NBME 24 Gluconeogenesis (NBME Answers)

NBME 24 Answers

nbme24/Block 3/Question#24 (reveal difficulty score)
A 3-month-old boy is brought to the emergency ...
Gluconeogenesis 🔍 / 📺 / 🌳 / 📖
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+24 upvote downvote
submitted by ∗tea-cats-biscuits(273)

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The disease here is fructose bisphosphatase deficiency. In it, IV glycerol or fructose doesn’t help because both enter the gluconeogenesis pathway below fructose bisphophatase. Galactose on the other hand enters above it. I don’t think you really need to know this to choose the correct answer since the clinical picture of fasting hypoglycemia that is corrected w/ some sort of sugar that can enter the gluconeogenesis pathway should clue you into the right answer.

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neonem I don't think you could have *totally* ruled out the other answers - I picked glycogen breakdown because it sounded kind of like Von Gierke disease (glucose-6-phosphatase) to me: characterized by fasting hypoglycemia, lactic acidosis, and hepatomegaly since you're not able to get that final step of exporting glucose into the blood. However, I guess in this case you wouldn't see that problem of glycerol/fructose infusion not increasing blood glucose. Nice catch. +27

vshummy I think you were super smart to catch Von Gierke! Just to refine your answer b/c I had to look this up after reading your explanation, von gierke has a problem with gluconeogenesis as well as glycogenolysis. So they’d have a problem with glycerol and fructose but also galactose since they all feed into gluconeogenesis before glucose-6-phosphatase. Great thought process! +24

drmomo glycerol and fructose both enter the pathway thru DHAP and glyceraldehyde-3-ph. Galactose enters thru Gal-1-ph to glu-1-ph conversion +3

linwanrun1357 In this cause (fructose bisphosphatase deficiency.,),fructose should help to increase serum glucose, bcz it can become into glucose-6-P by hexokinase. Therefore, this question makes me confused.... +

krewfoo99 According to uworld, fructose infusion will not increase blood glucose levels in Von Gierkes Disease as well +

atbangura I believe Von Gierke is not a plausible answer choice because a galactose infusion would still not see an elevation in glucose levels. Remember, galactose could be converted to galactose 6 phosphate, but in order to complete gluconeogenesis and allow glucose to leave the Liver for an increase of its concentration in the blood, the patient would still need glucose 6 phosphatase which is eliminated in Von Gierke. +2

lilyo So what disease is this??? I mean couldnt we have just answered the question based on the fact that the patient responds to galactose being infused and we know that galactose feeds into gluconeogenesis?? I am so confused. +1

djtallahassee Its Hereditary Fructose intolerance right? gets sick after fructose and I guess glycerol can jump in via aldolase B on this pathway via page 74 of FA2019. It looked like a fructose thing to me so I just marked out the other ones and moved on. +1

paperbackwriter @djtallahassee I was wondering same, but hereditary fructose intolerance also results in inhibition of glycogenolysis :/ confusing question. +

amt12d A much simpler way to think about this, without trying to figure out a diagnosis, I looked at the time frame for when the child was presenting. He has eaten poorly for 3 days, by now, his glycogen breakdown is gone. His body would be trying to make glucose, therefore, gluconeogenesis is impaired, not glycogen breakdown. +7

tyrionwill if fructose kinase is not available (fructose intolerence), then some fructose may go to F-6-P by hexokinase, then goes to G6P if gluconeogenesis is needed. however this patient's fructose kinase was intact, so no fructose would have go to F6P, so there would be no blood glucose increment after injection of fructose. +1

shayokay You had to know that fructose and glycerol enter glycolysis at DHAP/G3P, and galactose enters glycolysis at G6P (gal-> gal-1-p -> glu-1-p -> glu-6-p). This means that one of the 3 enzymes between G6P and DHAP/G3P is not functioning properly. Most likely this would be fructose-1,6-bisphosphatase because there does not appear to be anything wrong with glycolysis. "Fructose-1,6-bisphosphatase (FBP1) deficiency is characterized by episodic acute crises of lactic acidosis and ketotic hypoglycemia, manifesting as hyperventilation, apneic spells, seizures, and/or coma. Acute crises are most common in early childhood; nearly half of affected children have hypoglycemia in the neonatal period (especially the first 4 days) resulting from deficient glycogen stores. Factors known to trigger episodes include fever, fasting, decreased oral intake, vomiting, infections, and ingestion of large amounts of fructose." https://www.ncbi.nlm.nih.gov/books/NBK550349/ +1

shayokay Also, even though Von Gierke is categorized as a glycogen storage disease it is really a problem with gluconeogenesis not glycogen breakdown. So even if you thought this was VG, you still could have gotten the right answer. In VG, any monosaccharide other than glucose (fructose, galactose, glycerol, etc.) will not raise the plasma glucose level because they all require gluconeogenesis to be converted into glucose and this cannot happen because there is no glucose-6-phosphatase. This is why the treatment for VG is frequent oral glucose in the form of cornstarch and avoidance of fructose and galactose. +

+5 upvote downvote
submitted by ∗usmle11a(102)

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guys VG would worsen with galactose infusion, remebmber they dont have G6Pase which means they cant convert anything to glucose

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tyrionwill Yes, VG makes the liver into muscle, where all sugars (except glucose) can only be burned to lactate+glycerol(from glycolysis), ATP (from TCA metabolism, to give uric acid), and fat deposit (from glycerol+pyruvate going to FA+TG) to worsen the situation. Sugar cannot be made into glucose in liver for other tissues. +

+1 upvote downvote
submitted by ∗cassdawg(1780)

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My dumb ass thought ketonemia was like anemia of ketones or something and thus meant low ketones so I almost put fatty acid oxidation (hypoketotic hypoglycemia). FYI ketonemia is high ketones.

Defects in fatty acid oxidation would also be corrected with the sugar additions so even if you suck at medical vocab you could rule it out.

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j44n if it was glycolysis they wouldnt be able to metabolize the galactose either, a defect in glycogen breakdown/glycogenolysis would't effect the immediate metabolism of a monosacharide it would effect the long term storage of it. I don't think we were supposed to know what disease this is I think we were just supposed to think about the metabolism of the three sugars in question. Hexokinase only converts fructose when it is extremely overloaded with fructose(it has a low affinity for it... they'll never say that so lets say "high Km"). Glycogen synthesis happens over time and he had poor feeding for 3 days so his glycogen would already be gone and he would be immediately symptomatic the second his blood glucose dropped +

+0 upvote downvote
submitted by ∗adong(144)

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I also had no idea what the diagnosis was and purely went off elimination: Can't be fatty acid oxidation bc of the ketonemia, which you wouldn't be able to produce if that was the defect. Glycogen breakdown/synthesis are related to glycogen storage diseases, which the presentation didn't line up well with. Also I was thinking of a pathway that would incorporate glycerol, fructose and galactose which seemed more in line with gluconeogenesis/glycolysis. Between the last two, I went with faulty gluconeogenesis bc that would elad to his hypoglycemia. I don't know how legit or applicable that is to other questions, but thought I'd at least share in case anyone finds it helpful.

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