Case Presentation: A 43 year old Albanian man without any significant past medical history, presented to the hospital with sudden onset intermittent dyspnea, chills and dark urine of 4 days duration. He had started consuming fava beans for the first time in his life, 2 weeks prior to presentation. Examination revealed scleral icterus, conjunctival pallor and sublingual cyanosis. His arterial oxygen saturation (SaO2) was 86% on pulse-oximetry but 100% on arterial blood gas (ABG). This prompted checking a methemoglobin (MetHb) level which was elevated at 8%. He did not have hepatomegaly or splenomegaly. Laboratory workup revealed hemoglobin of 8 g/dL (14 g/dL at baseline), leukocytosis, hyperbilirubinemia, hemoglobinuria, elevated LDH, high reticulocyte index and low haptoglobin. Peripheral smear demonstrated polychromasia, nucleated RBCs, anisocytosis and spherocytes. EKG, chest x-ray and troponin were unremarkable. Management was initiated with oxygen, RBC transfusion, intravenous fluids and low dose ascorbic acid. During his hospital course of 3 days, leukocytosis resolved and anemia responded adequately to transfusion. His symptoms, cyanosis and jaundice also resolved and oxygen saturation normalized to 100% on pulse-oximetry. He was prescribed folic acid on discharge, and provided with a list of medications and foods including Fava beans to avoid. On follow up, he remained asymptomatic, anemia resolved and G6PD level was 1.5 unit/g of Hemoglobin (normal 8-13).
Discussion: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder which makes red blood cells (RBCs) more susceptible to oxidant stress. It is the most common enzyme deficiency of the RBCs, affecting approximately 400 million people around the world. The ingestion of Fava beans in these individuals usually triggers acute hemolysis, but is rarely severe enough to cause Methemoglobinemia. Studies report certain medications and infections triggering isolated hemolysis in G6PD deficient adults. A thorough PubMed search yielded only 4 reports of G6PD deficient adults developing both hemolysis and Methemoglobinemia and none of these cases implicated Fava beans as the inciting factor. Our patient demonstrated clinical and laboratory features of hemolytic anemia. The cyanosis, discrepancy between SaO2 on pulse-oximetry and ABG with a normal paO2 pointed towards Methemoglobinemia, which was confirmed by elevated MetHb. His Mediterranean descent raised concern for G6PD deficiency. Methylene blue is considered if the patient is symptomatic or if MetHb is greater than 20%, however it is ineffective and may worsen the hemolysis in G6PD deficiency. Low enzyme level obtained after resolution of acute hemolysis established the diagnosis of G6PD deficiency. The ingestion of Fava beans shortly prior to symptom onset, and resolution of illness on avoidance, implicates it as the oxidant stress.
Conclusions: Hemolysis in an adult of Mediterranean descent should raise concern for G6PD deficiency. Heinz bodies and Bite cells are characteristic of these cases but their absence does not exclude the diagnosis. Methylene blue should not be used to manage Methemoglobinemia in diagnosed or suspected G6PD deficiency. Ascorbic acid should be used as antioxidant as it does not require G6PD to reduce MetHb. This case demonstrates the “textbook” presentation of Favism causing hemolytic anemia along with Methemoglobinemia in a G6PD deficient adult, which is unique to the current body of literature.