A Rare Case of Acquired Methemoglobinemia Associated with Alkaptonuria

Abstract

We herein present a rare case of acquired methemoglobinemia associated with alkaptonuria. Alkaptonuria is a congenital error of metabolism caused by the deficiency of homogentisic acid oxidase, which subsequently results in the accumulation of homogentisic acid (HGA) in body tissues. As renal dysfunction progresses, the level of HGA excretion in the urine decreases and the blood concentration of HGA increases. HGA oxidizes oxyhemoglobin to methemoglobin, which can induce multiple organ failure accompanied by tissue hypoxia, intravascular hemolysis and metabolic acidosis. The mortality of this disease is high when alkaptonuria is associated with the presence of methemoglobinemia; therefore, treatment should be carefully planned in such cases.

Ochronosis Presenting as Methemoglobinemia

“…Although most complications of alkaptonuria are chronic in nature, there are reports of acute decompensation and death in patients with alkaptonuria and impaired renal function. More specifically, the development of methemoglobinemia in patients with alkaptonuria has been reported in the English literature in multiple adult patients . In all cases, methemoglobinemia followed a decline in renal function, leading to rapid accumulation of HGA in the serum.…”

“…In patients with alkaptonuria who develop renal disease, decreased urinary elimination of HGA can lead to rapid accumulation of HGA in the blood and tissues, causing diffuse skin pigmentation. Moreover, rapid accumulation of HGA and its byproducts in the serum can overwhelm the anti‐oxidant capacity of the body, resulting in oxidation of oxyhemoglobin to methemoglobin, inducing refractory methemoglobinemia .…”

Fatal oxidative haemolysis and methaemoglobinaemia in a patient with alkaptonuria and acute kidney injury

“…Rapidly fatal non-cardiac complications of AKU are not well recognized. One previously published case describes fatal haemolysis complicating acute kidney injury in AKU [ 2 ]; the addition of methaemoglobinaemia makes this case even more unusual, joining a handful of reports including a recently published case from Japan [ 4 ]. The cascade of events despite recovery of excretory renal function is a novel aspect of the case.…”

“…Specific treatment for methaemoglobinaemia including exchange transfusion is recommended when the affected fraction of Hb reaches 20%; however, this guidance is difficult to interpret in the context of a falling Hb with ongoing haemolysis where a lower percentage of methaemoglobinaemia is likely to have a more profound effect. Methylene blue has been used without obvious benefit [ 4 ]; its pro-oxidant capacity may exacerbate haemolysis in this setting and nephrotoxicity is an additional concern. Nitisonone is a reversible inhibitor of 4-hydroxyphenylpyruvate dioxygenase and rapidly reduces serum HGA [ 11 , 13 , 14 ].…”