Alkaptonuria
Alkaptonuria or black urine disease is a rare disease that occurs due to a genetic mutation of homogentisate 1,2-dioxygenase (HGD). The HGD gene mutation that occurs causes the homogentisate oxidase enzyme to fail to work properly. This enzyme functions to break down and decompose two amino acids called tyrosine and phenylalanine.
People with this disease experience a buildup of a chemical called homogentisic acid in the body, causing urine and certain body parts to turn dark. This disease can occur since childhood but can go undetected until adulthood because it sometimes does not cause symptoms.
This disease is quite rare because it only occurs in one in every 250,000 people in the world. There are certain countries that have more cases of this disease than other countries. However, you need to know that this disease can occur in men and women of all ages.
Symptoms of Alkaptonuria
The typical early symptom of too much HGA in the body is dark to black urine, which usually occurs from birth. Beyond that, symptoms of this condition can occur in almost any part of the body, from tendons, bones, nails, ears, and liver.
1. Ochronosis and ochronotic osteoarthropathy
Sufferers can experience ochronosis and ochronotic osteoarthropathy in adulthood with symptoms that are slow. Ochronosis is a bluish-black patch/color due to the accumulation of HGA in certain parts of the body, such as connective tissue.
These symptoms usually begin to appear in the 3rd–5th decade and are found in the eyes and ears, and can also be present on the skin. In addition to the occurrence of a bluish-black color in the ears, thickening can also occur, such as in the ear cartilage.
2. Joint problems
Symptoms such as pain or stiffness in the joints can also occur. Initially, the pain will be felt in the lower back, then spread to the knees, waist, and shoulders. These symptoms are similar to those of osteoarthritis.
In severe cases, the sufferer’s cartilage can also potentially weaken and become damaged. This can lead to joint damage and the need for joint replacement surgery.
3. Accumulation of homogentisic acid
This can happen to connective tissues such as ligaments, bones (arthropathy), and tendons. These tissues will become blackish, weak, and easily damaged. This can cause thickening of the tendons or inflammation (tendonitis) in sufferers.
4. Organ problems
Sufferers can also experience aortic valve stenosis in the heart, kidney stones, and prostate stones. This can occur due to homogentisic acid deposits in the organs so that the organs and blood vessels harden.
5. Discoloration of eyes, skin, and nails
This disease can also cause black and brown spots to appear on the whites of the eyes. In addition, the skin and nails can also change color to have bluish or blackish spots. Skin color can change throughout the body. These changes are most visible in areas that have sweat glands such as the cheeks, forehead, and armpits.
Risk Factors for Alkaptonuria
Alkaptonuria is a hereditary disease. This disorder is inherited in an autosomal recessive manner, meaning it can be inherited when both parents have the same abnormal gene but do not have symptoms. However, if one parent is normal and the other has alkaptonuria, the child is at risk of developing alkaptonuria but without symptoms.
This disease can be experienced by anyone, both men and women. However, in men, this condition is more likely to develop with quite severe symptoms.
Causes of Alkaptonuria
The cause of alkaptonuria is a mutation in the homogentisate 1,2-dioxygenase (HGD) gene. This gene functions to control the production of the homogentisate oxidase enzyme which functions to break down the amino acids tyrosine and phenylalanine in the body.
In the case of alkaptonuria sufferers, this gene is malfunctioning, which causes the sufferer’s body to not have enough enzymes to break down both amino acids. As a result, homogentisic acid (HGA) accumulates in the sufferer’s body.
Under normal conditions, if there is excess homogentisic acid it will be excreted from the body by the kidneys. However, alkaptonuria disease causes homogentisic acid to not be excreted completely, so it accumulates in various body tissues and causes symptoms of alkaptonuria.
Diagnosis of Alkaptonuria
Alkaptonuria can usually be diagnosed based on its typical symptoms, family history, and homogentisic acid level testing. In cases of family history, the disease occurs hereditarily from the parents’ genes.
A person must inherit two abnormal HGD genes, one from their mother and one from their father, to develop the disease. This is so rare that the condition is considered rare.
In some cases, people with alkaptonuria have bone or joint inflammation at a young age, but do not have complaints of dark urine. Homogentisic acid examination can be checked through urine examination with gas chromatography-mass spectrometry analysis.
Another way can be done using X-ray and CT scan methods (imaging methods). This is done to determine the presence of joint, spinal, and heart valve disorders. Finally, by detecting HGD gene mutations with molecular examination.
Treatment of Alkaptonuria
Until now there is no treatment or therapy that can cure alkaptonuria. Because this disease occurs throughout life, the treatment is done to reduce symptoms and reduce the risk of worsening of the disease.
Here are some ways to treat the disease that your doctor might recommend.
1. Nitisinone
This drug can reduce the level of homogentisic acid in the body. Nitisinone can slow the rate of disease progression and its consumption needs to be with a doctor’s recommendation. Nitisinone can be consumed by sufferers together with pain relievers.
2. Physiotherapy
Doing physiotherapy can also be an option for people with alkaptonuria. If stable and routine, physiotherapy can build muscles and strengthen joints. Physiotherapy can also reduce the symptoms that sufferers experience.
It is best to avoid strenuous activities while you are undergoing physiotherapy. You can also find out more about whether exercises such as Pilates Can Prevent Alkaptonuria.
3. Meet certain nutritional needs
People with this disease should also consume foods low in tyrosine and phenylalanine protein, as well as consume ascorbic acid (vitamin C). A low-protein diet can also reduce the side effects of taking nitisinone.
Complications of Alkaptonuria
There are several complications that can occur due to this disease. Usually, the complications that occur are due to the severity of the disease and how long the sufferer has had this disease.
The complications that can occur are:
- Arthritis.
- Heart disease.
- Kidney disorders.
Prevention of Alkaptonuria
Alkaptonuria can be prevented by gene testing for every couple who are going to get married as an early detection. Especially, if one of the partners has a family history of this disease.
When to See a Doctor?
If you or your family have indications of symptoms or signs that point to alkaptonuria, immediately discuss it with a doctor to get the right treatment.