Biochemical deciphering of an Atypical Methemoglobinemia

Methemoglobin is formed when the iron in hemoglobin is oxidized from the ferrous to the ferric state, preventing oxygen transport. This potentially life-threatening condition requires prompt diagnosis and treatment. We report the case of a 30-year-old Senegalese man with newly diagnosed acute leukemia, admitted to the emergency department for suspected leukostasis syndrome. Induction chemotherapy and rasburicase were initiated. Unexpectedly, 24-hours later, he developed acute hemolysis and a methemoglobinemia of 17%. Investigation suggested rasburicase-induced methemoglobinemia. Rasburicase generates hydrogen peroxide during acid uric metabolism, normally neutralized by glutathione reductase, an enzyme that requires NADPH, which is produced via the pentose phosphate pathway. In this case, the presence of severe hemolytic anemia and marked susceptibility to oxidative stress prompted comprehensive laboratory investigations, including glucose-6-phosphate dehydrogenase deficiency testing, which returned positive. Supportive care, including monitoring, blood transfusions, and oxygen therapy, allowed normalization of methemoglobin levels within 48-hours. Methemoglobin can serve as a sentinel marker for the detection and monitoring of oxidative stress and related hematologic disorders. This case highlights the laboratory’s role in identifying such abnormalities and the importance of clinician-laboratory awareness regarding rasburicase-induced methemoglobinemia. It also suggests the necessity of G6PD screening prior to rasburicase administration whenever possible. Highlights : • Rasburicase generates H 2 O 2 normally neutralized by glutathione reductase and NADPH • Hemolytic anemia and methemoglobinemia can occur after rasburicase administration • Rasburicase-induced methemoglobinemia revealed G6PD deficiency • Suspected rasburicase-induced methemoglobinemia requires G6PD deficiency testing • If possible, test G6PD activity before rasburicase; if not, monitor methemoglobin