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 ³. The term ochronosis originates from ‘Ocher / ώχρα’ in Greek meaning a dark yellow color, but can progress to bluish grey and black.

Epidemiology

The estimated incidence is around 1:250,000-1,000,000 ^3,5.

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 amino acids 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 ⁵.

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)

• multilevel vacuum phenomenon

• syndesmophyte formation

• multilevel disc space narrowing

Joints

• symmetrical or asymmetrical joint space loss: early osteoarthritis

• subchondral sclerosis

• chondrocalcinosis

• most commonly in the knee joint; however, the shoulder, the hip and other joints can also be involved

Treatment and prognosis

As of April 2023, there is no effective treatment for alkaptonuria. A low-protein diet is recommended, thus minimizing phenylalanine and tyrosine intake. Vitamin C has been shown to slow down conversion of homogentisate to polymer deposits in the skin. Finally, nitisinone has been shown to halt ochronosis in mice ⁷.

Complications

• aortic stenosis ⁴

• spontaneous tendon ruptures have been reported ³

• deposition in heart and kidneys can lead to cardiac and renal failure

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:

• calcium pyrophosphate deposition disease (CPPD): mainly extravertebral

There is a broad differential for intervertebral disc calcification.

See also

• polyarticular arthropathy