title: Fatal oxidative haemolysis and methaemoglobinaemia in a patient with alkaptonuria and acute kidney injury.
abstract: Alkaptonuria (AKU) is a rare inherited disorder of tyrosine metabolism, which leads to an accumulation of homogentisic acid (HGA) and is associated with a progressive arthropathy. Fatal complications are unusual and usually result from cardiac disease or progressive renal impairment; rapidly fatal haematological complications are exceptionally rare and described in only a handful of case reports. This case involves a 63-year-old male with AKU and modest chronic kidney disease who developed rapidly fatal haemolysis and methaemoglobinuria following an episode of acute kidney injury triggered by an obstructing ureteric calculus and urosepsis. The patient succumbed despite aggressive antioxidant therapy with ascorbic acid and n-acetyl cysteine. A rapid build-up of HGA due to reduced renal clearance, triggering oxidative haemolysis and methaemoglobinuria is proposed as the mechanism. Alternative strategies to consider when conventional antioxidants fail are discussed including the potent inhibitor of HGA production, nitisonone.
authors.affiliation: Renal Unit , Aberdeen Royal Infirmary , Aberdeen , UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Mullan
authors.affiliation: Royal Liverpool University Hospital , Liverpool , UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Cocker
authors.affiliation: Department of Haematology , Aberdeen Royal Infirmary , Aberdeen , UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: Taylor
authors.affiliation: Renal Unit , Aberdeen Royal Infirmary , Aberdeen , UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Millar
authors.affiliation: Department of Clinical Biochemistry and Metabolic Medicine , Royal Liverpool Hospital , Liverpool , UK.
authors.forename: Lakshminarayan
authors.initials: L
authors.lastname: Ranganath
keywords: acute kidney injury; alkaptonuria; homogentisic acid; methaemoglobinaemia; oxidative haemolysis