A laboratory puzzle in a "blue" adolescent: Cyanosis, discordant oxygen measurements, and interference in leukocyte differential analysis.

Methemoglobinemia caused by hemoglobin M variants is a rare inherited hemoglobinopathy characterized by lifelong cyanosis and discordant oxygen measurements. We report an 18-year-old male presenting with marked cyanosis, chocolate-brown blood, markedly reduced arterial oxygen saturation, normal arterial partial pressure of oxygen, and elevated methemoglobin levels. Complete blood count analysis on a Sysmex XN hematology analyzer revealed a global downward shift of fluorescence signals on the leukocyte differential scattergram with apparent pseudoeosinophilia, whereas parallel analysis on an ADVIA 2120 analyzer showed a normal leukocyte differential. Peripheral blood smear examination demonstrated no morphologic abnormalities. Hemoglobin electrophoresis and whole-genome sequencing identified a heterozygous HBB:c.190C > T (p.His64Tyr) mutation, confirming the diagnosis of Hb M Saskatoon-associated methemoglobinemia. This case highlights methemoglobin as an important but underrecognized source of analytical interference in fluorescence-based leukocyte differential analysis and underscores the need for integrated interpretation of scattergram features, cross-platform verification, and clinical context in automated hematology testing.