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Retired NBME 20 Answers

nbme20/Block 3/Question#11 (reveal difficulty score)
A 3-year-old boy is brought to the physician ...
Heterozygous mutation in the ankyrin gene ๐Ÿ” / ๐Ÿ“บ / ๐ŸŒณ / ๐Ÿ“–
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 +14  upvote downvote
submitted by โˆ—nala_ula(127)
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The histology is of spherocytes (small spherical cells w/o central pallor). Hereditary spherocytosis is due to defect in proteins interacting with RBC membrane skeleton and plasma membrane (ankyrin, band 3, protein 4.2, spectrin). Mostly autosomal dominant inheritance (so heterozygous mutation since you only need one mutant allele to get the disease).

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wuagbe  To add to this: homozygous HS presents with hemolysis even in absence of stressors. this patient is only presenting with pale skin, and there are no schistocytes on the peripheral smear, so it's a heterozygous ankyrin mutation. +9
pg32  I wanted to pick hereditary spherocytosis but the mean corpuscular concentration was normal and I thought it was supposed to be elevated? Also, why are there so many RBCs that are way bigger than the spherocytes? +8
nephroguy  I'm assuming that the MCC is normal because the patient is heterozygous for HS. Not sure if this is correct, but that was my thought process +1
draykid  Are there any papers that explain the difference in expression of homozygous vs heterozygous HS? +25
waterloo  I don't know if that matters as much, like the phenotype difference of homozygous or heterozygous for this question. Since you only need one allele to show this, play odds. Is he more likely to have AA or Aa. That was my thought process. Also if you see spherocytes you'd be going for ankyrin right, not B-globin bc that should be target cells - regardless of MCHC. +1
alimd  as I remember AD are always heterzygous. Because homozygous are always lethal. +5



 +4  upvote downvote
submitted by xw1984(8)
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I got this Q wrong. I was wondering why this patient โ€œhas no personal or family historyโ€. Hereditary spherocytosis should be a AD disease, so, generally speaking, this diz should be seen in each generation, right?

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step1soon  I was thinking the same! +
wuagbe  Several genetics questions on NBME20 appear to be trying to throw us off by changing the descriptions of inheritance, leaving us to assume incomplete penetrance, smh. +



 +3  upvote downvote
submitted by โˆ—dr_jan_itor(87)
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Can anyone answer why this one can't be F. Beta thalasemia major? I was thinking becaues of his anemia and the "european descent" which includes the mediteranian europeans. Unless NMBE writers think that european only means the ones with extra white people lol

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dickass  European implies northern european (they even specified the patient was a person of pallor), mediterranean descent is usually implied by country of origin or by straight-out writing 'mediterranean'. +
poisonivy  The MCV is normal, thalassemias are microcytic anemias, that hint helps to rule out the thalassemias. However, I got it wrong, not sure why it cannot be a homozygous mutation in the ankyrin gene +2
adong  @poisonivy, other commenter pointed out it's autosomal dominant so best answer would be heterozygous +



 +2  upvote downvote
submitted by โˆ—victor_abdullatif(10)
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I think the key to this question is to use elimination for facts that we know for sure. The first is that it's a normocytic anemia, so all thalassemias are rule out since thal = microcytic.

That leaves A and D. Since the MCHC is normal (which is not what we would expect for hereditary spherocytosis) and the patient's symptoms are severe, they must have a "milder" version of the disease (e.g. achondroplasia is also autosomal dominant and is lethal if you get the homozygous form).

Obviously some big leaps in reasoning here but that's one path to the right answer

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victor_abdullatif  edit #1: made a typo. meant to say "the patient's symptoms are NOT severe" sorry about that! +
l0ud_minority  Yes I don't understand why the MCHC is normal that is still not what is expected. I wish NBME provided answer keys and cited their sources for their rationale. +



 +1  upvote downvote
submitted by sciguy(1)
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HS is autosomal dominant, but exhibits incomplete penetrance. So he had no record of personal family, but still likely heterzygous.

(Wikipedia) The clinical severity of HS varies from symptom-free carrier to severe hemolysis because the disorder exhibits incomplete penetrance in its expression.

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ibestalkinyo  This is what threw me off; I figured with 2 unaffected parents, it's more likely he had an autosomal recessive mutation. +1



 +0  upvote downvote
submitted by โˆ—strugglebus(189)
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Auto dom disease are usually heterozygous (or so they want us to assume)

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xxabi  How do you know is autosomal dominant? +3
scpomp  Hereditary spherocytosis +1
fshowon  Isnt the mean corpuscular hemoglobin concentration increased in spherocytosis? Thats what through me off. +5
charcot_bouchard  yes, would be inc in prev NBME. But this is batshit nbme 20. U have to identify spherocytes without central pallor in PBF +4
charcot_bouchard  yes, would be inc in prev NBME. But this is batshit nbme 20. U have to identify spherocytes without central pallor in PBF +



 +0  upvote downvote
submitted by โˆ—sunnyside(2)
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Can anyone justify why they did not describe an increased MCHC? FA 2019 says spherocytosis has high MCHC, and they did not even have it on the upper end of normal.

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