Leigh syndrome (subacute necrotising encephalomyelopathy) in infants is most commonly due to mutations in mitochondrial ATP synthase subunit 6 or Complex I subunits. Which metabolic parameter is MOST elevated in a patient with Leigh syndrome during metabolic crisis?
- A Lactate:pyruvate ratio (L:P ratio) ✓
- B Plasma glucose
- C Ammonia
- D Uric acid
Correct answer: A. Lactate:pyruvate ratio (L:P ratio)
Explanation
In mitochondrial respiratory chain disorders (Complex I, IV, V, or ATP synthase defects), oxidative phosphorylation is impaired, shifting the NAD+:NADH ratio. Excess NADH drives the lactate dehydrogenase (LDH) reaction toward lactate, while pyruvate levels may be normal or low. The lactate:pyruvate (L:P) ratio normally is 10:1; in mitochondrial disorders it rises >20:1 (often >30:1), distinguishing mtOXPHOS defects from pyruvate dehydrogenase deficiency (where both lactate and pyruvate rise with a normal L:P ratio). The L:P ratio is a key discriminating biomarker.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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