Ochronosis aka Alkaptonuria - Important facts

Ochronosis

1. Ochronosis/Alkaptonuria
Inborn error of  tyrosine metabolism
Autosomal recessive mutation of  HGD (Homogentisic acid), 
at least 203 variants
1:250,000 to 1:1,000,000, higher in Dominican Republic 
and Slovakia
Pathogenesis: yellow
Presentation: blue
Labs/Image: red
Histopathology: magenta
Treatment : green
Extra: gray
Typical triad (urine, cutaneous, arthritis)
High levels of HGA and its oxidized 
byproducts can affect collagen 
crosslinking, leading to increased cartilage 
stiffness and structural weakness
First early sign
Dark urine upon oxidation or alkalization
21% were diagnosed before 1 yo
Ochronotic arthropathy
(later signs)
3rd decade of life
Peripheral: knee (64%) > shoulders (43%) 
> hip/pelvis (35%); tendon, 
enthesopathy, in 50-60s
Axial: lumbar, thoracic > cervical (spares SI), mimic AS, 
usually in 30-40s
Typical radiographic findings (broad syndesmophytes, dense 
wafer-​ like disc calcification, vacuum phenomenom
Aortic  or mitral  valve 
calcification was detected 
at a mean age of 54
24-​hour urinary excretion of HGA
plasma homogentisate level
DNA testing for genetic 
mutations of the HGD gene
25% has elevated ESR
ochronotic pigmentation, 
thickened synovium with 
synovitis, and reactive 
giant cells,  pigment 
containing macrophages
Nitisinone (Orfadin) => reduce 
plasma and urine HGA by 95%