Flashcards in Inborn Errors 1 & 2: Hypoglycemia and Disorders of Fat Utilization Deck (31):
How can you differentiate defects in gluconeogenesis and fatty acid breakdown?
Both present with hypoglycemia upon fasting, but defects in gluconeogenesis will present with ketones while defects in fatty acid breakdown will not.
What is the "Whipple's triad" definition of hypoglycemia?
Autonomic activation: sweating, shaking, tachycardia, anxiety, weakness, hunger
Neuroglycopenic symptoms: irritable, resltess, headache, confusion, visual changes, slurred speech, behavior changes, somnolense, coma
BG less than 50 mg/dL Resolution with ingestion of glucose
Where does blood glucose come from fasting by hour?
0 - 4 hours after eating: absorption
4 - 14 hours after eating: glycogenolysis
10 - 18 hours after eating: gluconeogenesis
12 - ... hours after eating: fatty acid oxidation
When glucose can't get out of the liver, what other pathway can it take?
It can be converted to triglycerides (which show up as high serum triglycerides).
Von Gierke disease typically presents _______ hours into fasting.
Two other chemical products are produced in those with glucose 6-phosphatase deficiency: _____________.
uric acid (because the ribose monophosphate shunt creates purines) and lactic acid (because of the backing up of gluconeogenesis)
Von Gierke is a glycogen synthesis disorder type ____.
Those with glucose 6-phosphatase deficiency require what treatments?
Constant glucose (to avoid any gluconeogenesis)
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 _______________.
defects in aldolase B which is responsible for splitting fructose into two 3-carbon units
The mitochondrial form of HMG co-a synthase participates in __________- while 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 one cause of congenital hyperinsulinemia?
If a woman has hyperglycemia while pregnant, then the baby will make more insulin. When the baby leaves the mother's uterus, the glucose is gone but the insulin remains high – leading to hypoglycemia after birth.
What are two causes of congenital hyperinsulinemia?
If a woman has hyperglycemia while pregnant, then the baby will make more insulin (because maternal insulin does not cross the placenta). When the baby leaves the mother's uterus, the glucose is gone but the insulin remains high – leading to hypoglycemia after birth.
Another cause is a defect in the potassium channels that regulate insulin secretion. If they are congenitally blocked, then insulin will be secreted continuously.
Midline defects and poor growth are indicative of ___________.
ACTH or GH deficiency
What does plethoric mean?
What is ketotic hypoglycemia?
A diagnosis of exclusion in which a person (often a child) is hypoglycemic and ketotic without an identifiable cause, often occurring after an illness. Fortunately, ketosis usually precedes hypoglycemia, thus giving a chance to catch the illness before it develops to dangerous hypoglycemia.
The classic quartet of lab values seen in Von Gierke disease is _____________.
hypertriglyceridemia, lactic acidosis, hyperuricemia, and hypoglycemia
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.
Why does fructose intolerance lead to hypoglycemia while fasting?
Because accumulation of fructose 1-phosphate (one of the initial intermediates in fructose metabolism) leads to inhibition of glycogenolysis
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?
How can you definitively tell between MCAD and CPT deficiencies?
MCAD deficiencies will present with elevated acylcarnitines, while CPT deficiencies will prevent with elevated carnitines.
Why does ethanol ingestion lead to lactic acidosis?
Because 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?
High protein diet – this being branching enzyme deficiency
Why do those with branching deficiency present with hypotonia?
Because 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 _____________.
later hypoglycemia and lactic acidosis, because glycogen can sustain the body's needs for a little while and the gluconeogenesis pathway gets backed up