Metabolism Disorder

Question 1

Glycogen storage disease (GSD)

Answer 1

G-6-P deficiency (GSD I)

Question 2

G-6-P Deficiency General

Answer 2

• Most severe GSD

* Glucose can’t leave liver after gluconeogenesis

Question 3

G-6-P Deficiency Complication

Answer 3

• Enlarged liver
• Increased lactate production => lactic acidosis
• increased fatty acid synthesis => hyper-TGs and hyper-cholesterol
• increased uric acid
• short stature, doll-like face

Question 4

G-6-P Deficiency Presentation

Answer 4

• Early in life

* Severe fasting hypoglycemia within 3-4 hours after meal

Question 5

G-6-P Deficiency Tx

Answer 5

Constant supply oral glucose avoid hypoglycemia

Question 6

Glycogen synthesis disorder (2)

Answer 6

1. Hepatic Glycogen Synthase Deficiency (GSD 0)

2. Branching Enzyme Deficiency (GSD IV)

Question 7

Hepatic Glycogen Synthase Deficiency (GSD 0) general

Answer 7

• Cannot make glycogen

=> rely gluconeogenesis for glucose production

Question 8

Hepatic Glycogen Synthase Deficiency (GSD 0) presentation

Answer 8

• Hyperglycemia after meal
• Fasting hypoglycemia
• Increased lactate
• Severe ketotic hypoglycemia
• NO liver enlargement!!

Question 9

Hypoglycemia Symptoms

Answer 9

1. ANS: (due to epineprhine?)
   * Sweating
   * Tachy
   * Weakness
   * Anxiety
2. Neuroglycopenic symptom:
   * Headache
   * Confusion
   * Slurred speeh
   * Visual change
   * Behaviour change

Question 10

Hypoglycemia within 4 - 6 hours fasting (4)

Answer 10

1. G-6-P Deficiency
2. Hyperinsulinism
3. Cortisol and Growth Hormone deficiency infants

Question 11

Hepatic Glycogen Synthase Deficiency (GSD 0) Tx

Answer 11

• high protein diet => provide gluconeogenesis substrate

* low GI complex carbs => minimize post-prandial hyperglycemia & hyperlactacidemia

Question 12

Branching Enzyme Deficiency (GSD IV) general

Answer 12

Abnormal glycogen (not branched) accumulate in liver and skeletal muscle

Question 13

Branching Enzyme Deficiency (GSD IV) complications (4)

Answer 13

1. Progressive liver cirrhosis => transplant by 4-6 yrs
   * Hepatosplenomegaly
2. Cardiomyopathy
3. Muscle weakness, hypotonia
4. Neuropathy

Question 14

Glycogen Breakdown Disorders (3)

Answer 14

1. Phosphorylase Deficiency (GSD VI)
2. Phosphorylase Kinase deficiency (GSD IX)
3. Debranching Enzyme deficiency (GSD III)

Question 15

Phosphorylase Deficiency (GSD VI), and
Phosphorylase Kinase deficiency (GSD IX)

Answer 15

Normal: 
* gluconeogenesis
* lipolysis
* fatty acid oxidation
* ketogenesis
=> milder than G6PD

Question 16

Phosphorylase Deficiency (GSD VI), and
Phosphorylase Kinase deficiency (GSD IX) presentation

Answer 16

1. Hepatomegaly
2. Short stature
3. Mild muscle weakness
4. Adult fast for 18-24 hours

Question 17

Phosphorylase Deficiency (GSD VI), and
Phosphorylase Kinase deficiency (GSD IX) Tx

Answer 17

Raw cornstarch

Question 18

Debranching enzyme deficiency (GSD III)

Answer 18

Defective enzyme => accumulation abnormal glycogen in liver and muscle

Question 19

Debranching enzyme deficiency (GSD III) presentation

Answer 19

Normal:
* lactate
* uric acid
Abnormal:
* hepatomegaly
* hypoglycemia
* myopathy
* short starture
* increase ketones

Question 20

Debranching enzyme deficiency (GSD III) Tx

Answer 20

• continuous glucose, raw cornstarch => prevent hypoglycemia

* high protein diet => help myopathy and growth failure

Question 21

Gluconeogenic disorder (1)

Answer 21

Fructose-1,6-bisphosphatase deficiency

Question 22

F-1,6-BPase deficiency

Answer 22

Inability to generate glucose via gluconeogenesis

Question 23

F-1,6-BPase deficiency presentation

Answer 23

• Late hypoglycemia: after 18-24 hours fasting
• NO enlarged liver!
• Severe lactic acidosis => hyperventilation
• Increase pyruvate
• Increase ketonic hypoglycemia

Question 24

Hereditary Fructose Intolerance

Answer 24

• Aldolase defect => accumulation F1P => inhibit glycogenolysis and glyconeogenesis

Question 25

Hereditary Fructose Intolerance presentation

Answer 25

* Symptoms with intro fructose (fruit) in diet => n/v, coma * Elevated LFTs

Question 26

F-1,6-BPase deficiency Tx

Answer 26

1. Acute: give glucose => will correct lactate