The New England Journal of Medicine has published a clinical image case on alkaptonuria, a rare inherited metabolic disorder that causes a dark pigment to build up in body tissues over a lifetime.
The journal posted the case to its Images in Clinical Medicine series, tagging it under rheumatology — the branch of medicine dealing with joints, bones and connective tissue. Alkaptonuria (also called AKU, or black bone disease) is caused by the body’s inability to fully break down two amino acids, phenylalanine and tyrosine, leading to a build-up of homogentisic acid in cartilage, tendons and other tissues.
The condition is exceptionally rare. According to the National Institute for Health and Care Excellence, it affects roughly one in every 250,000 to 1,000,000 people. Symptoms often go unnoticed for decades — the first visible sign for many patients is urine that darkens on exposure to air, sometimes noticed in infancy. Joint pain and stiffness, resembling arthritis, typically develops in adulthood.
There is no cure.
Nitisinone, a drug originally developed for a different metabolic disorder, is used off-label in the UK to slow the accumulation of homogentisic acid; it does not hold a UK marketing authorisation for AKU and is accessed through specialist metabolic services on an off-label basis. The AKU Society, a UK-based patient charity, runs a dedicated centre of excellence at the Royal Liverpool University Hospital — one of the world’s only specialist AKU clinics.
Because symptoms mimic common conditions such as osteoarthritis, diagnosis is frequently delayed by years. The NHS advises anyone with unexplained joint deterioration, darkening of ear cartilage, or urine that turns dark when left to stand to speak to their GP and mention the possibility of a rare metabolic condition.
Key information
- AKU Society helpline: contact via the AKU Society directly for patient support and specialist referral guidance
- GP referral: ask your GP about testing for homogentisic acid in urine if symptoms match
- NHS 111: call 111 for non-emergency health advice
- Royal Liverpool University Hospital: hosts one of the world’s only specialist AKU clinics; NHS-funded referrals are available for confirmed patients from England and Scotland, while patients from Wales and Ireland may require local funding arrangements
Source: @NEJM