What Happens in Alkaptonuria?

Reviewed on 2/3/2021

Alkaptonuria is a type of metabolic disorder. Amino acids are the building blocks of proteins. They are usually broken down in the body in a series of chemical reactions. In alkaptonuria, however, a substance called homogentisic acid is produced that cannot be broken down any further. This happens because the enzyme that normally breaks it down does not work properly. The affected individuals may have dark urine, or their urine may turn black on exposure to air. Other characteristics of alkaptonuria are as follows:

  • Alkaptonuria is a rare inherited disorder that prevents the body from fully breaking down two amino acids: tyrosine and phenylalanine.
  • Alkaptonuria results in a buildup of a chemical called homogentisic acid in the body.
  • This can impart urine and parts of the body a dark color and lead to a range of problems over time.
  • It happens when our body cannot produce enough homogentisate dioxygenase (HGD) enzyme to break down the homogentisic acid, which is toxic to the body.

Cause:

Alkaptonuria is caused by changes in genes or mutations, especially in the homogentisate 1,2-dioxygenase gene. This is acquired when the parents have these genes that are passed into their child.

What are the signs and symptoms of alkaptonuria?

One of the earliest signs of this condition is dark-stained nappies because homogentisic acid causes the urine to turn black when exposed to air for a few hours. If this sign is missed or overlooked, the disorder may go unnoticed until adulthood because there are usually no other noticeable symptoms until the person reaches their late 20s to early 30s. Other signs and symptoms may include:

  • Arthritis (pain and inflammation in the joints)
  • Darkening of the ear (or other parts of the skin) (An obvious sign of alkaptonuria in adults is thickening and blue-black discoloration of the ear cartilage. This is called ochronosis. The earwax may also be black or reddish-brown.)
  • Dark spots on the sclera (the white of the eye)
  • Presence of dark urine
  • Severe back pain
  • Deposits of homogentisic acid around the heart valves can cause them to harden and turn brittle and black (The blood vessels can also stiffen and weaken, and this can lead to heart disease and may require heart valve replacements.)
  • Deposits that can also lead to kidney stonesbladder stones, and prostate stones

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How is alkaptonuria treated?

There is no cure for alkaptonuria. However, Nitisinone and vitamin C has shown some promise. Painkillers and lifestyle changes may help cope with the symptoms. The condition may be managed using the following methods:

  • Some individuals may benefit from high doses of vitamin C. Vitamin C has been shown to slow arthritis development and reduce the buildup of the dark pigment in urine.
  • Nitisinone reduces the homogentisic acid level in the body. It's currently an experimental treatment, but research into its effectiveness is ongoing and there have been some promising results so far.
  • Dietary restriction of amino acids: phenylalanine and tyrosine. Food items such as meat products, soy products, milk products, certain types of artificial sweeteners, and nuts should be avoided.
  • Speak to a doctor about painkillers and other techniques to manage pain.
  • Regular gentle exercise can help by building muscle and strengthening the joints. Exercise is also good for relieving stress, losing weight, and improving posture, all of which can ease the symptoms.
  • Sometimes, surgery may be necessary if the joints are damaged and need replacing or if the heart valves or vessels have hardened.

How is the outlook in patients with alkaptonuria?

Patients with alkaptonuria have a normal life expectancy but with a lesser quality of life. Life expectancy is not significantly reduced. However, pain can be constant, and progressive functional decline is observed with a loss of mobility. Patients often require the use of physical aids (crutches and wheelchair). Cardiac complications are often life-threatening and may worsen the prognosis.

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References
Mistry JB, Bukhari M, Taylor AM. Alkaptonuria. Rare Dis. Published online December 18, 2013. doi:10.4161/rdis.27475

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