Fact-sheet: Ochronosis


Updated on 07/10/2024 at 9:45 AM

Note : 10/10 ( 2 notes )
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Definition

Rare autosomal genetic disease affecting phenylalanine and tyrosine metabolism, characterized by accumulation of homogentisic acid (HGA) and its oxidation product, benzoquinone acetic acid (BQA). HGA is excreted in the urine.

The course and severity of clinical manifestations depend on the degree of enzyme deficiency.

Clinical features

Often asymptomatic until adulthood.

  • Ochronotic pigmentation of the sclera, then of the skin: ears (conchae, antihelix, tragus), nasal alae, axillae, thenar and hypothenar eminences, genital areas.
  • Ochronotic arthropathy (starting at age 30-40): spinal pain and progressive stiffness, lumbar then thoracic then cervical. Postural abnormalities (kyphosis, scoliosis). Involvement of the large peripheral joints generally occurs several years after that of the spine. Decreased joint mobility, ankylosis, fractures. Tendon and ligament ruptures may occur.
  • Genitourinary complications: renal, bladder, and prostatic calculi.
  • Cardiac complications: mitral valvulitis, arrhythmias
  • Respiratory failure due to musculoskeletal involvement.
  • Secondary AA amyloidosis is frequently associated (on histological and biochemical grounds).

Laboratory findings

  • Urinary homogentisic acid: markedly increased (1 to 20 g/day versus 0 normally).
  • Generally, no biological inflammatory syndrome.

Radiography

Radiographic findings of ochronotic arthropathy

  • Spine: Multilevel disc calcifications visible early in the course, disappearing with ankylosis.
  • Composition: apatite crystals of dystrophic origin.
  • They initially involve the center of the disc, then the entire disc.
  • Severe multilevel discopathy with marked narrowing of the intervertebral discs and multilevel intradiscal vacuum phenomenon.
  • Osteosclerosis and mild marginal osteophytosis of the adjacent vertebral endplates.
  • Progressive ossification: bony bridges and intersomatic ankylosis, sometimes mimicking ankylosing spondylitis
  • Postural abnormalities: loss of lumbar lordosis
  • thoracic hyperkyphosis
  • scoliosis
  • Appendicular skeleton: Bilateral and symmetric extraspinal arthropathies: knees (70%), shoulders (40%), and hips (30%)
  • Severe degenerative changes: often global joint space narrowing, moderate osteophytosis, subchondral osteosclerosis, bone fragmentation.
  • Possible tendinous and bursal calcifications.
  • Diffuse osteopenia

CT

Semiotics identical to radiographs

MRI

Signal abnormalities of the vertebral endplates adjacent to the discs on MRI:

signal predominantly fatty in type (Modic type II) or sclerotic in type (Modic type III)

Management

No etiologic treatment.

Dietary management: diets low in phenylalanine and tyrosine, combined with daily intake of ascorbic acid

Analgesics and nonsteroidal anti-inflammatory drugs

Nitisinone (promising results but long-term efficacy and safety require further studies)

Physiotherapy and physical therapy

Surgery: Spinal stabilization. Hip or knee arthroplasty.

Differential diagnosis

Acute intermittent porphyria

Rheumatoid arthritis

Ankylosing spondylitis

Osteoarthritis