Glycogen storage disorders and glycogenolysis

Question 1

Type 1 GSD is aka?

Answer 1

Von Gierke disease

Question 2

What enzyme is deficient in GSD Type I?

Answer 2

Glucose-6-phosphatase.

Question 3

What are the main symptoms of GSD Type I?

Answer 3

Severe hypoglycemia, hepatomegaly, lactic acidosis, hyperuricemia, hyperlipidemia.

Question 4

What is the treatment for GSD Type I?

Answer 4

Frequent oral glucose or cornstarch, allopurinol for hyperuricemia, and management of hyperlipidemia
Fructose and galactose restriction

Question 5

GSD type II is aka?

Answer 5

Pompe’s disease

Question 6

What enzyme is deficient in GSD Type II?

Answer 6

Acid alpha-glucosidase (also known as acid maltase).

Question 7

What are the key features of GSD Type II?

Answer 7

Progressive muscle weakness, cardiomegaly, respiratory failure, and hypotonia.
Muscle biopsy shows vacuoles

Question 8

How is GSD Type II treated?

Answer 8

Enzyme replacement therapy (ERT) with alglucosidase alfa/ Myozyme

Question 9

Type III GSD aka?

Answer 9

COri/ Forbes disease
Limit dextrinosis

Question 10

What enzyme is deficient in GSD Type III?

Answer 10

Debranching enzyme (glucan-branching enzyme).

Question 11

What are the clinical features of GSD Type III?

Answer 11

Fasting Hypoglycemia, hepatomegaly (d/t accumulation of branched chain polysaccharide), growth retardation

Question 12

What is the treatment for GSD Type III?

Answer 12

Frequent feeding with cornstarch and management of muscle symptoms.

Question 13

GSD type IV is aka

Answer 13

Andersen disease

Question 14

What enzyme is deficient in GSD Type IV?

Answer 14

Branching enzyme (glycogen branching enzyme).

Question 15

What are the major clinical features of GSD Type IV?

Answer 15

Progressive liver failure, cirrhosis, hepatomegaly d/t accumulation of polysaccharides with few branch points, muscle weakness, and early death (usually in childhood).

Question 16

What is the treatment for GSD Type IV?

Answer 16

Liver transplant is often required due to the severity of liver involvement.

Question 17

GSD type V is aka

Answer 17

McArdle disease

Question 18

What enzyme is deficient in GSD Type V?

Answer 18

Muscle glycogen phosphorylase.

Question 19

What is the clinical manifestation of GSD Type V?

Answer 19

Exercise induced Muscle cramps, exercise intolerance, myoglobinuria and rhabdomyolysis leading to renal failure and muscle weakness after exercise.

Second wind phenomenon

Question 20

Second wind phenomenon

Answer 20

Sudden improvement in exercise capacity after initial weakness

Question 21

How is GSD Type V managed?

Answer 21

Avoidance of strenuous exercise, a high-protein diet, and glucose supplementation before exercise.

Question 22

GSD type VI aka

Answer 22

Hers disease

Question 23

What enzyme is deficient in GSD Type VI?

Answer 23

Hepatic glycogen phosphorylase.

Question 24

What are the symptoms of GSD Type VI?

Answer 24

Hepatomegaly, mild hypoglycemia, and normal growth and development (usually no severe complications).

Question 25

How is GSD Type VI treated?

Answer 25

Diet management with glucose or cornstarch to prevent hypoglycemia.

Question 26

GSD type VII is aka

Answer 26

Tarui disease

Question 27

What enzyme is deficient in GSD Type VII?

Answer 27

Muscle phosphofructokinase.

Question 28

What are the symptoms of GSD Type VII?

Answer 28

Similar to McArdle disease (Type V), including muscle cramps, exercise intolerance, and myoglobinuria, but with more severe involvement of the muscles. Hemolytic anemia Growth retardation

Question 29

How is GSD Type VII treated?

Answer 29

High-protein diet and glucose supplementation before exercise.

Question 30

What enzyme is deficient in GSD Type 0?

Answer 30

Glycogen synthase.

Question 31

What are the symptoms of GSD Type 0?

Answer 31

Hypoglycemia, early death

Question 32

What is the difference between early-onset and late-onset Pompe disease?

Answer 32

Early-onset Pompe disease- in infants with severe hypotonia, cardiomegaly, and respiratory failure. Late-onset Pompe disease- in childhood or adulthood with progressive muscle weakness and respiratory problems, but without heart involvement.

Question 33

GSD type XI is aka?

Answer 33

Fanconi Bickel Syndrome

Question 34

What enzyme is deficient in GSD Type XI?

Answer 34

Glucose transporter 2 (GLUT2).

Question 35

What are the clinical features of GSD Type XI?

Answer 35

Hepatomegaly, renal tubular dysfunction, rickets, and growth retardation.

Question 36

What is glycogenolysis?

Answer 36

The breakdown of glycogen into glucose-1-phosphate and free glucose to maintain blood glucose levels.

Question 37

What is the rate-limiting enzyme of glycogenolysis?

Answer 37

Glycogen phosphorylase (requires Vitamin B6 as a cofactor).

Question 38

Name the key enzymes of glycogenolysis.

Answer 38

Glycogen phosphorylase – breaks α(1→4) bonds. Debranching enzyme – removes α(1→6) branches. Phosphoglucomutase – converts G1P → G6P. Glucose-6-phosphatase (only in liver) – converts G6P → free glucose.

Question 39

What hormones regulate glycogenolysis?

Answer 39

Stimulated by: Glucagon (liver) and Epinephrine (muscle & liver). Inhibited by: Insulin.

Question 40

How does glucagon activate glycogenolysis?

Answer 40

Glucagon → cAMP → PKA activation → Phosphorylates glycogen phosphorylase → Glycogen breakdown.

Question 41

How does glycogenolysis differ in the liver and muscle?

Answer 41

Liver: Releases free glucose into the blood (has glucose-6-phosphatase). Muscle: Uses G6P for glycolysis (lacks glucose-6-phosphatase).

Question 42

Why is UDP-glucose important in glycogenesis?

Answer 42

It is the activated form of glucose that acts as a donor for glycogen synthesis.

Question 43

What is the rate-limiting enzyme of glycogenesis?

Answer 43

Glycogen synthase – adds glucose units via α(1→4) bonds.

Question 44

Glycogen storage disorders associated with liver cirrhosis

Answer 44

III, IV, IX

Question 45

Glycogen storage disorders associated with renal dysfunction

Answer 45

Type I, V

Question 46

Glycogen storage disorders associated with neurological involvement

Answer 46

Type II GSD

Question 47

GSD that are also lysosomal storage disease

Answer 47

1. Pompe's disease 2. Danon disease (type IIb)

Question 48

Complications of Von Gierke disease

Answer 48

PCO Hepatic adenoma Osteopenia Renal failure Pancreatitis Pulm HTN

Question 49

Von Gierke's and Pompe's disease inheritance

Answer 49

AR

Question 50

Adolescent male Calf muscle pain Excess glycogen buildup in muscles

Answer 50

McArdle disease Muscle glycogen phosphorylase deficiency

Question 51

In Anderson disease, there is accumulation of abnormal structure of glycogen called

Answer 51

Polyglucosan