Fatal methemoglobinemia complicating alkaptonuria (ochronosis): a rare presentation

Amanda R. Freeman, Stephen M. Wills

A 61-year-old female died in hospital with multiple organ failure 4 weeks following presentation with acute kidney injury, hemolytic anemia and methemoglobinemia. At autopsy, brown to black discoloration of cartilages was observed. Histology revealed brown pigmentation of the hyaline cartilage, with focal full-thickness erosion of the articular hyaline cartilage, characteristic of alkaptonuria (ochronosis). Although alkaptonuria is rarely fatal, this case illustrates a rare acute fatal complication. Accumulation of circulating homgentisic acid secondary to acute derangement of renal function is believed to have overwhelmed the endogenous antioxidant processes, resulting in hemolysis and methemoglobinemia, which were refractory to treatment. Small numbers of cases have previously been reported in the literature in patients known to suffer with the disease, all of which were preceded by acute kidney injury. Whilst the clinical diagnosis of alkaptonuria may be challenging, the autopsy findings of this rare condition are striking and this case illustrates the utility of the autopsy, albeit retrospectively, in arriving at a diagnosis. To our knowledge this is the first reported case where previously undiagnosed alkaptonuria has presented with methemoglobinemia.