Glycogen Storage Diseases

Glycogen Storage Diseases: Inheritance and MOA

- Inheritance: Mostly Autosomal Recessive

- MOA: Defective breakdown of glycogen

Glycogen Storage Diseases: What happens in liver and muscle?

- Liver: Hypoglycemia: Unable to break down glycogen → low blood sugar

- Muscle: Also cannot breakdown glycogen → weakness

Von Gierke's Disease: MOA

- Deficiency in glucose-6-phosphatase

(Cannot convert G6P → Glucose)

Von Gierke's Disease: Presentation and Symptoms

- Presents: In infancy (2-6 months)

- Symptoms: Severe hypoglycemia between meals, lethargy, seizures, lactic acidosis, hepatomegaly

Why is muscle weakness not a symptom of Von Gierke's Disease?

- Because the liver uses glucose-6-phosphatase, not muscle. Meaning muscle can use G6P for glycolysis → no weakness

Von Gierke's Disease: Dx

- DNA testing

- Liver Biopsy

Von Gierke's Disease: Tx

- Cornstarch

- Avoid: Sucrose, Lactose, Fructose, Galactose

Pompe's Disease: MOA

- Acid α-glucosidase deficiency in lysosomes → accumulation of glycogen in lysosomes

Pompe's Disease: Presentation and Prognosis

- Presentation: In infancy

- Symptoms: Cardiomegaly, enlarged tongue**, hypotonia, hepatomegaly

- Prognosis: Severe disease → often death in infancy/childhood from heart failure

Cori Disease (Type III): MOA

- Defective deb ranching enzyme → hard for muscle/liver to mobilize glycogen into glucose

Cori's Disease: Presentation

- Milder hypoglycemia

- No lactic acidosis

- Gluconeogenesis is intact

- Muscles are hypertonic and weak**

McArdle's Disease: Deficiency and MOA

- Muscle glycogen phosphorylase deficiency

- Glycogen not properly broken down in muscle cells

McArdle's Disease: Presentation

- Adolescence/early childhood

- Symptoms: Exercise intolerance, fatigue, cramps, muscle swelling

*Urine turns dark after exercise

Glycogen Synthase Deficiency: MOA

- Deficiency means glycogen cannot be synthesized → build up of blood [glucose]

Glycogen Synthase Deficiency: Presentation

- After carb meal: ↑ Blood [Glucose], lactate, & lipids

- Fasting: ↓ Glucose and ↑ Ketone bodies

- Defect in muscle tissue causes weakness and difficulty with exercise

Glycogen Synthase Deficiency: Tx

- Frequent complex carb meals

- Meals high in protein

Anderson Glycogen Storage Disease: MOA

- Abnormal branching enzyme → dysfunctional glycogen storage

Anderson Glycogen Storage Disease: Presentation

- Abnormal glycogen structure in liver leads to cirrhosis/liver failure

- Hypotonia and muscle weakness common