Treatments
There is no cure for Alkaptonuria: no way of preventing people getting it, and no way of curing people who have it. At present the best outlook for Alkaptonuria sufferers is early detection followed by management and treatment of symptoms.
The key area is managing and treating the joint deterioration caused by build-up of homogentisic acid in the cartilage and bone. Close attention to control of joint pain is critically important. Inadequate pain control may lead to limited use of the affected joint, further reducing the range of motion in that joint. The use of a regular basis of a long-acting non-steroidal anti-inflammatory medication, in combination with a more potent short-acting medication for periods of increased pain, can be beneficial.
Physical and occupational therapy are important to maintain muscle strength and flexibility. A programme involving swimming or pool physical therapy is ideal, since this puts less stress on the joints. Avoiding manual labour or high impact sports, which can stress the spine and large joints, may help delay the progression of arthritis. Joint replacement surgery is an option available for significant arthritis, and is generally performed with the goal of pain relief rather than increased mobility.
After age 40, patients should be monitored for possible heart complications related to Alkaptonuria. An echocardiogram can detect aortic or mitral valve calcification and a CT scan of the chest can detect coronary artery calcification.
Kidney and prostate stones can also occur in individuals with Alkaptonuria and may require surgery.
There is no clinically proven treatment available to prevent or reverse the pigmentary changes (ochronosis) seen in Alkaptonuria.
Dietary treatments
There are anecdotal reports that a diet low in protein – especially in amino acids, phenylalanine and tyrosine – can help delay joint problems. However, there have been no formal clinical trials and there is no proof that such a diet is of any benefit. Maintaining a low-protein diet in order to restrict these amino acids is also extremely difficult to do.
Some Alkaptonuria sufferers take vitamin C as an anti-oxidant. However, this has not been shown to have any impact on the damage to cartilage caused by homogentisic acid. In guinea pigs induced to have Alkaptonuria by feeding them large amounts of tyrosine, the anti-oxidant vitamin C apparently prevents Alkaptonuria. However, vitamin C has no proven effect on the hereditary type of Alkaptonuria in humans.
Trials of a new drug
Some hope is offered by a new drug that is a potential treatment for Alkaptonuria. Nitisinone, or NTBC, is a herbicide which causes plants to bleach. It inhibits the enzyme which produces homogentisic acid. Short-term studies have shown that the amount of homogentisic acid in the urine of patients with Alkaptonuria is reduced by up to 95% when taking Nitisinone.
The National Institutes of Health in the USA began a three-year clinical trial of Nitisinone in April 2005. Unfortunately, the results were inconclusive. It looks like more work needs to be done before it is adapted for use in AKU.
Nitisinone is currently approved for use in tyrosinemia type I, a severe liver disease in infants and children, but not for Alkaptonuria. The possible side-effects are related to the elevated tyrosine levels that occur with the use of NTBC. This could lead to eye complications, such as sensitivity to light and crystal formation in the cornea. There have been no reports of permanent eye damage. For a more complete look at Nitisnone, please read the report written by an AKU patient, Dr Duncan Batty.
As Nitisinone is licensed from another disease, AKU patients can take Nitisinone off-label. This means that they have discussed the idea with their GP and have agreed to try the drug, with the knowledge that it is not licensed for AKU. To read testimonies from a handful of patients taking Nitisinone off-label, please click here. If you are a patient, or a doctor and are interested in knowing more about Nitisinone, please contact us at info@akusociety.org