Clinical Scenario:
A 9-month-old boy is brought with recurrent episodes of vomiting, lethargy, and seizures, particularly during periods of fasting or intercurrent illness. His parents report that he becomes symptomatic after prolonged overnight fasting but improves rapidly after receiving intravenous glucose. On examination, he is lethargic with mild hepatomegaly. Laboratory investigations during an episode reveal:
Blood glucose: 32 mg/dL
Serum ketones: Absent
Serum ammonia: Normal
Arterial blood gas: Normal
What is the most likely diagnosis?
A. Galactosemia
B. Glycogen storage disease type I
C. Medium-chain acyl-CoA dehydrogenase deficiency
D. Maple syrup urine disease
E. Urea cycle defect
Correct answer & Explanation:
Correct Answer C. Medium-chain acyl-CoA dehydrogenase deficiency
Discussion
This child has:
Recurrent episodes precipitated by fasting
Severe hypoglycemia
Absent ketones (hypoketotic hypoglycemia)
Improvement with glucose administration
Mild hepatomegaly
The inability to generate ketone bodies during fasting is the key clue. Normally, fatty acid oxidation provides energy and ketones during fasting. In MCAD deficiency, fatty acid oxidation is impaired, leading to:
Hypoglycemia
Low or absent ketones
Lethargy, seizures, coma
Risk of sudden death during fasting illnesses
Why the Other Options Are Incorrect
A. Galactosemia
Presents after milk feeding with jaundice, hepatomegaly, and cataracts.
Hypoketotic hypoglycemia is not typical.
B. Glycogen Storage Disease Type I
Causes fasting hypoglycemia but is usually associated with ketosis, hyperlactatemia, and marked hepatomegaly.
D. Maple Syrup Urine Disease
Presents with poor feeding, encephalopathy, and ketosis.
Characteristic sweet odor of urine.
E. Urea Cycle Defect
Presents with hyperammonemic encephalopathy.
Blood glucose is usually normal.
Postgraduate Pearl
Hypoketotic hypoglycemia in a child with recurrent fasting intolerance is a classic clue to a fatty acid oxidation disorder, particularly Medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency). The inability to produce ketones despite profound hypoglycemia is the diagnostic hallmark.
