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Alkaptonuria is a genetic disorder, which is characterized by the accumulation of homogentisic acid. Patients with alkaptonuria fail to metabolize tyrosine and phenylalanine. One of the characteristic symptoms of alkaptonuria is the dark colored urine when it is exposed to air. Alkaptonuria in patients occurs as a result of mutation in a gene that codes for homogentisate 1,2-dioxygenase.

Alkaptonuria is a rare genetic disorder; however, in regions of Slovakia and Dominican Republic, the disease is more common, and occurs as a result of multiple mutations as opposed to single mutations in the homogentisate 1,2-dioxygenase gene. The prevalence of alkaptonuria is rare, and affects one individual in up to one million people.

Alkaptonuria is genetic disorder that results from the mutation in homogentisate 1,2-dioxygenase gene. This gene is responsible for coding the enzyme, which is involved in the metabolism of homogentisic acid. As a result of this mutation, homogentisic acid, produced by liver, eventually gets accumulated in the body. As a result, upon urination, the excess acid is passed from the body. Presence of the acid in the urine causes it to turn black when left standing.

The condition is genetic in nature and is passed from parents to offspring. If both the parent are carriers, the child has 25 percent chances of developing the disease.

Symptoms Of Alkaptonuria
Alkaptonuria affects both adults and children with almost similar prevalence. However, in children, the symptoms are less pronounced as compared to adults.

  • Dark stains on baby diapers
  • Brown or black urine
  • Pigmentation in eye or cartilage

In adults, the symptoms are more apparent. Some of the common symptoms are:

  • Development of arthritis or knee disorder
  • Kidney stones
  • Skin pigmentation, especially around sweat glands
  • Dark colored cartilage in ear, nose, or other exposed surfaces
  • Low back pain
  • Osteoporotic bones
  • Irregular heart rhythms
  • Sialolithiasis

Alkaptonuria is asymptomatic in children and young adults, therefore, can be evaluated based on simple urine testing. However, in adults, the disorder is diagnosed as follows:

DNA testing
Used to detect the presence of any mutation in the homogentisate 1,2-dioxygenase gene. Moreover, this test also highlights the point mutations associated with the gene (in more prevalent regions).

This procedure is used to detect the presence of homogentisic acid in the urine sample. The test is inexpensive and efficient in the detection.

Besides, family history, presence of stains on clothes, etc. are some of the common diagnostic strategies used in alkaptonuria.

Treatment Strategies In Alkaptonuria
No specified treatment strategy is demonstrated to treat alkaptonuria. However, various methods or use of products are employed that help in the management of ochronosis associated with the genetic disorder.

Vitamins C
Vitamin C or ascorbic acid has been found to be satisfactory in preventing the accumulation of homogentisic acid in ear cartilage.

Low Phenylalanine Intake
Foods rich in phenylalanine are restricted in patients with alkaptonuria. These include: soy or soy products, nuts, animal protein, milk and milk products, artificial sweeteners, candies, and plant seeds. Restricting phenylalanine reduces the level of homogentisic acid accumulation or ochronosis.

Nitrisinone is found to be an effective inhibitor of 4-hydroxyphenylpyruvate dioxygenase that converts tyrosine to homogentisic acid.

Some of the common complications associated are:

1. Arthritis
In most of the patients, arthritis is commonly observed. Ochronosis is primarily responsible for the development of arthritis in elderly people and various other bone-related disorders. Another common complication is osteoarthritis.

2. Heart Disease
Excess accumulation of homogentisic acid affects the valves in the heart, which eventually leads to coronary heart disease or heart failure in severe cases.

3. Respiratory Disease
Ochronosis has been found to be associated with the development of respiratory disorders, particularly difficulty in breathing and infection of the trachea and larynx.

Although the disorder is genetic in nature, various tests and patient education strategies have been found to be effective in its prevention.

Prenatal Tests
These include chorionic villus sampling or amniocentesis. These tests detect any genetic alteration in the fetus.

It is typically used to educate people with family history of alkaptonuria.

Alkaptonuria is a rare genetic disorder, which results due to the mutation in  homogentisate 1,2-dioxygenase gene. One of the most characteristic symptoms associated with the disorder is the dark coloration of urine when left standing. Treatment strategies include vitamin C, nitisinone, and reduced intake of phenylalanine-rich diet.


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