From the Research
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency most likely leads to underproduction of acetyl-CoA, as it is a crucial enzyme in the beta-oxidation pathway of medium-chain fatty acids. MCAD is responsible for breaking down fatty acids with 6-12 carbon atoms, and its deficiency results in decreased production of acetyl-CoA, the end product of fatty acid oxidation 1. This reduction in acetyl-CoA production has significant metabolic consequences, as acetyl-CoA is a crucial intermediate that enters the Krebs cycle for energy production.
The pathogenesis of MCAD deficiency involves the accumulation of medium-chain acylcarnitines and medium-chain dicarboxylic acids in the blood and urine, leading to hypoketotic hypoglycemia, lethargy, and metabolic acidosis during periods of fasting or illness 1. Patients with MCAD deficiency typically present with these symptoms when the body would normally rely on fatty acid oxidation for energy.
Key aspects of MCAD deficiency management include:
- Avoiding prolonged fasting
- Maintaining adequate carbohydrate intake
- Sometimes supplementing with L-carnitine to help remove accumulated metabolites Given the rapid developments in gene therapy and newborn screening, it is essential for clinicians to have up-to-date knowledge on the pathogenesis, diagnosis, and treatment options for MCAD deficiency patients 1.