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Alkaptonuria

Last updated April 18, 2018

Approved by: Krish Tangella MD, MBA, FCAP

Universidad CES

Accumulation of homogentisic acid in connective tissues on the face associated with alkaptonuria.


What are the other Names for this Condition? (Also known as/Synonyms)

  • AKU (Alkaptonuria)
  • Alcaptonuria
  • Homogentisic Acid Oxidase Deficiency Disorder

What is Alkaptonuria? (Definition/Background Information)

  • Alkaptonuria (AKU) is a rare genetic disorder that causes urine to turn dark black, when exposed to the air
  • Mutations in the HGD gene cause AKU. When this mutation is present, the body is unable to correctly break down amino acids such as tyrosine and phenylalanine
  • This leads to homogentisic acid build up in the body, which is excreted in urine. When homogentisic acid is exposed to air, it turns to dark black color, as seen in individuals with Alkaptonuria
  • Although the disorder is present since birth, many people with AKU are not diagnosed until they are in their 30s to 40s, when defining symptoms arise
  • Most individuals with Alkaptonuria not only suffer from darkly pigmented urine, but also experience arthritis, darkening of the ear, and even dark spots on the eye
  • The possible complications of Alkaptonuria include arthritis, abnormalities of the heart valve and kidney, and prostate stones
  • While there are currently no preventative measures against Alkaptonuria, individuals can undergo treatment to help with their symptoms. Overall, the prognosis of Alkaptonuria is good

Who gets Alkaptonuria? (Age and Sex Distribution)

  • Alkaptonuria is present at birth, although most symptoms do not arise until mid-adulthood
  • It affects both men and women
  • AKU is rare worldwide, affecting 1 in 250,000 to 1 in a million people
  • It is found with a higher frequency in certain areas of Slovakia and Dominican Republic

What are the Risk Factors for Alkaptonuria? (Predisposing Factors)

The risk factors of Alkaptonuria include:

  • Family history of the condition: Alkaptonuria is a genetic disorder inherited in an autosomal recessive pattern. This means that the mutation must be inherited from both parents in order to inherit the disorder and manifest the signs and symptoms of Alkaptonuria
  • If the individual only inherits one copy of the mutated gene, they will be a carrier of AKU and will not manifest the disorder 

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider. 

What are the Causes of Alkaptonuria? (Etiology)

Alkaptonuria is a rare disorder that is caused by mutations in the HGD gene. It is an autosomal recessive condition.

  • Normally, the HGD gene codes for the instructions to make the enzyme homogentisate oxidase. This enzyme helps break down phenylalanine and tyrosine, which then serve as building blocks for many proteins
  • If mutations are present, then homogentisate oxidase is not correctly synthesized. As a result, homogentisic acid builds up in the body
  • If too much of this acid accumulates, it gets deposited in the connective tissues, leading to darkening of the skin and cartilage of the body. Overtime, too much build up will cause arthritis
  • To reduce buildup, homogentisic acid is excreted in the urine. When this occurs, it causes the urine to turn dark on exposure to air

What are the Signs and Symptoms of Alkaptonuria?

The common signs and symptoms of Alkaptonuria include:

  • Arthritis: Pain and inflammation in the joints
  • Darkening of the ear (or other parts of the skin)
  • Dark spots on the eye (sclera and cornea, the whites of the eye)
  • Presence of dark urine
  • Chronic back pain

How is Alkaptonuria Diagnosed?

The diagnosis of Alkaptonuria may involve:

  • A complete evaluation of medical history and a thorough physical exam
  • A urine test is performed to diagnose Alkaptonuria. Ferric chloride is added to the urine sample, which turns to black color, if the affected individual has Alkaptonuria
  • Urinalysis to detect homogentisic acid using gas chromatography
  • Molecular DNA testing to detect mutations in the HGD gene

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis. 

What are the possible Complications of Alkaptonuria?

The possible complications of Alkaptonuria include:

  • Arthritis
  • Heart valve conditions: Longstanding AKU can cause calcification of the heart valves and coronary arteries, which can result in abnormal functioning of the heart, and even result in heart attacks
  • Coronary artery disease
  • Kidney stones causing blood in urine and low back pain
  • Prostate stones causing urinary difficulties

How is Alkaptonuria Treated?

There is no cure for Alkaptonuria. 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 decrease the buildup of dark pigment in urine
  • Dietary restriction of amino acids phenyalanine and tyrosine. Food items, such as meat products, soy products, milk products, certain types of artificial sweeteners, and nuts, should be avoided

How can Alkaptonuria be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Alkaptonuria, since it is a genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Alkaptonuria? (Outcomes/Resolutions)

  • Individuals with Alkaptonuria are usually able to lead normal lives
  • Most symptoms do not arise until the individuals are in their mid-30s and 40s. Nevertheless, the prognosis associated with Alkaptonuria is generally good

Additional and Relevant Useful Information for Alkaptonuria:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/

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References and Information Sources used for the Article:


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Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Aug. 4, 2015
Last updated: April 18, 2018