Free Step 1-style question
Infant with doll-like facies, massive hepatomegaly, and fasting hypoglycemia with lactic acidosis.
An 8-month-old boy is brought to the pediatrician for evaluation of several episodes of tremors, sweating, and irritability that occur when he goes for more than 4 hours without feeding. Physical examination reveals a protuberant abdomen with a palpable liver edge 5 cm below the costal margin and a doll-like facial appearance with rounded, fat-filled cheeks. Laboratory studies are obtained and the results are shown below.
| Test | Value | Reference range |
|---|---|---|
| Serum glucose | 38 mg/dL | 70–110 mg/dL |
| Serum lactate | 6.4 mmol/L | 0.5–2.2 mmol/L |
| Serum uric acid | 12.1 mg/dL | 2.0–7.0 mg/dL |
| Serum triglycerides | 510 mg/dL | 35–135 mg/dL |
Which of the following is the most likely diagnosis?
- A. Andersen disease
- B. Cori disease
- C. McArdle disease
- D. Pompe disease
- E. Von Gierke disease
Correct answer: E. Von Gierke disease
This infant's fasting-triggered tremors and sweating, massive hepatomegaly with doll-like facies, hypoglycemia, lactic acidosis, hyperuricemia, and hypertriglyceridemia are consistent with Von Gierke disease, also called Type I glycogen storage disease, which is caused by a deficiency of glucose-6-phosphatase. This enzyme catalyzes the final step of both glycogenolysis and gluconeogenesis: the conversion of glucose-6-phosphate to free glucose. Its deficiency causes severe fasting hypoglycemia that does not respond to glucagon administration. Accumulation of glucose-6-phosphate shunts metabolic intermediates into alternative pathways: increased glycolysis results in lactic acidosis, increased pentose phosphate pathway activity leads to hyperuricemia due to increased ribose-5-phosphate and purine synthesis, compounded by decreased renal uric acid excretion as lactate competes for proximal tubular organic acid transport, and increased fatty acid synthesis leads to hypertriglyceridemia and hepatic steatosis. Physical examination typically reveals massive hepatomegaly and doll-like facies with rounded cheeks due to adipose tissue deposition.
Takeaway
Von Gierke disease (Type I GSD) is caused by glucose-6-phosphatase deficiency, resulting in severe fasting hypoglycemia, hepatomegaly, lactic acidosis, hyperuricemia, and hypertriglyceridemia.
What this page covers
Practice Step 1-style biochemistry questions on Von Gierke disease, with emphasis on clinical diagnosis vignette and answer-choice reasoning.
Step 1 practice focus
This preview is organized around Von Gierke disease in Glycogen Storage Diseases within Carbohydrate Metabolism. It is intended for students practicing clinical diagnosis vignette questions, where the goal is to connect the vignette clue pattern to the underlying biochemical pathway, enzyme defect, metabolite change, regulatory step, or physiologic consequence.
How to use this page
Review the topic and reasoning focus, then practice Step 1-style questions inside BiochemStep. The question set emphasizes mechanism-first answer-choice reasoning rather than passive content review.