Impact of chronic kidney disease on the natural history of alkaptonuria

Abstract

In alkaptonuria, deficiency of homogentisate 1,2-dioxygenase leads to the accumulation of homogentisic acid (HGA) and its metabolites in the body, resulting in ochronosis. Reports of patients with alkaptonuria who have decreased kidney function are rare, but this seems to play an important role in the natural history of the disease.We describe a 68-year-old female with chronic kidney disease (CKD) of unknown etiology who started peritoneal dialysis (PD) after 5 years of follow-up and who was diagnosed with alkaptonuria at this time. Progressive exacerbation of ochronotic manifestations had been noted during these last few years, as kidney function worsened. After PD initiation, the disease continued to progress, and death occurred after one year and a half, due to severe aortic stenosis-related complications. Her 70-year-old sister was evaluated and also diagnosed with alkaptonuria. She had no renal dysfunction. Higher HGA excretion and significantly milder ochronosis than that of her sister were found.We present two alkaptonuric sisters with similar comorbidities except for the presence of CKD, who turned out to have totally different evolutions of their disease. This report confirms that kidney dysfunction may be an important factor in determining the natural history of alkaptonuria. © 2012 The Author.