Alkaptonuria (AKU) is a rare and serious genetic disease. It affects 1 in 500,000 in the UK. AKU is caused by a recessive gene that leads to a missing enzyme. This means that patients are unable to metabolise correctly an amino acid, tyrosine, and instead produce homogentisic acid (HGA) at 2,000 times the normal rate. HGA is a black pigment that binds to cartilage, destroying it and causing severe early-onset osteoarthritis. It accumulates in the prostate and kidney, causing stones; in the heart, causing heart disease; in the eyes, causing black spots; and in the urine, turning it black. As it also turns bones black, AKU is known as black bone disease. It was the first genetic disease ever described, by Sir Archibald Garrod, in London, 110 years ago, in 1901. There is still no cure.

The AKU Society is a patient group, designed to unite all people affected by AKU, patients, their families and their doctors. While we are primarily a UK-based group, as we were the first AKU Society in the world, we have a far-reaching effect. We have helped several sister charities to form, including ALCAP (French AKU Society), AIMAKU (Italian AKU Society) and AKU Society North America (USA and Canada AKU Society), with plans for upcoming organisations in Slovakia, Jordan and the Netherlands.

AKU patients, like all rare disease patients, often feel isolated because of their disease. Many patients have had years of misdiagnosis and misunderstanding by the medical profession. Often, their family find it hard to understand what is wrong. This leaves many AKU patients feeling depressed and with a sense of hopelessness. The AKU Society tries to change this, by bringing patients together. Projects such as Rare Disease Communities (in collaboration with EURORDIS, the European organisation for rare diseases), the Route Maps project (in collaboration with the Genetic Alliance UK), and our annual patient workshops help build a feeling of a wider community. We actively encourage patients to help one another, to impart the best methods to cope with a rare disease.

The AKU Society also promotes research into the understanding and treatment of AKU. We firmly believe that the best way to help patients is to cure the disease. That can only be achieved by recruiting the scientists and clinicians dedicated to our cause. We have built strong partnerships with several universities and hospital trusts that have helped expand scientific knowledge of AKU that one day will be used to cure the disease.

ACHIEVEMENTS AND PERFORMANCE DURING THE PERIOD

One of our largest projects has been the patient information scheme. To date we have identified 601 people with AKU worldwide: UK 80, Slovakia 208, other Europe (including Turkey) 94, North America 92, Central and South America 5, Australia 11, Middle East Asia 95, South East Asia (including China and Japan) 2, South Asia (including India) 12, and Russia 2. A paper explaining how we located the AKU patients was recently published by our medical director, Dr Ranganath of the Royal Liverpool University Hospital. (Ranganath L et al. Identification of alkaptonuria in the general population: a United Kingdom experience describing the challenges, possible solutions and persistent barriers. Journal of Inherited Metabolic Disorders 2011)

We held our 4th International Workshop on AKU at Sidney Sussex College, Cambridge, on 10-11 January 2011. It was a tremendous success, bringing together 80 AKU scientists and clinicians from 10 different countries. The two days of scientific presentations on the latest work in AKU research also gave time for lengthy discussions on the future of AKU work and allowed the AKU Society to plan for the next year.

We have significantly scaled up our research. We are in the middle of a Big Lottery Fund grant to finance a multi-disciplinary team at the University of Liverpool. The team has already created an animal model and human cell model of AKU (Tinti L et al. Development of an in vitro model to investigate joint ochronosis in alkaptonuria. Rheumatology 2011) They are now looking at the local metabolomics changes seen in AKU with an eye to develop novel biomarkers to better screen for AKU-associated damage to the cartilage and bone.

The Royal Liverpool University Hospital completed a clinical evaluation study of 20 adult AKU patients, the results of which have helped the clinical research team to develop AKU severity score index (Cox TF et al. A quantitative assessment of alkaptonuria: Testing the reliability of two disease severity scoring systems. Journal of Inherited Metabolic Disorders 2011). The severity score index will be an invaluable tool to help us design a future clinical trial in AKU.

Partnerships

The AKU Society works in close partnership with several organisation, most notably the University of Liverpool (with Prof Jim Gallagher and his lab at the Department of Human Anatomy and Cell Biology, and Dr Dom Williams and his lab at the Department of Pharmacology) and the Royal Liverpool University Hospital (with Dr L Ranganath at the Department of Clinical Chemistry). The AKU Society was founded in Liverpool, so our links there are the strongest; however, we have formed several other partnerships:

- The University of Cambridge, with Dr Melinda Duer at the Department of Chemistry. Her department has been studying the microscopic structure of AKU damaged cartilage and recently published its work in the JIMD. (Chow WJ et al. Collagen atomic scale molecular disorder in ochronotic cartilage from an alkaptonuria patient, observed by solid state NMR. Journal of Inherited Metabolic Disorders 2011)