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Recent advances in understanding the pathogenesis of ochronosis: Najnowsze postępy w zrozumieniu patogenezy ochronozy

Research output: Contribution to Journal/MagazineJournal articlepeer-review

  • James Gallagher
  • Adam Taylor
  • Alan Boyde
  • Jonathan Jarvis
  • Lakshminarayan Ranganath
<mark>Journal publication date</mark>2012
Issue number4
Number of pages8
Pages (from-to)316–323
Publication StatusPublished
Early online date7/09/12
<mark>Original language</mark>English


Alkaptonuria (AKU) is an iconic disease caused by deficiency of the enzyme homogentisate 1,2-dioxygenase (HGD). Deficiency results in an increase in the circulating concentration of homogentisic acid (HGA), which over time is deposited as pigmented polymers in tissues including sclera, heart valves and cartilage, a process described as ochronosis. Joint ochronosis causes severe, early onset osteoarthritis. Studies on ex vivo tissue samples, in vitro cell cultures and mouse models of AKU indicate that tissues are initially resistant to ochronosis and become susceptible possibly following mechanical or oxidative damage and/or local metabolic changes. There is a lack of effective biomarkers to monitor the
progression of ochronosis and response to potential therapies but a disease severity index for AKU has recently been developed. Current studies are evaluating the efficacy of the potential therapy nitisinone in AKU. Research on ochronosis has led to the identification of several previously unrecognised pathophysiological features of the osteoarthritis phenotype.