Alkaptonuria, also called black urine disease is a rare inherited disorder resulting from an autosomal recessive genetic condition. Having two faulty copies of a gene called HGD leads to this condition. Approximately 1 in 250,000 to 1 million people globally suffer from this illness. In early adulthood, people with alkaptonuria start experiencing arthritis, especially in the spine and major joints. Heart issues, kidney stones, and stones in the prostate are also some possible additional symptoms.

Main causes
Alkaptonuria is brought on by homogentisate oxidase (HGD) gene mutation. The HGD gene contains instructions for producing the enzyme homogentisate 1,2-dioxygenase. It is required for the conversion of an intermediate called homogentisic acid, formed in the metabolic pathway of the amino acids phenylalanine and tyrosine. In alkaptonuria, due to the absence of a functional copy of the HGD gene, the enzyme it codes does not get produced, and as a result, the substrate accumulates in the body. The homogentisic acid buildup is mainly in the connective tissues, cartilage, bones, nails, and skin, and it stains all of them black.

Symptoms

• Black urine
  The homogentisic acid excreted through urine oxidizes to benzoquinone acetate polymers when coming in contact with the air. This causes the urine to darken when left standing.
• Ochronosis and black coloration
  Usually beyond the age of 30, ochronosis or bluish-black pigmentation of connective tissue, and black coloration of the ears, eyes, and different body fluids are an indication of this disorder.
• Arthritis and discoloration of the joints
  Large joints and the spine might develop arthritis due to the polymer’s deposition within the cartilage and subchondral bone. This commonly happens in one’s twenties and it typically results in discoloration of the joints. The condition may worsen over time leading to disability.
• Black stones in the kidneys or prostate
  Kidney stones are one of the indications, and they appear in 50% of those who have the condition and are beyond the age of 64. Prostate stones can also occur in men who have alkaptonuria. These black stones do not pass through urine.
• Heart disease
  In some people, heart disease may be brought on by homogentisic acid buildup in the aortic or mitral valves. This accumulation results in the valves becoming thicker and their apertures being stenosed. Sometimes the narrowing is so bad that a new aortic valve needs to be installed.

Diagnostic measures
The condition is diagnosed based on the presence of distinctive symptoms, a thorough review of the patient’s medical history, a careful clinical assessment, and a range of specialized testing. It can be detected by the discovery of significantly high levels of homogentisic acid in the urine. People with black urine should be checked for alkaptonuria. It may be prudent to rule out this disorder for all people with osteoarthritis, especially those with an early onset of symptoms, given that some people with the condition do not have dark urine.

Doctors may suggest checking one’s urine for homogentisic acid by doing a test known as gas chromatography. Additionally, they perform DNA testing to look for the HGD gene mutation. Family history is helpful in the diagnosis. However, many people don’t realize they have the gene and one’s parents might unknowingly be carriers.

Treatment options

• The treatment depends on the unique symptoms that each patient exhibits. Anti-inflammatory options are frequently prescribed to reduce joint pain. Stronger ones may be advised in extreme circumstances. Pain management is individualized for each person’s unique situation and necessitates.
• For some people, surgery is necessary. By the time they are 50 to 60 years old, around half of the people with this disorder may need hip, knee, or shoulder replacement operations. Rarely some patients need spinal surgery, involving the removal or fusion of the lumber discs. Sometimes it becomes essential to have the aortic or mitral valves replaced. Chronic kidney or prostate stones may occasionally need surgical intervention or prophylactic (preventive) treatment.
• Since ascorbic acid reduces the buildup of homogentisic acid in the tissues, high dosages of ascorbic acid (vitamin C) have occasionally been suggested for the treatment. However, studies have indicated that this treatment over a long period is typically ineffective.
• Recently, a wide range of advanced treatments are being developed to stop the creation of homogentisic acid.