USMLE PRACTICE QUESTION #90
TOPIC: Biochemistry/Genetics
Today’s question will test your understanding of a commonly tested Biochemistry/Genetics condition.
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A 19-year-old male presents to the clinic with tremors, difficulty speaking, and difficulty walking. The physician noted greenish-brown rings in the patient’s eyes during the physical examination. Blood tests reveal elevated liver transaminases and decreased ceruloplasmin levels. A liver biopsy is performed, and results show increased hepatic copper content. Which of the following is best described as this patient’s underlying genetic defect?
A) Dysregulation of metal-responsive transcription factor 1 (MTF1) leading to reduced metallothionein synthesis
B) Aberrant interaction between ATP7A and ATP7B leading to impaired copper transport
C) Defective ATP7B protein causing impaired copper transport and excretion
D) Mutation in the SLC31A1 gene leading to decreased intestinal copper absorption
E) Disrupted function of the CTR1 copper transporter causing excess cellular copper uptake
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
The MENTAL MODEL used to answer this question comes from our detailed test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:
Step 1. Read the last line to get to the heart of the question: “Which of the following is best described as this patient’s underlying genetic defect?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Diagnose the problem, and 2nd: Identify the defect responsible for the disease.
Step 3: Read the vignette carefully and ask yourself: “What’s the underlying defect responsible for this patient’s condition?”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
The 19-year-old male presents with tremors, difficulty speaking, difficulty walking, and greenish-brown rings in the eyes (likely Kayser-Fleischer rings), along with elevated liver transaminases, decreased ceruloplasmin levels, and increased hepatic copper content. These findings are classic for Wilson disease, a genetic disorder of copper metabolism.
ANSWER CHOICES:
CHOICE A: Dysregulation of metal-responsive transcription factor 1 (MTF1) leading to reduced metallothionein synthesis
Explanation: MTF1 regulates the expression of metallothioneins, which bind metals like zinc and copper. MTF1 dysregulation is not the primary defect in Wilson disease.
CHOICE B: Aberrant interaction between ATP7A and ATP7B leading to impaired copper transport
Explanation: ATP7A is involved in copper transport in tissues outside the liver, while ATP7B regulates hepatic copper excretion. Wilson disease is specifically due to defects in ATP7B, not a combined dysfunction of ATP7A and ATP7B.
CHOICE C: Defective ATP7B protein causing impaired copper transport and excretion
Explanation: Wilson disease is caused by mutations in the ATP7B gene, which encodes a copper-transporting ATPase. This protein is essential for incorporating copper into ceruloplasmin and excreting excess copper into bile.
CHOICE D: Mutation in the SLC31A1 gene leading to decreased intestinal copper absorption
Explanation: The SLC31A1 gene encodes a copper transporter involved in intestinal absorption of copper. Decreased intestinal absorption of copper would lead to low body copper levels, not the excess seen in Wilson disease.
CHOICE E: Disrupted function of the CTR1 copper transporter causing excess cellular copper uptake
Explanation: CTR1 is involved in cellular uptake of copper. While CTR1 is important for cellular copper uptake, Wilson disease results from defective excretion of excess copper due to mutations in ATP7B, not from increased cellular uptake via CTR1.
FINAL VERDICT…
In Wilson disease, defective ATP7B leads to impaired copper transport, resulting in the accumulation of copper in the liver, brain (especially the basal ganglia), corneas (Kayser-Fleischer rings), and other tissues. This causes both hepatic and neurological symptoms. The patient’s neurological symptoms (tremors, difficulty speaking, and walking), along with hepatic dysfunction (elevated liver enzymes) and low ceruloplasmin levels, are hallmark features of Wilson disease.
CORRECT ANSWER: C) Defective ATP7B protein causing impaired copper transport and excretion
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That’s it for question 90!
See ya tomorrow 👋