Acute fatal metabolic complications in alkaptonuria
Alkaptonuria (AKU) is a rare inherited metabolic disorder of tyrosine metabolism that results from a defect in an enzyme called homogentisate 1,2-dioxygenase. The result of this is that homogentisic acid (HGA) accumulates in the body. HGA is central to the pathophysiology of this disease and the consequences observed; these include spondyloarthropathy, rupture of ligaments/muscle/tendons, valvular heart disease including aortic stenosis and renal stones. While AKU is considered to be a chronic progressive disorder, it is clear from published case reports that fatal acute metabolic complications can also occur. These include oxidative haemolysis and methaemoglobinaemia. The exact mechanisms underlying the latter are not clear, but it is proposed that disordered metabolism within the red blood cell is responsible for favouring a pro-oxidant environment that leads to the life threatening complications observed. Herein the role of red blood cell in maintaining the redox state of the body is reviewed in the context of AKU. In addition previously reported therapeutic strategies are discussed, specifically with respect to why reported treatments had little therapeutic effect. The potential use of nitisinone for the management of patients suffering from the acute metabolic decompensation in AKU is proposed as an alternative strategy.
KeywordsChronic Kidney Disease Methylene Blue Acute Kidney Injury G6PD Deficiency Homogentisic Acid
Acute kidney injury
Chronic kidney disease
Red blood cells
Pentose phosphate pathway
Nicotinamide adenine dinucleotide
Nicotinamide adenine dinucleotide phosphate
Reactive oxygen species
Compliance with ethical standards
All procedures reported in this review were in accordance with the ethical standards of the local Hospital ethics committee and with the Helsinki Declaration of 1975, as revised in 2000.
Informed consent was obtained from patient(s) wherever included in this review.
This article does not contain any studies with human or animal subjects performed by the any of the authors.
Conflict of interest
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