Alkaptonuria

Abstract

Alkaptonuria (AKU) is a rare disorder of autosomal recessive inheritance. It is caused by a mutation in a gene that results in the accumulation of homogentisic acid (HGA). Characteristically, the excess HGA means sufferers pass dark urine, which upon standing turns black. This is a feature present from birth. Over time patients develop other manifestations of AKU, due to deposition of HGA in collagenous tissues, namely ochronosis and ochronotic osteoarthropathy. Although this condition does not reduce life expectancy, it significantly affects quality of life. The natural history of this condition is becoming better understood, despite gaps in knowledge. Clinical assessment of the condition has also improved along with the development of a potentially disease-modifying therapy. Furthermore, recent developments in AKU research have led to new understanding of the disease, and further study of the AKU arthropathy has the potential to influence therapy in the management of osteoarthritis.

Keywords: alkaptonuria; homogentisate 1,2 dioxygenase; homogentisic acid; ochronosis; ochronotic arthropathy; osteoarthritis.

Figure 1. Adapted from reference . The diagram illustrates the normal phenylalanine and tyrosine degradation pathway, enzymes involved and defects that can occur (highlighted blue). The metabolism of HGA occurs in the liver, and HGD is an enzyme expressed in this organ.

Figure 2. Taken from reference . The map illustrates the current number of AKU patients identified worldwide.