Hereditary ochronosis, Homogentisic acid oxidase deficiency
Alkaptonuria (AKU), also known as ‘Black Bone Disease’, is a rare genetic disease which causes severe, early onset osteoathritus. It is caused when an enzyme called homogentisic dioxygenase (HGD) is faulty so is unable to break down a toxic acid called HGA. Although some HGA is removed from the body in urine, HGA builds up in the body of AKU patients at 2,000 times the normal rate. The accumulation of HGA can lead to debilitating health problems in adult AKU patients.
When the urine of an AKU patient is exposed to the air, it darkens and eventually goes black due to the high concentration of HGA. Parents often first become aware that there may be a problem when they discover black urine in their baby’s nappies. Black urine does not cause any medical problems, and it is the only symptom of AKU present in children until they reach their twenties. It is not clear why other symptoms don’t present themselves until adulthood.
HGA builds up in the connective tissue of the body, which causes bones and cartilage to blacken and become brittle. This process is called ochronosis. Patients often report their first joint problems and back pain in their 20s and 30s. Ochronosis causes several other symptoms of AKU such as discoloration of the ears and black spots in the eyes.
Other symptoms of AKU include kidney, prostate and bladder stones, black or dark sweat and a blue speckled discolouration of the skin. HGA can cause blood vessels and valves in the heart to turn black and brittle, leading to heart problems in some patients. Heart disease due to the hardening of blood vessels and valves in the heart is the only potentially fatal consequence of AKU, however it is thought to be an uncommon symptom of AKU. The life expectancy of AKU patients is not significantly reduced compared to the general population, however there is a progressive decline in mobility as patients age.
It has been demonstrated that a drug called nitisinone, which is currently licensed for the treatment of tyrosinaemia type 1, can reduce the levels of HGA by up to 95%. Clinical trials to test whether nitisinone is effective at preventing ochronosis are currently ongoing. You can find out more about the DevelopAKUre clinical trials at http://www.developakure.eu/ .
source: AKU society