NBME 23 α-Thalassemia trait (NBME Answers)

NBME 23 Answers

nbme23/Block 1/Question#33 (reveal difficulty score)
A 25-year-old woman and her 25-year-old ...
α-Thalassemia trait 🔍 / 📺 / 🌳 / 📖
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+12 upvote downvote
submitted by mambabambaboom(12)

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bc the parents are asian, they are cis deletion carriers. So their kid can either be a cis carrier or have Hb Barts, its not possible to get HbH

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+9 upvote downvote
submitted by ∗asapdoc(79)

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Dr.Goljan explains it really well on the audio. I will just give the basic idea. All the hemoglobins have alpha in it therefore you cannot notice it on hemoglobin electrophoresis

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someduck3 Just to add to this; a-thal is due to a deletion. While b-thal is due to a mutation. If they had a b-thal there would be target cells. a-thal just presents as microcytic & hypochromic. +10

almondbreeze looks like a-thal can have target cells too. Individuals with alpha thalassemia trait (-α/-α or --/αα) are asymptomatic, with a normal CBC. The peripheral blood smear typically shows hypochromia, microcytosis, and target cells. (emedicine.medscape.com › article › 955496-clinical) +

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submitted by ∗drschmoctor(137)

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Both parents have alpha-thalassemia trait. Given they are Asian, they will have the cis-mutation. That is, each parent will have 1 chromosome 17 with 0 alpha chain genes + another chromosome 17 with 2 alpha chain genes).

Thus, each parent can pass on either 0 or 2 copies of the alpha chain gene. So, the offspring will have a

25% chance of having 0 alpha chains (causing hydrops fetalis & death in utero),
50% chance of having 2 alpha chains (alpha-thal trait, answer choice D), and a
25% chance of having 4 alpha chains (normal).

A) Hemoglobin H is when there is 1 alpha chain, so that is not possible.

B, C, D) Both parents had normal hemoglobin electrophoresis, so Hb S, HbSC, and B-thal are not possible.

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rockodude *alpha chain is on chromosome 16, beta chain is on chromosome 11 +1

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submitted by ∗nwinkelmann(366)

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I found a picture showing the transmission by two heterozygous alpha thalassemia trait asian (cis-deletion) parents, and modified it to also show the inheritance by two heterozygous alpha thalassemia african (trans-deletion) parents. Here you go: https://drive.google.com/open?id=1HQU1VuhI4Jc9WJR2POwnTq9T8wEdv7dw

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makinallkindzofgainz broken link +1

drdoom broken link +

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submitted by ∗masonkingcobra(408)

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http://sickle.bwh.harvard.edu/thal_inheritance.html

Easy pictures to understand

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+2 upvote downvote
submitted by ∗nor16(70)

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in ß Thalassemia there is HbA2 increase and HbA decreases, even in ß+ , normal electrophoresis rules this out. same for A)-C)

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tyrionwill Yes! The key point is the normal electrophoresis. Hemoglobin will not show any abnormalities until least one single allele of Hb fully develops mutation. alpha chain of Hb is contributed by two points within one single allele, while beta chain of Hb is made of only one point in one single allele, therefore: -- in alpha thalassemia Hb electrophoresis will be normal if only one point gets mutation, i.e., aa/a- which we call it the "minima type". If two points get mutation, i.e., cis aa/--, or trans a-/a-, the "minor type", the Hb electrophoresis will be either abnormal(Hb Barts 3-8%) or still normal. overall, we assume the parent both are the minima type, so their children have 50% chance to be the minor type, 25% to be fully normal, and 25% to be the trans minor. -- However in beta thalassemia, the mutation of one allele will lead to whole allele changed, so we just need the mutation once to generate an abnormal Hb electrophoresis result. +1

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submitted by ∗krewfoo99(115)

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In what situations will HbH be formed (3 alpha chain deletions)?

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ergogenic22 one parent has 2 deletions on the same gene, the other parent has 1 deletion, and the offspring receives all three. In this question, both parents have alpha 1 deletion +

ergogenic22 actually its possible that they both have 2 gene deletions, but regardless, a-thalassemia trait is more likely +

ergogenic22 and someone above said Asian people are cis-2 deletion so the offspring will not receive two deletion from one parent +

ergogenic22 ↑↑ I made a mistake by confusing trans and cis cis has deletions on the same chromosome and can pass two deletions to off spring, therefore a chance of allowing HbH +

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submitted by ∗prolific_pygophilic(17)

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Meme: Asian parents with a clear hemoglobinopathy, Me slapping the Alpha Thal Button

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submitted by ∗imgdoc(183)

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Just for completeness sake, I want to elaborate on HbH. THIS CAN LITERALLY ONLY HAPPEN if a Thalassemia minima, mated with a cis deletion-thalassemia minor patient. AKA Thalassemia MINIMA: a patient with only one alpha gene missing (from the normal 4 alpha genes present), mated with Thalassemia MINOR: two alpha genes with two absent alpha genes (CIS deletion ONLY).

This combo can produce HbH disease. Which presents with severe hypochromic microcytic anemia.

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