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Journal of Inherited Metabolic Disease

, Volume 39, Issue 2, pp 203–210 | Cite as

Acute fatal metabolic complications in alkaptonuria

  • A. S. Davison
  • A. M. Milan
  • J. A. Gallagher
  • L. R. Ranganath
Review

Abstract

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.

Keywords

Chronic Kidney Disease Methylene Blue Acute Kidney Injury G6PD Deficiency Homogentisic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AKU

Alkaptonuria

HGA

Homogentisic acid

HGD

Homogentisate-1,2-dioxygenase

BQA

1,4-benzoquinone-2-acetic acid

AKI

Acute kidney injury

CKD

Chronic kidney disease

NAC

N-acetyl cysteine

RBCs

Red blood cells

MetHb

Methaemoglobin

PPP

Pentose phosphate pathway

NADH

Nicotinamide adenine dinucleotide

NADPH

Nicotinamide adenine dinucleotide phosphate

ROS

Reactive oxygen species

G6PD

Glucose-6-phosphate dehydrogenase

Notes

Compliance with ethical standards

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

Informed consent was obtained from patient(s) wherever included in this review.

Ethical Approval

This article does not contain any studies with human or animal subjects performed by the any of the authors.

Conflict of interest

None.

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Copyright information

© SSIEM 2015

Authors and Affiliations

  • A. S. Davison
    • 1
    • 2
  • A. M. Milan
    • 1
    • 2
  • J. A. Gallagher
    • 2
  • L. R. Ranganath
    • 1
    • 2
  1. 1.Department of Clinical Biochemistry and Metabolic Medicine, Liverpool Clinical LaboratoriesRoyal Liverpool University Hospitals TrustLiverpoolUK
  2. 2.Bone and Joint Research Group, Musculoskeletal BiologyUniversity of LiverpoolLiverpoolUK

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