot add a phosphate group to convert phosphorylase b (inactive) to phosphorylase a (active).

Question 37

True or false: The symptoms of Her's disease (type 6) and x-linked phosphorylase kinase deficiency (type 8) are very similar.

Answer 37

True. Her's disease is autosomal recessive, but type 8 is X-linked.

Question 38

What is SGD type 9?

Answer 38

Phosphorylase kinase deficiency (autosomal recessive) Defective gene that encodes for a phosphorylase kinase subunit results in a faulty enzyme.

Question 39

What is GSD type 0?

Answer 39

Liver glycogen synthase deficiency. The only glycogen disorder that results in too little glycogen, rather than too much.

Question 40

True or false: Liver glycogen synthase deficiency (type 0) is always asymptomatic?

Answer 40

False. Some sufferers are asymptomatic, but others suffer from hypoglycaemia after meals or at other times.

Question 41

Which glycogen disorders can affect all tissues?

Answer 41

Type 2, 3, 4, and 9

Question 42

True or false: All glycogen disorders are autosomal recessive?

Answer 42

False. While most are autosomal recessive, type 8 is X-linked.