Alkaptonuria is an inherited condition that causes arthritis, kidney stones, spots of dark pigmentation, and dark urine. Ochronosis, a buildup of dark (blue-black) pigment in certain tissues, is a characteristic feature of alkaptonuria. The first symptom of alkaptonuria is often urine that turns black or very dark when it is exposed to air (oxidation). However, this color change may not occur immediately after urination.

Variants (also called mutations) in the HGD gene cause alkaptonuria. The HGD gene provides instructions for making an enzyme called homogentisate 1,2-dioxygenase. This enzyme helps break down the amino acids phenylalanine and tyrosine, which are important building blocks of proteins. Phenylalanine and tyrosine are broken down when they are no longer needed or when there are too many of them.

Alkaptonuria is rare, affecting 1 in 250,000 to 1 million people in the United States. Alkaptonuria is more common in certain areas of Slovakia (where it has an incidence of about 1 in 19,000 people) and in the Dominican Republic.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

Published Date: March 10, 2025
Published By: National Institutes of Health