TY - JOUR

T1 - Recent advances in understanding the pathogenesis of ochronosis

T2 - Najnowsze postępy w zrozumieniu patogenezy ochronozy

AU - Gallagher, James

AU - Taylor, Adam

AU - Boyde, Alan

AU - Jarvis, Jonathan

AU - Ranganath, Lakshminarayan

PY - 2012

Y1 - 2012

N2 - 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 theprogression 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.

AB - 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 theprogression 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.

KW - alkaptonuria

KW - ochronosis

KW - homogentisic acid

KW - osteoarthritis

M3 - Journal article

VL - 50

SP - 316

EP - 323

JO - Reumatologia

JF - Reumatologia

SN - 2084-9834

IS - 4

ER -