Alkaptonuria: Year of the Zebra

Alkaptonuria is a rare genetic metabolic disorder that causes a deficiency in the homogentisate 1,2 dioxygenase, or HGD, enzyme and is characterized by the accumulation of homogentisic acid, or HGA, in the body. Alkaptonuria is inherited in an autosomal recessive pattern, meaning that two copies of the defective gene are required to cause the disorder. Normally, HGA is converted, by the HGD enzyme, within the body and used for cellular processes. In alkaptonuria, the absence of the HGD enzyme leads to excess HGA being turned into hyperpigmented substances that accumulate in various tissues.

Now, alkaptonuria most commonly presents with manifestations in the urine, skin, and joints from HGA accumulation. The most common symptom is the presence of dark brown or black urine. Excess HGA that gets excreted in the urine is then exposed to the air, which can turn the urine black after time. In affected infants, this may appear as black stains in diapers.

In the skin, blue-black areas of hyperpigmentation appear, usually on ear cartilage or sclera of the eye. These hyperpigmented areas are called ochronosis.

Lastly, in the joints, arthritis occurs, most commonly the low back, hips, knees, and shoulders, and leads to pain and decreased joint mobility.