A patient with progressive external ophthalmoplegia, ptosis, and mitochondrial myopathy is found to have a deletion in mitochondrial DNA (mtDNA) affecting Complex I subunits. This patient's cells show markedly reduced Complex I (NADH: ubiquinone oxidoreductase) activity. The clinical feature that distinguishes Complex I deficiency from Complex IV deficiency in children is:

• A Complex I deficiency exclusively presents with Leigh syndrome
• B Complex IV deficiency does not cause lactic acidosis unlike Complex I deficiency
• C Complex I deficiency only affects cardiac muscle, not skeletal muscle
• D Complex I deficiency causes elevated lactate/pyruvate ratio >20; lactic acidosis from NADH accumulation ✓

Explanation

Complex I (NADH dehydrogenase) transfers electrons from NADH to ubiquinone. Deficiency impairs re-oxidation of NADH, causing cytoplasmic NADH accumulation which shifts the LDH equilibrium toward lactate formation — elevated lactate with elevated lactate-to-pyruvate ratio (>20 suggests ETC defect, vs. pyruvate dehydrogenase defect where ratio is typically normal). Complex IV (cytochrome c oxidase) deficiency also causes lactic acidosis and Leigh syndrome but typically has a lower lactate/pyruvate ratio. Both can cause Leigh syndrome. The L/P ratio differentiates ETC (NADH-dependent, high L/P) from PDH deficiency (pyruvate accumulation, normal/high L/P but also elevated pyruvate).

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.