= ALKAPTONURIA

[ochros, Greek = pale, light yellow brown color]

[alkapton from al-qaly, Arabic = potash + kapto, Greek = to suck up]

= rare inborn error of metabolism

Pathophysiology:

inherited absence of enzyme homogentisate 1,2-deoxygenase → inability to normally degrade aromatic amino acids tyrosine + phenylalanine → accumulation of their alternate degradation product homogentisic acid within bloodstream → excretion in urine + deposition in connective tissue (including cartilage, synovium, and bone)

Prevalence: 1÷250,00 to 1÷1,000,000 births; M÷F = 2÷1

Histo: black-pigmented cartilage subject to deterioration → calcification + denudation of cartilaginous tissue

• ochronosis =dark pigment in soft tissues (in 2^nd decade): yellowish skin; gray pigmentation of sclera; bluish tinge of auricular + nasal cartilage
• alkaptonuria with black staining of diapers (homogentisic acid in urine is oxidized to benzoquinones which form melanin-like polymers responsible for discoloration)
• heart failure, renal failure (pigment deposition)
• Spine
  Age: 3^rd–4^th decade
  Site: lumbar region with progressive ascension (cervical spine typically spared)
  • progressive kyphosis with loss of height
  • decreased lumbar flexion
  • CHARACTERISTIC laminated calcifications of multiple intervertebral disks (primarily of annulus fibrosus)
  • severe narrowing of intervertebral disk space + eventual obliteration
  • multiple “vacuum” phenomena (common)
  • osteopenia of adjoining vertebrae
  • loss of normal lumbar lordosis
  • massive vertebral osteophytosis (resembling syndesmophytes of ankylosing spondylitis) + ankylosis of spine (in older patient)
  • spotty calcifications in tissue anterior to vertebral bodies
• Joints = ochronotic arthropathy
  = manifestation of long-standing alkaptonuria in axial + peripheral skeleton similar to osteoarthritis
  • long-standing joint pain + limited range of motion
  • hypertrophic changes in humeral head
  • severe progressive premature osteoarthritis (knee >shoulder >hip):
    • joint narrowing + subchondral sclerosis
    • prominence of intraarticular osteochondral fragments
    • relative lack of prominent osteophyte formation
  • small calcifications in paraarticular soft tissues + tendon insertions

DDx: ankylosing spondylitis (erosions and ankylosis of SI joints, severe facet joint involvement)