An 18-month-old with hypoglycemia, lethargy, diarrhea, and dicarboxylic acids improves with medium-chain triglyceride therapy after IV treatment. Which enzyme deficiency is most likely?

An 18-month-old with hypoglycemia, lethargy, diarrhea, and dicarboxylic acids improves with medium-chain triglyceride therapy after IV treatment. Which enzyme deficiency is most likely?

• A. Pyruvate dehydrogenase
• B. Long-chain acyl-CoA dehydrogenase
• C. Medium-chain acyl-CoA dehydrogenase
• D. Carnitine palmitoyltransferase deficiency

Answer: (B)

Fatty acid oxidation disorders that present with fasting hypoglycemia and dicarboxylic acids in urine point to a block in breaking down long-chain fatty acids. When beta-oxidation of long chains is impaired, the body gets energy mainly from glucose, and fat-derived energy is limited, especially during fasting. Dicarboxylic acids arise because the body tries to compensate by ω-oxidation of long-chain fatty acids, leading to those distinctive byproducts. The way the patient responds to medium-chain triglyceride therapy is key: medium-chain fatty acids can be absorbed and enter mitochondrial beta-oxidation without needing the long-chain specific dehydrogenase. They provide an energy source despite the block in long-chain fatty acid oxidation. This means the defect is specifically in the enzyme that handles long-chain substrates. Among the possible defects, the enzyme responsible for dehydrogenating long-chain acyl-CoAs is defective in this scenario, consistent with a long-chain acyl-CoA dehydrogenase deficiency.

Fatty acid oxidation disorders that present with fasting hypoglycemia and dicarboxylic acids in urine point to a block in breaking down long-chain fatty acids. When beta-oxidation of long chains is impaired, the body gets energy mainly from glucose, and fat-derived energy is limited, especially during fasting. Dicarboxylic acids arise because the body tries to compensate by ω-oxidation of long-chain fatty acids, leading to those distinctive byproducts.

The way the patient responds to medium-chain triglyceride therapy is key: medium-chain fatty acids can be absorbed and enter mitochondrial beta-oxidation without needing the long-chain specific dehydrogenase. They provide an energy source despite the block in long-chain fatty acid oxidation. This means the defect is specifically in the enzyme that handles long-chain substrates.

Among the possible defects, the enzyme responsible for dehydrogenating long-chain acyl-CoAs is defective in this scenario, consistent with a long-chain acyl-CoA dehydrogenase deficiency.