1.Why has it taken so long for any studies to be carried out on Alkaptonuria and its degenerative nature? Does anyone else suffer with eczema on their joints, especially back of knees?
There are several reasons contributing to the rarity of research carried out on Alkaptonuria. It is a rare disease with an incidence of 1 in 250,000 to 1 in 1,000,000. Many physicians will never see a patient with alkaptonuria in their career. The rarity also makes it difficult to obtain a large enough number of patients to carry out controlled studies. Lack of funding for rare diseases is another factor.

Eczema is a common skin condition in the general population and is not related to alkaptonuria.

It is not seen at an increased rate in individuals with alkaptonuria.

2. Do any of the male AKU patients suffer with Prostate stones and if so what treatment do they have?
Prostate stones are seen fairly frequently in patients with alkaptonuria. The treatment is similar to that of prostate stones resulting from other causes. If the stones are large enough to cause obstruction of the urinary flow, they may require surgery. A urologist can help make that determination

3. My sister (Who has not been diagnosed with AKU yet), would like to know at what age does the signs of AKU start in women, i.e. Back trouble, stones etc..?
In general patients, both male and female mention back pain starting in their twenties and thirties. The signs of alkaptonuria in women may present later than in males depending on the amount of weight-bearing and joint stress an individual has had. Many of the other signs seen in alkaptonuria such as stones, eye and ear pigment changes, heart valve involvement occur at similar ages in men and women. However, even in the same family, siblings often have different levels of severity and age at presentation.

4. Are there any AKU patients out there who have unaffected siblings as my sister has not been tested as she is afraid that she may have it?
A patient with alkaptonuria may have unaffected siblings.

Alkaptonuria is passed on from an individuals mother and father in an autosomal recessive pattern. This means that each parent is a carrier of the gene change that can cause alkaptonuria.

If a child receives the gene with the disease causing change from both parents, he or she will have alkaptonuria; there is a 1 in 4 or 25% chance of this occurring with each pregnancy.

A child could receive the gene that doesn’t have an alkaptonuria causing change from both parents, he or she will not have alkaptonuria and isn’t a carrier; there is a 1 in 4 or 25% chance of this occurring with each pregnancy.

The last possibility is that a child receives the gene with a disease causing change from on parent and the gene without a disease causing change from the other, he or she will be a carrier similar to the parents; there is a 1 in 2 or 50% chance of this occurring with each pregnancy.

5. At what general age do the hip, knee and shoulder joints start to deteriorate and need replacing?
In general people start complaining of knee pain in their forties. Hip and shoulder pain often occurs later, but usually by fifties. Many people have at least one joint replaced by age 55.

6. Are there any AKU sufferers out there who have affected children?
This is possible, but very unlikely due to the rare occurrence of alkaptonuria. It would mean that a person with alkaptonuria would have to have children with an individual whom is either a carrier for the disease or has alkaptonuria themselves.

7. Does every AKU patient develop dark pigmentation of the eyeball?
Eventually all patients will develop the characteristic pigment changes. There is dark brown to black pigment accumulating in the white part of the eye at the position where tendons of the eye muscles attach to the eyeball. The amount of pigmentation can vary, often it is seen starting in the 4th or 5th decade, however in some individuals it might not be apparent until much later.

8. Does every AKU patient develop dark pigmentation of the skin and if so, which areas are commonly affected?
The onset of pigmentation of the skin is often at similar ages to the pigmentation of the eyes. It can also vary, being more visible in some patients than others. It is often first seen in the ear lobe. We have also seen people with alkaptonuria that have pigmentation of the bridge of the nose, cheeks, hands, and skin overlying tendons.

9. What is the ratio between male and females who have the disorder?
They are roughly equal.

10. How long, roughly will it take before the NTBC drug will be safe for use?
There is clinical trial in progress at the National Institutes of Health, Bethesda, MD, USA. It is a clinical trial looking at the benefit of NTBC in retarding progression of joint disease in patients with alkaptonuria. The study is designed to last 3 years. After the study is finished, it would probably take some time to get NTBC approved for clinical use in patients with alkaptonuria, it could be up to 4 or 5 years from now before NTBC is available, this is if the trial shows that the drug is safe for use and does help with the joint problems.

11. Will NTBC halt the production of HGA altogether or just reduce the amount produced?
NTBC blocks the enzyme that helps form HGA. Short-term studies have shown that the amount of HGA in the urine of patients with alkaptonuria is reduced by up to 95% when taking NTBC.

12. When NTBC is given the OK, will it be accessible to everyone throughout the world or just certain countries?
This is certainly our goal, however this would also be up to the drug approval process of each country.

13. Do males have bladder problems, other than the stones?
Several males have problems with urinary tract infections and urinary urgency and frequency probably related to obstruction from prostate stones.

14. Do all AKU sufferers suffer with raptured tendons, in legs, or is it just a freak occurrence?
Not all people with alkaptonuria have ruptured tendons, but they do occur often enough in AKU to be more that “just a freak occurrence”. The most frequent rupture site is the Achilles tendon. We have seen both males and females with Achilles tendon ruptures, but they may occur slightly more frequently in males. This may be related to activity and sports.

15. Does anyone else suffer with memory problems?
Alkaptonuria is not known to be associated with memory problems. Memory problems can have many causes, if an individual with alkaptonuria has this type of complaint, they should have a thorough consultation with a neurologist.

16. Does anyone else suffer with memory problems? (Just a joke!)
You did get a smile!

17. At what age do the heart problems start and what is involved?
The heart problems often start after age 50. The findings can include calcification of the coronary arteries (the vessels that feed the heart), this can be seen by computed tomography (CT) or magnetic resonance imaging (MRI). Often aortic, and less commonly, mitral valve involvement occurs. These are heart valves that separate chambers of the heart. There can be calcium deposits on the valves causing narrowing (stenosis) of the valve causing problems with blood flow. The valve changes can be seen by echocardiography. It is suggested that patients with alkaptonuria be evaluated for heart problems starting before age 50.

18. Are there any special dietary needs that need to be taken into account? If so what are they?
There are no specific dietary recommendations for patients with alkaptonuria. It is suggested that a low protein diet may help delay joint problems, there are anecdotal reports to this, but no formal clinical trials. At the NIH we have observed several patients who were vegetarians or restricted their protein intake, on average they had similar onset of joint and pigmentation problems.

19. Has anyone else been taking the Ascorbic Acid (Vit C) and if so have you had any side effects?
We have seen a fairly large number of patients taking vitamin C, despite long-term use, in some people since childhood, they have similar joint problems to other patients with alkaptonuria. We have not seen any side effects, however there is some suggestion that very high doses of vitamin C may contribute to renal stone formation, this has not be evaluated formally in patients with alkaptonuria.

20. Has anyone else tried any other diets that has helped them manage their AKU successfully?
It is unlikely that diet modification will have a major impact on the course of the joint problems in alkaptonuria.