HGD deficiency leads to the accumulation of homogentisic acid (HGA) that can be excreted in the urine (homogentisic aciduria) or can oxidize and polymerize to form an ochronotic
pigment that is deposited in the connective tissues (ochronosis) or within the joints (ochronotic
The deficiency of homogentisate 1,2 dioxygenate (HGD) leads to an accumulation of homogentisic acid (HGA) in plasma and urine which auto-oxidizes in tissues into benzoquinone acetic acid and polymerizes to an ochronotic
There was no ochronotic
findings in the other members of the family.
However, pathological tissue pigmentation is occasionally induced under several specific conditions, including ochronotic
arthritis accompanied by alkaptonuria [1-3], haemosiderosis , and the use of drugs for Parkinson's disease [5, 6] or antibiotics [7-9].
AKU is caused by the deficiency of the homogentisate 1,2-dioxygenase enzyme which results in excretion of large quantities of homogentisic acid (HGA) in the urine and a slowly progressive deposition of HGA and its oxidative product in cartilage, intervertebral disk and other connective tissues, leading to ochronotic
Antiresorptive drugs such as alendronate and ibandronic acid are not proven to benefit in ochronotic
spine with osteopenia.
The differential diagnosis includes iron and ochronotic
Rare conditions such as hemochromatosic arthropathy , ochronotic
arthropathy , Wilson's disease , and oxalate crystal deposition disease  can lead to difficult clinical situations.
By means of our in vitro cell and tissue AKU models we also proved that HGA is responsible for pigment and SAA and amyloid production and a colocalization of ochronotic
pigment and SAA-amyloid was also reported [9, 11-19].
The management of ochronotic
arthropathy is usually conservative, but replacement surgery must be offered for severely affected major joints.
The major clinical manifestations of the disease are dark urine, usually present at birth, ochronosis (blue-dark pigmentation of connective tissues), and ochronotic
arthropathy, which especially affects the large weight-bearing joints and spine and typically appears after the age of thirty.
Aortotomy revealed typical ochronotic
pigmentation of a severely calcified aortic valve and aortic intima.