What is alkaptonuria? The rare disease that turns your pee black

The mid-section of a person is shown as they are sat on the toilet holding a roll of toilet paper. — Patients with alkaptonuria have dark-stained connective tissues and black urine because a genetic mutation causes an enzyme involved in protein metabolism to malfunction. (Image credit: Antonio Hugo Photo via Getty Images)

Disease name: Alkaptonuria, also known as "black urine disease"

Affected populations: The exact prevalence of alkaptonuria worldwide is unknown. However, estimates suggest that the disease affects between 1 in 250,000 and 1 in 1 million people in the U.S. More than 1,000 cases of alkaptonuria have been reported in the medical literature. Individuals from any group can potentially develop the disease, regardless of their sex, race or other factors. However, alkaptonuria is a recessive genetic disorder, meaning people will only develop it if they inherit two faulty copies of a specific gene — one from each of their parents.

Causes: People with alkaptonuria are unable to fully break down all the building blocks of proteins that they consume or that their body makes. This is because a mutation in a gene called homogentisate 1,2-diooxygenase (HGD) causes an enzyme that normally does the job to malfunction. Consequently, a chemical called homogentisic acid accumulates in different tissues in the body, especially in connective tissues, such as cartilage.

Symptoms: One of the earliest signs that someone has alkaptonuria is dark stains in their diapers as babies, because the homogentisic acid in their urine turns black upon exposure to air.

Besides dark urine, people with alkaptonuria often have no other noticeable symptoms of the disease until they are in their late 20s or early 30s.

Over time, homogentisic acid continues to build up in a person's tissues, staining those tissues a slate blue or black color and eventually weakening and damaging them. This can lead to severe deformities in the joints and spine, as well as organ dysfunction, including issues with the kidneys and heart. Symptoms of alkaptonuria tend to be more severe and come on sooner in males than in females.

A close-up photo of a patient with alkaptonuria who has dark patches of skin around their mouth. — Darkened patches of skin on the face of a patient with alkaptonuria. (Image credit: Universidad CES, CC BY 3.0 https://creativecommons.org/licenses/by/3.0/deed.en, via Wikimedia Commons, image presented against dark background.)

Although patients with alkaptonuria tend to have a normal life expectancy, the disease can markedly impact their quality of life.