Asian Hematology Research Journal

Congenital methaemoglobinaemia is a rare disorder that may be overlooked when persistent cyanosis and low pulse-oximetry readings are attributed to cardiopulmonary disease. We report a 20-year-old male who presented with fever, peripheral cyanosis, clubbing and mild dizziness during the COVID-19 pandemic. Persistent SpO₂ readings of 86–87% led initially to isolation and treatment for suspected COVID-19, despite two negative RT-PCR tests and normal chest radiography, echocardiography, chest CT and CT pulmonary angiography. Subsequent arterial blood gas analysis showed pO₂ of 113 mmHg, while co-oximetry demonstrated MetHb 35.2%, O₂Hb 60.7%, HHb 4.1% and sO₂ 93.7%, with calculated sO₂(c) 98.4%. Clinical exome sequencing identified a homozygous likely pathogenic CYB5R3 variant, NM_000398.7:c.148C>T (p.Arg50Trp), supporting congenital methaemoglobinaemia. Erythrocyte cytochrome-b5-reductase activity was not measured, so a definitive biochemical subtype could not be established. The combined clinical, co-oximetry and genetic findings supported the final diagnosis. The patient commenced vitamin C tablets in March 2022, and follow-up in April documented improvement in symptoms and cyanosis. This case highlights the diagnostic value of considering methaemoglobinaemia when cyanosis and pulse-oximetry findings remain unexplained by routine cardiopulmonary investigations, particularly when oxygen measurements are discordant.