USMLE PRACTICE QUESTION #109

TOPIC: Biochemistry/Pathology

Dec 18, 2024

In USMLE practice question #109, we’ll assess our understanding of a highly tested biochemistry disorder.

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A 3-day-old newborn presents to the emergency department with poor feeding, vomiting, lethargy. The infant has been irritable and displays signs of hypotonia with intermittent episodes of opisthotonus. Laboratory results reveal elevated plasma levels of branched-chain amino acids (BCAAs) and their corresponding ketoacids. Which of the following interventions is the most appropriate initial step in managing this patient’s condition?

A) Start thiamine supplementation and monitor BCAA levels
B) Initiate a diet low in leucine, isoleucine, and valine
C) Administer high-dose biotin to activate BCKAD complex
D) Provide phenylbutyrate to reduce ammonia levels
E) Prescribe riboflavin to enhance mitochondrial function

Detailed Breakdown of Answers + Correct Answer Below ⏬

ANSWER + QUESTION BREAKDOWN

It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our 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 interventions is the most appropriate initial step in managing this patient’s condition?”

Step 2: Is this a first-, second-, or third-order question?
Answer: 2n order. 1st: Diagnose the condition; 2nd: Identify the most appropriate initial step in management.

Step 3: Read the vignette carefully and ask yourself: “Based on my diagnosis, what should I do next?”

Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.

GENERAL ANALYSIS

This vignette describes a 3-day-old newborn presenting with poor feeding, vomiting, lethargy, hypotonia, and intermittent opisthotonus (a sign of severe neurological distress). The laboratory findings reveal elevated plasma levels of branched-chain amino acids (BCAAs) and their corresponding ketoacids, strongly suggesting a diagnosis of Maple Syrup Urine Disease (MSUD).

ANSWER CHOICES:

CHOICE A: Start thiamine supplementation and monitor BCAA levels

Explanation: Thiamine supplementation is used in thiamine-responsive MSUD, a rare variant of MSUD that responds to thiamine therapy. Thiamine acts as a cofactor for the BCKAD complex. While supplementation may be beneficial in some forms of MSUD (such as thiamine-responsive MSUD), this is not the initial or most appropriate step for managing classic MSUD.

CHOICE B: Initiate a diet low in leucine, isoleucine, and valine

Explanation: The primary treatment for MSUD involves restricting dietary intake of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine. This reduces the accumulation of toxic metabolites that cause neurological damage.

CHOICE C: Administer high-dose biotin to activate BCKAD complex

Explanation: Biotin is a cofactor for several carboxylase enzymes but does not play a role in activating the BCKAD complex.

CHOICE D: Provide phenylbutyrate to reduce ammonia levels

Explanation: Phenylbutyrate is used to treat urea cycle disorders by reducing ammonia levels. MSUD involves elevated levels of BCAAs rather than ammonia, meaning phenylbutyrate would not address the underlying metabolic defect in MSUD.

CHOICE E: Prescribe riboflavin to enhance mitochondrial function

Explanation: While riboflavin is used as a cofactor in various mitochondrial enzymes, it does not play a role in managing MSUD.

FINAL VERDICT…

The most appropriate initial step in managing this newborn with Maple Syrup Urine Disease (MSUD) is to initiate a diet low in leucine, isoleucine, and valine. This dietary intervention reduces the accumulation of toxic metabolites from branched-chain amino acids and prevents further neurological damage. Early diagnosis and prompt initiation of dietary therapy are crucial for improving clinical outcomes in patients with MSUD.

KEY CONCEPTS:

MSUD is characterized by elevated levels of BCAAs (leucine, isoleucine, and valine) due to a deficiency in the BCKAD complex.
Symptoms typically present in the neonatal period with poor feeding, vomiting, lethargy, hypotonia, and neurological signs like opisthotonus.
Early diagnosis and management are crucial to prevent irreversible neurological damage.
The mainstay of treatment involves dietary restriction of BCAAs to prevent further accumulation of toxic metabolites.

CORRECT ANSWER: A) Start thiamine supplementation and monitor BCAA levels