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.
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 estimated incidence is around 1:250,000-1,000,000 3,5.
Patients often have pigmentation of auricular cartilages and sclera. Urine colour 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.
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).
A defective gene has been mapped to chromosome 3q21–q23 5.
The most well-described features are those involving the skeletal system.
- severe osteoporosis
- multilevel intervertebral disc calcification: tends to be widespread (and involves nucleus pulposus)
- syndesmophyte formation
- multilevel disc space narrowing
- symmetrical or asymmetrical joint space loss: early osteoarthritis
- subchondral sclerosis
Treatment and prognosis
There is currently (as of February 2018) no effective treatment for ochronosis.
- aortic stenosis 4
- spontaneous tendon ruptures have been reported 3
History and etymology
Ochronosis was defined by Virchow, who histologically described the connective tissue in alkaptonuria, given the cartilage's ochre (yellow) hue under the microscope.
For skeletal radiographic manifestations consider:
- calcium pyrophosphate deposition disease (CPPD): mainly extravertebral
There is a broad differential for intervertebral disc calcification.
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- 3. Manoj kumar RV, Rajasekaran S. Spontaneous tendon ruptures in alkaptonuria. J Bone Joint Surg Br. 2003;85 (6): 883-6. J Bone Joint Surg Br (link) - Pubmed citation
- 4. Ffolkes LV, Brull D, Krywawych S et-al. Aortic stenosis in cardiovascular ochronosis. J. Clin. Pathol. 2007;60 (1): 92-3. doi:10.1136/jcp.2005.032417 - Free text at pubmed - Pubmed citation
- 5. Roser M, Möller J, Komoda T et-al. Alkaptonuric aortic stenosis. Eur. Heart J. 2008;29 (4): 444. doi:10.1093/eurheartj/ehm406 - Pubmed citation
- 6. Kruithof E, Baeten D, Veys EM et-al. Case Number 29: Ochronosis: synovial histopathological characteristics. Ann. Rheum. Dis. 2004;63 (2): 130. doi:10.1136/ard.2003.013912 - Free text at pubmed - Pubmed citation