Clinical Scenario:
A 9-month-old boy is brought with recurrent episodes of fasting hypoglycemia, progressive hepatomegaly, and poor weight gain. Examination reveals a protuberant abdomen with enlarged liver but normal muscle strength. Laboratory investigations show severe hypoglycemia, hyperuricemia, hypertriglyceridemia, and elevated lactate levels. Which glycogen storage disease is the most likely diagnosis?
A. Glycogen storage disease type I (Von Gierke disease)
B. Glycogen storage disease type II (Pompe disease)
C. Glycogen storage disease type III (Cori disease)
D. Glycogen storage disease type V (McArdle disease)
E. Glycogen storage disease type VI (Hers disease)
Correct answer & Explanation:
Correct Answer:
A. Glycogen storage disease type I (Von Gierke disease)
Explanation:
Glycogen storage disease type I (Von Gierke disease) results from deficiency of glucose-6-phosphatase (type Ia) or the glucose-6-phosphate transporter (type Ib). Because glucose cannot be released from the liver during fasting, affected infants develop:
- Severe fasting hypoglycemia
- Hepatomegaly due to glycogen accumulation
- Lactic acidosis
- Hyperuricemia
- Hypertriglyceridemia
- Failure to thrive and a protuberant abdomen
These biochemical abnormalities are highly characteristic of GSD I.
Why the other options are incorrect:
- B. Pompe disease (GSD II): Causes hypertrophic cardiomyopathy, hypotonia, and macroglossia. Hypoglycemia is not a prominent feature.
- C. Cori disease (GSD III): Produces hepatomegaly and hypoglycemia, but lactic acidosis and marked hyperuricemia are usually absent. Creatine kinase is often elevated because of muscle involvement.
- D. McArdle disease (GSD V): Presents later in childhood or adulthood with exercise intolerance, muscle cramps, and myoglobinuria; liver is not involved.
- E. Hers disease (GSD VI): Causes mild hepatomegaly and mild fasting hypoglycemia without the severe metabolic derangements seen in GSD I.
Key learning point:
The combination of severe fasting hypoglycemia + hepatomegaly + lactic acidosis + hyperuricemia + hypertriglyceridemia is the classic biochemical signature of Glycogen Storage Disease Type I (Von Gierke disease). This characteristic biochemical pattern strongly suggests GSD I and helps distinguish it from other hepatic glycogen storage diseases.
You can practice another MCQ on Glycogen Storage Disease.
References
- 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. Updated October 14, 2021.
- Kishnani PS, Austin SL, Abdenur JE, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med. 2014;16(11):e1.
- Kliegman RM, St Geme JW III, Blum NJ, Shah SS, Tasker RC, Wilson KM, editors. Nelson Textbook of Pediatrics. 22nd ed. Philadelphia: Elsevier; 2024.
