Alcaptonuria: What is it? History, Causes, Symptoms, Complications, Diagnosis and Treatment

Also known as endogenous ochronosis, it is a very atypical congenital disease.

It is characterized by the dark color that urine takes when it comes into contact with air.


In 1859 the term “alcapton” was used for the first time to describe the urinary reducing compound of a patient, later identified as homogentisic acid.

A complete review of the cases of alcaptonuria worldwide until 1967 showed that approximately 600 points had been described so far, thus estimating that the current incidence of alcaptonuria is 1 case in 250,000.

Thanks to the molecular analyses carried out recently, 23 new mutations of the HGD gene were identified, elevating them to 67. It is believed that one of these mutations (M368V) has spread through Europe with the past migrations.

Slovakia and the Dominican Republic have proved to be hot spots for the mutation of this gene, so in these countries, the alcaptonuria is very frequent.


This disease is acquired in a hereditary way. It originates thanks to a deficiency of the HGD gene (homogentisate dioxygenase), an enzyme that allows determining the accumulation of homogentisic acid in the blood and urine.


The deficiency of this enzyme causes the body not to be able to adequately decompose certain amino acids such as tyrosine and phenylalanine, causing homogentisic acid to accumulate in the urine and tissues of the body.

This acid is expelled through the urine, and it darkens due to the oxidation of the acid when exposed to air.


In some cases, the alcaptonuria is already entering an advanced age (40 years onwards). Although many people do not present symptomatology apart from the darkening of the urine, there are specific symptoms that could also appear:

• Progressive arthritis, especially in the spine.

• Darkening of the cartilage of the ear.

• Dark spots on the sclera and the cornea.

• Prostatitis .


Patients of alcaptonuria, on some occasions, can present complications such as kidney stones, coronary artery disease, arrhythmias, respiratory failure, and even homogentisic acid can accumulate in the valves of the heart, generating the need to perform a valvuloplasty.


There are several ways to diagnose a patient with alcaptonuria, such as sequencing the HGD gene and urine chromatographic analysis.

However, the first phase of the diagnosis is generated based on clinical suspicion and then proceeds to a urinalysis, where we measure the levels of homogentisic acid in the urine.

The genetic test is performed after the diagnosis to confirm it.


Life expectancy is not affected, but pain can often be constant, and part of the mobility can be lost.

Cardiac complications also pose a threat and could worsen the prognosis.


The treatment of this disease is palliative; that is, it only seeks to improve the patient’s quality of life.

A low-protein diet, medical therapy with non-steroidal anti-inflammatory drugs, and physiotherapy are recommended, which will help improve the patient’s pain and articulation.

Surgery would be recommended in some people of more advanced ages if the pain became very severe to replace joints in the knees or hips.

However, the most used treatment is the consumption of vitamin C, which is used to reduce the accumulation of brown pigment in the cartilage and to reduce the development of arthritis; however, in many cases, it has had unsatisfactory results.