🔸 Inborn Errors 1 & 2: Hypoglycemia and Disorders of Fat Utilization

Question 1

How can you differentiate defects in gluconeogenesis and fatty acid breakdown?

Answer 1

Both present with hypoglycemia if fasting. Defects in gluconeogenesis presents with ketones. Defects in fatty acid breakdown does not have ketones.

Question 2

What is “MCAD” deficiency?

Answer 2

Medium-chain acyl-CoA dehydrogenase

(MCAD)-deficiency.

Question 3

Where does blood glucose come from ( when fasting) by hour?

Answer 3

0 - 4 hrs: absorption
4 - 14 hrs: glycogenolysis
10 - 18 hrs: gluconeogenesis
12+ hrs: fatty acid oxidation

Question 4

When glucose can’t get out of the liver, what other pathway can it take?

Answer 4

It can be converted to triglycerides

will show up as high serum triglycerides

Question 5

Von Gierke disease typically presents […] hours into fasting.

Answer 5

4-6

Question 6

Two other chemical products are produced in those with glucose 6-phosphatase deficiency: […].

Answer 6

• uric acid (b/c the ribose monophosphate shunt creates purines) and
• lactic acid (b/c gluconeogenesis is backed up)

Question 7

Von Gierke is a glycogen synthesis disorder type […].

Answer 7

1

Question 8

Those with glucose 6-phosphatase deficiency require what treatments?

Answer 8

Constant glucose (to avoid any gluconeogenesis)
Drip feeding
Cornstarch (which is slow release carbohydrate)

Question 9

What is the classic presentation of glycogen storage defect (GSD 0)?

Answer 9

Hyperglycemia after a meal followed by hypoglycemia, lactic acidosis, and ketotic acidosis

No liver enlargement.

Question 10

[…] leads to cirrhosis that typically requires liver transplant by age 4-6.

Answer 10

Branching enzyme defect (GSD IV)

Question 11

Hereditary fructose intolerance results from defect in […] which is responsible for…[…].

Answer 11

•aldolase B ; splitting fructose into two 3-carbon units

Question 12

The mitochondrial form of HMG co-a synthase participates in […]
The cytosolic form participates in […].

Answer 12

ketone formation;

cholesterol synthesis

Question 13

Increased serum acylcarnitines, abnormal urinary organic acids, and increased serum acyl co-a are indicative of ___________.

Answer 13

MCAD deficiency (medium-chain acyl co-a dehydrogenase deficiency)

Question 14

What is a non-inherited cause of congenital hyperinsulinemia?

Answer 14

If mom has hyperglycemia while pregnant, the baby will make more insulin. After birth, the glucose is gone but the insulin remains high. This results in hypoglycemia after birth.

Question 15

What channel defect can cause congenital hyperinsulinemia?

Answer 15

A defect in potassium channels regulating insulin secretion.
If these are congenitally blocked, insulin will be secreted continuously.

Question 16

Midline defects and poor growth are indicative of […] or […] deficiency.

Answer 16

ACTH or GH deficiency

Question 17

What does plethoric mean?

Answer 17

Red-faced

Question 18

What is ketotic hypoglycemia?

Note: ‘often’ occurs in a child.

Answer 18

• A diagnosis of exclusion in which a person is hypoglycemic and ketotic without an identifiable cause, often occurring after an illness.
• Ketosis usually precedes hypoglycemia, thus a chance to catch the illness before it develops to dangerous hypoglycemia.

Question 19

What is the classic quartet of lab values seen in Von Gierke disease.

Answer 19

hypoglycemia
hypertriglyceridemia,
lactic acidosis,
hyperuricemia,

Question 20

Why do those who can’t make glycogen have ketotic acidosis?

Answer 20

Because insulin will be low and counter-regulatory hormones high (after a meal)

Question 21

Adults with phosphorylase deficiency can typically fast for up to […] hours.

Answer 21

18

Question 22

Why does fructose intolerance lead to hypoglycemia while fasting?

Answer 22

•accumulation of fructose 1-phosphate leads to inhibition of glycogenolysis
(F1P is an initial intermediate in fructose metabolism)

Question 23

A patient develops jaundice and neurologic symptoms after ingestion of milk. What enzyme are they lacking?

Answer 23

Galactose 1-phosphate uritidyltransferase (GALT)

Question 24

A patient becomes hypoglycemic 15 hours into fasting. He does not have an enlarged liver, and blood labs indicate no ketones. What enzyme is he likely missing?

Answer 24

•MCAD

Medium-chain acyl-CoA dehydrogenase deficiency

Question 25

How can you definitively tell between MCAD and CPT deficiencies?

Answer 25

• MCAD→ present with elevated acylcarnitines,

* CPT→ present with elevated carnitines.

Question 26

Why does ethanol ingestion lead to lactic acidosis?

Answer 26

ethanol metabolism creates NAD+, and the pyruvate to lactate conversion regenerates NADH.

Question 27

How should you manage the glycogen synthase disorder that presents without liver enlargement?

Answer 27

• this is a branching enzyme deficiency

* treat with High protein diet

Question 28

Why do those with branching deficiency present with hypotonia?

Answer 28

the remnants of undigested glycogen branch points destroys the muscle

Question 29

What labs can help you distinguish between glucose 6-phosphatase deficiency and debranching enzyme deficiency?

Answer 29

Debranching enzyme deficiency presents with hypoglycemia later, and there will not be elevated lactate or uric acid
(as there is in glucose 6-phosphatase deficiency)

Question 30

Fructose 1,6-bisphosphatase deficiency presents with […].

Answer 30

late hypoglycemia and lactic acidosis,

glycogen can sustain the body’s needs for a little while and the gluconeogenesis pathway gets backed up

Question 31

Hereditary fructose intolerance damages what two organs?

Answer 31

Liver and kidney

Question 32

aldolase B is responsible for splitting […] into 3-carbon units.

Answer 32

fructose

Question 33

What is the “Whipple’s triad” definition of hypoglycemia?

Answer 33

Autonomic activation: sweating, shaking, tachycardia, anxiety, weakness, hunger

Neuroglycopenic symptoms: irritable, restless, headache, confusion, visual changes, slurred speech, behavior changes, somnolense, coma

BG less than 50 mg/dL Resolution with ingestion of glucose