🔸 Inborn Errors 1 & 2: Hypoglycemia and Disorders of Fat Utilization Flashcards
How can you differentiate defects in gluconeogenesis and fatty acid breakdown?
Both present with hypoglycemia if fasting. Defects in gluconeogenesis presents with ketones. Defects in fatty acid breakdown does not have ketones.
What is “MCAD” deficiency?
Medium-chain acyl-CoA dehydrogenase
(MCAD)-deficiency.
Where does blood glucose come from ( when fasting) by hour?
0 - 4 hrs: absorption
4 - 14 hrs: glycogenolysis
10 - 18 hrs: gluconeogenesis
12+ hrs: fatty acid oxidation
When glucose can’t get out of the liver, what other pathway can it take?
It can be converted to triglycerides
will show up as high serum triglycerides
Von Gierke disease typically presents […] hours into fasting.
4-6
Two other chemical products are produced in those with glucose 6-phosphatase deficiency: […].
- uric acid (b/c the ribose monophosphate shunt creates purines) and
- lactic acid (b/c gluconeogenesis is backed up)
Von Gierke is a glycogen synthesis disorder type […].
1
Those with glucose 6-phosphatase deficiency require what treatments?
Constant glucose (to avoid any gluconeogenesis)
Drip feeding
Cornstarch (which is slow release carbohydrate)
What is the classic presentation of glycogen storage defect (GSD 0)?
Hyperglycemia after a meal followed by hypoglycemia, lactic acidosis, and ketotic acidosis
No liver enlargement.
[…] leads to cirrhosis that typically requires liver transplant by age 4-6.
Branching enzyme defect (GSD IV)
Hereditary fructose intolerance results from defect in […] which is responsible for…[…].
•aldolase B ; splitting fructose into two 3-carbon units
The mitochondrial form of HMG co-a synthase participates in […]
The cytosolic form participates in […].
ketone formation;
cholesterol synthesis
Increased serum acylcarnitines, abnormal urinary organic acids, and increased serum acyl co-a are indicative of ___________.
MCAD deficiency (medium-chain acyl co-a dehydrogenase deficiency)
What is a non-inherited cause of congenital hyperinsulinemia?
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.
What channel defect can cause congenital hyperinsulinemia?
A defect in potassium channels regulating insulin secretion.
If these are congenitally blocked, insulin will be secreted continuously.
Midline defects and poor growth are indicative of […] or […] deficiency.
ACTH or GH deficiency
What does plethoric mean?
Red-faced
What is ketotic hypoglycemia?
Note: ‘often’ occurs in a child.
- 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.
What is the classic quartet of lab values seen in Von Gierke disease.
hypoglycemia
hypertriglyceridemia,
lactic acidosis,
hyperuricemia,
Why do those who can’t make glycogen have ketotic acidosis?
Because insulin will be low and counter-regulatory hormones high (after a meal)
Adults with phosphorylase deficiency can typically fast for up to […] hours.
18
Why does fructose intolerance lead to hypoglycemia while fasting?
•accumulation of fructose 1-phosphate leads to inhibition of glycogenolysis
(F1P is an initial intermediate in fructose metabolism)
A patient develops jaundice and neurologic symptoms after ingestion of milk. What enzyme are they lacking?
Galactose 1-phosphate uritidyltransferase (GALT)
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?
•MCAD
Medium-chain acyl-CoA dehydrogenase deficiency
How can you definitively tell between MCAD and CPT deficiencies?
- MCAD→ present with elevated acylcarnitines,
* CPT→ present with elevated carnitines.
Why does ethanol ingestion lead to lactic acidosis?
ethanol metabolism creates NAD+, and the pyruvate to lactate conversion regenerates NADH.
How should you manage the glycogen synthase disorder that presents without liver enlargement?
- this is a branching enzyme deficiency
* treat with High protein diet
Why do those with branching deficiency present with hypotonia?
the remnants of undigested glycogen branch points destroys the muscle
What labs can help you distinguish between glucose 6-phosphatase deficiency and debranching enzyme deficiency?
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)
Fructose 1,6-bisphosphatase deficiency presents with […].
late hypoglycemia and lactic acidosis,
glycogen can sustain the body’s needs for a little while and the gluconeogenesis pathway gets backed up
Hereditary fructose intolerance damages what two organs?
Liver and kidney
aldolase B is responsible for splitting […] into 3-carbon units.
fructose
What is the “Whipple’s triad” definition of hypoglycemia?
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
