Alkaptonuria (Ochronosis)

Definition

  • Rare hereditary disorder
  • Deficiency of Homogentisic Acid Oxidase » accumulation of Homogentisic Acid
  • Memory aid “ONC = HOG”

Characterised by

  • Homogentisic acid in urine
  • Dark pigmentation of connective tissues – Ochronosis
  • Calcification of hyaline & fibrocartilage – Chondrocalcinosis

Epidemiology

  • Autosomal recessive disorder
  • Usually presents with symptoms in 4th decade

Pathogenesis

  • Deletion of Homogentisic Acid Oxidase in the pathway concerned with metabolism of the amino acids Phenylalanine & Tyrosine
    • Accumulation of Homogentisic Acid occurs
    • Excreted in urine
    • Oxidisation (when urine left standing) & Alkalinisation (hence name “alkaptonuria”) of Homogentisic Acid turns urine black
  • Homogentisic Acid retained in body is deposited in
    • Articular & fibrocartilage
    • Skin
    • Sclerae
  • Pigment causes the collagen fibres to lose normal resilience
  • Becomes brittle & fibrillated
  • Degenerative changes in joints follow
  • May have pyrophosphate crystals in joint
  • Loose body formation not uncommon

Clinical Features

  • The first complaint is back pain & stiffness with deposition of pigment in the intervertebral discs & later calcification
  • May resemble Ankylosing Spondylitis but sacroiliac joints spared
  • Then large joint disease follows with classic degenerative changes & loose bodies frequent
  • Chondrocalcinosis common
  • Deposition of pigment in sclerae, pinna of ear & dark sweat (staining clothes) is commonly seen

Radiographically

  • See calcification & narrowing of intervertebral discs & surrounding osteoporosis
  • Severe osteoarthritis in peripheral joints with chondrocalcinosis

Treatment

  • No treatment for the metabolic disorder but may need surgery for arthritic joints