Introduction: Alkaptonuria (AKU) is a rare disorder of the tyrosine metabolic pathway that results in significant accumulation of homogentisic acid (HGA). A fatal complication of AKU is the development of hemolysis and methemoglobinemia. The pathophysiology is thought to be secondary to HGA buildup alongside its oxidative metabolite benzoquinone acetic acid that causes the oxidization of hemoglobin to methemoglobin. This rare and fatal phenomenon has only been described six other times in literature. Description: The patient is a 66 y/o male with PMHx of HFpEF, COPD, AKU who initially presented with a CHF exacerbation. He developed an AKI during diuresis requiring HD. Seven days into his admission he developed hypoxia. An ABG was drawn that showed dark chocolate-colored blood with PO2 of 346. Methemoglobin level was too high to be calculated. LDH was 1,093, haptoglobin undetectably low, and potassium was 6.5, consistent with hemolysis. The patient was started on CVVH. Peripheral smear showed anisopoikilocytosis with bite and blister cells consistent with oxidative hemolysis. The patient was given methylene blue with improvement in his methemoglobin level to 45.4%. The patient was given N-acetylcysteine and high dose ascorbic acid for antioxidant affects. Both plasma exchange and RBC exchange transfusion were utilized to treat the hemolytic anemia. Methemoglobin levels normalized and the patient’s condition stabilized. The orphan drug Nitisinone was emergently obtained. The patient developed a severe ischemic hepatocellular injury 36 hours after presentation resulting in overwhelming vasoplegic shock. He was compassionately extubated and passed shortly after. Discussion: Previous patients have been treated with a combination of antioxidants, methylene blue, and transfusions. Our patient’s condition was rapidly identified and aggressively treated with methylene blue, CVVH, ascorbic acid, NAC, plasma exchange, and exchange transfusion with significant improvement in his condition. Nitisinone, an inhibitor of an upstream enzyme that reduces the production of HGA, was also obtained and started within 24 hours. This combination of therapies has not been reported in literature. We suspect that the combination of our treatments was successful, and it was the initial ischemic injury that led to his demise.
Brownell et al. (Sun,) studied this question.