THE USMLE TIMES - #89
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Welcome to issue #89 of The USMLE Times… This is the 89th straight week we’ve posted our USMLE Times Newsletter! Thank you to all of our supporters—new and old!
I’m Paul Ciurysek, MD, and this is The USMLE Times: An independent, subscriber-supported newsletter designed to help you survive medical school, pass your USMLE exams, and match into your dream residency program.
Here’s what’s on tap for issue #89 of the USMLE Times:
Question of the Week (Biochemistry/Genetics)
This week’s video training (Life-Changing Advice For Med Students)
Question deep-dive & breakdown
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Let’s dive in!
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A 4-year-old male presents to his pediatrician with a persistent productive cough, recurrent abdominal pain, and malodorous diarrhea. The child and his family have recently migrated from Eastern Europe. The child's medical history reveals no past medical visits, and he has not received any vaccinations. On examination, the child's height and weight are at the 20th percentile. The cough is productive of non-bloody green sputum, and chest auscultation reveals the presence of diffuse wheezing. Vital signs include a temperature of 98.9°F, pulse of 90/minute, respiratory rate of 18/minute, and blood pressure of 100/70 mmHg. The sweat chloride test results reveal a chloride value of 90 mmol/L. Which of the following is likely to be revealed by further investigation?
A) Protein misfolding
B) Alterations in dystrophin protein structure
C) Intramitochondrial accumulation of iron
D) Non-functional peroxisomes
E) Elevated parathyroid hormone
The answer & question breakdown is at the bottom of the post.
🔗 LINKS TO RECENT POSTS
USMLE Times Issue #88 - READ HERE
USMLE Times Issue #87 - READ HERE
USMLE Times Issue #86 - READ HERE
ANSWER + QUESTION BREAKDOWN
The Mental Model for this week’s question:
Step 1. Identify the question’s goal (Identify the correct finding based on further investigation).
Step 2. Read the vignette and identify the diagnosis.
Step 3. Since there are many potential answer choices (ie. It is not a singular possible response), look to the answer choices and identify one linked to your diagnosis.
Step 4. Double-check the other choices to ensure you’ve selected the only viable option.
GENERAL ANALYSIS
This question describes a 4-year-old male presenting with symptoms suggestive of cystic fibrosis, including a persistent productive cough, recurrent abdominal pain, and malodorous diarrhea. The positive sweat chloride test confirms the diagnosis. The question asks which abnormality is likely to be found in this condition.
ANSWER CHOICES:
ANSWER CHOICE A: Protein misfolding
Protein misfolding can occur in several genetic disorders where the protein does not fold into its functional conformation.
ANSWER CHOICE B: Alterations in dystrophin protein structure
Dystrophin is a protein associated with muscular dystrophies, such as Duchenne and Becker muscular dystrophy.
ANSWER CHOICE C: Intramitochondrial accumulation of iron
This is characteristic of diseases like Friedreich's ataxia, which involve mitochondrial dysfunction.
ANSWER CHOICE D: Non-functional peroxisomes
Non-functional peroxisomes are involved in disorders like Zellweger syndrome, which affect lipid metabolism.
ANSWER CHOICE E: Elevated parathyroid hormone
Elevated parathyroid hormone is seen in conditions like hyperparathyroidism, affecting calcium metabolism.
THE VERDICT…
Cystic fibrosis is an autosomal recessive disorder caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. The most common mutation, ΔF508, leads to the misfolding of the CFTR protein. This misfolded protein is recognized by the cell's quality control mechanisms and is targeted for degradation by the proteasome, preventing it from reaching the cell surface.
As a result, chloride ions cannot be properly transported across epithelial cell membranes, leading to thick, viscous secretions in the lungs, pancreas, and other organs.
This results in the clinical manifestations of cystic fibrosis, such as chronic respiratory infections, pancreatic insufficiency, and malabsorption, which are consistent with the symptoms described in the vignette.
FINAL ANSWER: A: Protein misfolding
That’s it for issue #89 of The USMLE Times!
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