Small group 1 - problem 5

Question 1

Identify the genetic enzyme deficiency that may be the cause of this child’s problems.

Answer 1

Type 1 glycogen storage disease, AKA von Gierke’s disease. The deficient enzyme is glucose-6-phosphatase in the liver, kidney, and intestinal mucosa

Question 2

What are the 2 forms of G6Pase deficiency

Answer 2

a deficiency in the enzyme or a deficiency in the transporter that brings glucose-6-phosphate into the ER.

Question 3

What is causing the enlarged abdomen?

Answer 3

Accumulation of glycogen and fat in the liver

Question 4

Gluconeogenesis is blocked because of G6Pase deficiency - true or false?

Answer 4

True

Question 5

Why can the patient not maintain normal blood glucose levels during short fasts

Answer 5

Because the patient cannot generate free glucose from either glycogen degradation or gluconeogenesis

Question 6

What are the clinical manifestations of G6Pase deficiency?

Answer 6

Growth retardation, enlarged liver, hypoglycemia, lactic acidemia, hyperuricemia, and hyperlipidemia

Question 7

What is the frequency of GSD1?

Answer 7

1 in 100,000 among newborns

Question 8

What are the nutritional therapies for this GSD?

Answer 8

Frequent meals, continuous nocturnal gastric infusion of glucose, and orally administered uncooked cornstarch

Question 9

What are the outcomes for a patient with GSD1 if they have early detection and treatment?

Answer 9

Normal growth, pubertal development, etc.

Question 10

What risk do children who grow normally with GSD1 still face?

Answer 10

liver adenomas and progressive renal disease as they age

Question 11

What are the consequences of untreated GSD1 on fasting glucose?

Answer 11

Hypoglycemia

Question 12

What are the consequences of untreated GSD1 on serum cholesterol and triglycerides

Answer 12

increased because of the increase in fatty acid metabolism and availability of the acetyl-CoA precursor

Question 13

What are the consequences of untreated GSD1 on fasting free fatty acids

Answer 13

Epinephrine release
(due to low glucose levels) will stimulate the mobilization of adipose tissue fatty acids to provide energy supplies for tissues, which can use them.

Question 14

What are the consequences of untreated GSD1 on blood uric acid

Answer 14

Some G6P will go through PPP, which would lead to a rise in ribose 5-phosphate formation, which will increase synthesis of purines, which break down into uric acid. So uric acid will increase.

Question 15

What are the consequences of untreated GSD1 on mental intelligence at age 3

Answer 15

Difficulty maintaining CNS function due to low glucose levels. 20% of patients also show neutropenia and neutrophil dysfunction in addition to intermittent severe infectious disease

Question 16

Which side of the ER does the catalytic subunit of G6Pase face?

Answer 16

Lumen

Question 17

What is the rate limiting step of the G6Pase?

Answer 17

Transport of G6P into the lumen

Question 18

What is a common feature of the defect with the G6P transporter?

Answer 18

neutropenia

Question 19

What is the main difference between the defect in the transporter and the defect in the enzyme?

Answer 19

The transporter is ubiquitously expressed throughout the body while the transporter is only found in gluconeogenic tissues.

Question 20

What is the significance of glycolysis to neutrophils?

Answer 20

anaerobic glycolysis is how they get their ATP

Question 21

What happens when neutrophils lack G6PD

Answer 21

They can’t produce glucose via gluconeogenesis, resulting in

1. enhanced neutrophil apoptosis
2. activation of the hypoxia-inducible factor
3. G6PT-deficient neutrophils exhibit enhanced oxidative stress and have elevated levels of ROS

Question 22

Why would a liver transplant help someone with this disease?

Answer 22

Liver is the major site of gluconeogenesis and contains most of the G6Pase in the body. Replacing the liver should restore normal glucose homeostasis and metabolic function.