Clinical Scenario:
A 20-month-old boy is brought to the emergency department with recurrent early-morning seizures. His parents report that he becomes lethargic if meals are delayed for more than 4 hours. Examination reveals short stature, a protuberant abdomen, and hepatomegaly. Laboratory investigations during fasting show:
- Blood glucose: 32 mg/dL
- Lactate: 8.5 mmol/L (elevated)
- Uric acid: 9.2 mg/dL (elevated)
- Triglycerides: 480 mg/dL (elevated)
- Plasma ketones: Present
Which of the following is the most likely diagnosis?
A. Fatty acid oxidation defect
B. Fructose-1,6-bisphosphatase deficiency
C. Glycogen storage disease type I
D. Glycogen storage disease type III
E. Medium-chain acyl-CoA deficiency
Correct answer & Explanation:
Correct Answer: C. Glycogen Storage Disease Type I
Explanation
Glycogen storage disease (GSD) type I (Von Gierke disease) is caused by glucose-6-phosphatase deficiency, preventing the final step of glycogenolysis and gluconeogenesis.
Classic biochemical features include:
- Severe fasting hypoglycemia
- Lactic acidosis
- Hyperuricemia
- Hypertriglyceridemia
- Hepatomegaly
- Growth failure
The combination of hypoglycemia + lactic acidosis + hyperuricemia + hyperlipidemia is highly characteristic of GSD I.
Why the other options are incorrect
- A. Fatty acid oxidation defect – Causes hypoketotic hypoglycemia without marked lactic acidosis or hepatomegaly.
- B. Fructose-1,6-bisphosphatase deficiency – Causes hypoglycemia and lactic acidosis but usually presents during fasting or infection without hyperuricemia and marked hypertriglyceridemia.
- D. Glycogen storage disease type III – Causes hepatomegaly and ketotic hypoglycemia, but lactate is typically normal.
- E. Medium-chain acyl-CoA deficiency – Causes hypoketotic hypoglycemia with low ketones rather than elevated ketones.
High-Yield Pearl
Severe fasting hypoglycemia + hepatomegaly + lactic acidosis + hyperuricemia + hypertriglyceridemia = Glycogen Storage Disease Type I (Von Gierke disease).
You can practice another MCQ on metabolic disorder presented with cardiomyopathy and syndromic features.
References
- Kishnani PS, Austin SL, Arn P, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics. Genet Med. 2014;16(11):e1.
- Bali DS, El-Gharbawy A, Austin S, Pendyal S, Kishnani PS. Glycogen Storage Disease Type I. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026.
