USMLE PRACTICE QUESTION #64
USMLE PRACTICE QUESTION #64
TOPIC: Biochemistry (Glycogen storage diseases)
Today’s question will test your understanding of glycogen storage diseases.
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A 6-month-old infant is brought to the pediatric clinic by her parents, who are concerned about her poor weight gain and recurrent episodes of hypoglycemia, especially after fasting. The infant appears lethargic and has an enlarged liver on physical examination. Blood tests reveal elevated liver transaminases and lactate levels. A urine sample shows the presence of a reducing substance. Which of the following best describes the underlying cause of this infant's condition?
A) Deficiency in fructose-1,6-bisphosphatase
B) Deficiency in galactose-1-phosphate uridylyltransferase
C) Deficiency in aldolase B
D) Deficiency in glycogen branching enzyme
E) Deficiency in glucose-6-phosphate dehydrogenase
F) Deficiency in phosphofructokinase-1
G) Deficiency in glucose-6-phosphatase
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. Here’s how to think through this question:
Step 1. Read the last line to determine what the question is asking: Identify the underlying cause of the patient’s condition.
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Make a diagnosis, 2nd: Identify the underlying cause.
Step 3: Read the vignette and make a diagnosis.
Step 4. Ask yourself: “What’s the missing enzyme?” associated with this condition.
Step 5. Look at the answer choices and select the option most closely resembling your thoughts from “Step 4” above.
GENERAL ANALYSIS
In this case, the clinical presentation and laboratory findings are consistent with a glycogen storage disease. This condition is characterized by hypoglycemia, lactic acidosis, hepatomegaly, and the presence of a reducing substance in the urine. The underlying cause is an enzyme deficiency. Your job is to make a diagnosis based on the given information and to identify the missing enzyme.
ANSWER CHOICES:
CHOICE A: Deficiency in fructose-1,6-bisphosphatase
Explanation: This deficiency leads to impaired gluconeogenesis, causing hypoglycemia and lactic acidosis, but it is not the classic presentation described here.
CHOICE B: Deficiency in galactose-1-phosphate uridylyltransferase
Explanation: This enzyme deficiency causes galactosemia, leading to cataracts, liver disease, and intellectual disability.
CHOICE C: Deficiency in aldolase B
Explanation: This deficiency causes hereditary fructose intolerance, leading to hypoglycemia and liver damage upon fructose ingestion.
CHOICE D: Deficiency in glycogen branching enzyme
Explanation: This causes Andersen's disease (Glycogen Storage Disease Type IV), leading to liver cirrhosis.
CHOICE E: Deficiency in glucose-6-phosphate dehydrogenase
Explanation: This deficiency leads to hemolytic anemia under oxidative stress.
CHOICE F: Deficiency in phosphofructokinase-1
Explanation: This enzyme deficiency affects glycolysis, leading to muscle cramps and weakness.
CHOICE G: Deficiency in glucose-6-phosphatase
Explanation: This enzyme deficiency causes Von Gierke's disease (Glycogen Storage Disease Type I), characterized by hypoglycemia, lactic acidosis, hepatomegaly, and elevated liver enzymes.
FINAL VERDICT…
The infant's symptoms of poor weight gain, recurrent hypoglycemia after fasting, lethargy, hepatomegaly, elevated liver enzymes, and lactate levels, along with a reducing substance in the urine, are indicative of Von Gierke's disease. This condition results from a deficiency in glucose-6-phosphatase, which impairs gluconeogenesis and glycogenolysis, leading to the accumulation of glycogen in the liver and kidneys.
CORRECT ANSWER: G) Deficiency in glucose-6-phosphatase
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