In fatty acid beta-oxidation, the very first step after acyl-CoA entry into the mitochondria is catalyzed by acyl-CoA dehydrogenase. Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited fatty acid oxidation disorder. Which metabolite accumulates and is detected on newborn screening?
- A Propionyl-CoA
- B 3-Hydroxybutyrate
- C Octanoylcarnitine (C8-acylcarnitine) ✓
- D Long-chain hydroxyl acylcarnitines
Correct answer: C. Octanoylcarnitine (C8-acylcarnitine)
Explanation
MCADD impairs oxidation of 6-12 carbon chain fatty acids. Medium-chain acyl-CoA species (especially C8, octanoyl-CoA) accumulate and are transferred to carnitine, generating elevated octanoylcarnitine (C8-acylcarnitine) in blood, which is the primary marker on tandem mass spectrometry (MS/MS) newborn screening. Affected children present with hypoketotic hypoglycemia during fasting because they cannot generate ketone bodies from fatty acids. Propionyl-CoA accumulates in methylmalonic/propionic acidemia; long-chain hydroxy-acylcarnitines in LCHAD deficiency.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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