In a patient with congenital cyanosis from birth, pulse oximetry reads 85% SpO2 but arterial blood gas shows normal PaO2. Heinz body test is negative. Spectroscopy shows an absorption peak at 630 nm. The most likely diagnosis and the enzymatic defect causing this condition is:

• A Sulfhemoglobinemia; deficiency of sulfhemoglobin oxidase
• B Methemoglobinemia; deficiency of NADH-cytochrome b5 reductase (methemoglobin reductase) ✓
• C Carboxyhemoglobinemia; deficiency of hemeoxygenase-1
• D HbM disease; structural beta-chain mutation

Explanation

Methemoglobin (Fe3+) has an absorption peak at ~630 nm (chocolate-brown blood), and pulse oximetry reads ~85% regardless of true saturation. Normal PaO2 with low SpO2 is pathognomonic of dyshemoglobinaemia. Congenital methemoglobinemia is caused by deficiency of NADH-dependent cytochrome b5 reductase (diaphorase I), which normally reduces Fe3+-Hb back to Fe2+-Hb using NADH generated by glycolysis. Treatment is methylene blue (requires NADPH from G6PD/HMP shunt) or ascorbic acid. HbM variants also cause congenital methemoglobinemia but Heinz bodies are absent in both; the question indicates enzyme deficiency (inherited as autosomal recessive).

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

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Written and medically reviewed by the StethoPrep medical team.