alkaptonuria

Ochronosis, or alkaptonuria (AKU), is a rare multisystem autosomal recessive metabolic disorder.

On imaging, the most particular presentation is on the spine, with osteoporotic bones and dense disc calcifications.

Terminology

The term ochronosis usually refers to the bluish-black discolouration of certain tissues, such as the ear cartilage and the ocular tissue, seen with alkaptonuria. Some authorities, however, refer to musculoskeletal manifestations of alkaptonuria as ochronosis .

Epidemiology

The estimated incidence is around 1:250,000-1,000,000 .

Clinical presentation

Patients often have pigmentation of auricular cartilages and sclera. Urine color tends to be dark (at birth sometimes diagnosed by discolouration of diapers). Up to 25% of patients with alkaptonuria do not have the characteristic dark urine staining; many patients remain undiagnosed until adulthood.

Pathology

The condition results due to excessive build-up of homogentisic acid (HGA) from a lack of homogentisic oxidase (a defect in the biochemical pathway for the degradation of phenylalanine and tyrosine). The excess HGA binds to collagen in connective tissue. The affected connective tissues become weak and brittle with time, leading to chronic inflammation, degeneration, and osteoarthrosis (progressive arthropathy).

Genetics

 A defective gene has been mapped to chromosome 3q21–q23 .

Radiographic features

Plain radiograph

The most well-described features are those involving the skeletal system.

Vertebral
  • severe osteoporosis
  • multilevel intervertebral disc calcification: tends to be widespread (and involves nucleus pulposus)
  • syndesmophyte formation
  • multilevel disc space narrowing
Joints

Treatment and prognosis

There is currently (as of February 2018) no effective treatment for ochronosis.

Complications

History and etymology

Ochronosis was defined by Virchow, who histologically described the connective tissue in alkaptonuria, given the cartilage's ocher (yellow) hue under the microscope.

Differential diagnosis

For skeletal radiographic manifestations consider:

There is a broad differential for intervertebral disc calcification.

See also