Taking on the world's first genetic disease

摘要

Alkaptonuria (AKU) was the first genetic disease ever identified, by Sir Archibald Garrod in 1901. More than 100 years later, AKU still has no cure, nor treatment. AKU is a serious, autosomal recessive, multisystem disorder of peak adulthood affecting approximately one in every 250,000 people, although this figure can rise to one in 19,000 in certain countries such as Slovakia2. A recent study of 44 AKU patients, showed 76 joint replacements, 28 ruptures (tendons/ ligaments/muscle), 10 fractures, four with renal stones, four with prostatic stones and seven with aortic valve disease3. This morbidity is caused by increased homogentisic acid (HGA) due to a deficient enzyme, homogentisate 1,2-dioxygenase (HGD), despite efficient urinary excretion. The absence of HGD results in patients being unable to fully metabolise the amino acid tyrosine. Tyrosine is broken down via HGA, which in unaffected individuals is then converted to acetoacetate and fumarate, via maleylacetoacetate, in the liver.