Alkaptonuria is a rare inherited disorder. It occurs when your body can’t produce enough of an enzyme called homogentisic dioxygenase (HGD). This enzyme is used to break down a toxic substance called homogentisic acid.
When you don’t produce enough HGD, homogentisic acid builds up in your body. The buildup of homogentisic acid causes your bones and cartilage to become discolored and brittle.
This typically leads to osteoarthritis, especially in your spine and large joints. People with alkaptonuria also have urine that turns dark brown or black when it’s exposed to air.
Dark stains on a baby’s diaper are one of the earliest signs of alkaptonuria. There are few other symptoms during childhood. Symptoms become more obvious as you age.
Your urine may turn dark brown or black when it’s exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis.
For example, you may notice chronic stiffness or pain in your lower back or large joints.
Other symptoms of alkaptonuria include:
- dark spots in the sclera (white) of your eyes
- thickened and darkened cartilage in your ears
- blue speckled discoloration of your skin, particularly around sweat glands
- dark-colored sweat or sweat stains
- black earwax
- kidney stones and prostate stones
- arthritis (especially hip and knee joints)
Alkaptonuria can also lead to heart problems. The buildup of homogentisic acid causes your heart valves to harden. This can keep them from closing properly, resulting in aortic and mitral valve disorders.
In severe cases, heart valve replacement may be necessary. The buildup also causes your blood vessels to harden. This raises your risk of high blood pressure.
Alkaptonuria is caused by a mutation on your homogentisate 1,2-dioxygenase (HGD) gene. It’s an autosomally recessive condition.
This means that both of your parents must have the gene in order to pass the condition on to you.
Alkaptonuria is a rare disease. According to the National Institutes of Health, the condition affects about 1 in 250,000 to 1 million people worldwide, but is more common in Slovakia and the Dominican Republic, affecting about 1 in 19,000 people.
Your doctor may suspect you have alkaptonuria if your urine turns dark brown or black when it’s exposed to air. They may also test you for the condition if you develop early onset osteoarthritis.
Your doctor can use a test called gas chromatography to look for traces of homogentisic acid in your urine. They can also use DNA testing to check for the mutated HGD gene.
Family history is very useful in making a diagnosis of alkaptonuria. However, many people don’t know they carry the gene. Your parents might be carriers without realizing it.
There’s no specific treatment for alkaptonuria. Instead, treatment is focused largely on managing symptoms.
There are many therapies that have been tried, but unfortunately they haven’t been proven to be effective, and may be harmful or unhelpful in the long term.
Other treatments for alkaptonuria are focused on preventing and relieving possible complications, such as:
For example, your doctor may prescribe anti-inflammatory medications or narcotics for joint pain. Physical and occupational therapy may help you maintain flexibility and strength in your muscles and joints.
You should also avoid activities that put a lot of strain on your joints, such as heavy manual labor and contact sports. At some point in your life, you might need surgery.
You may also require surgery to replace your aortic or mitral heart valves, if they stop working properly. In some cases, you may need surgery or other therapies to treat chronic kidney or prostate stones.
The life expectancy for people with alkaptonuria is fairly normal. However, the disease puts you at much higher risk of certain disorders, including:
- arthritis in your spine, hips, shoulders, and knees
- tearing of your Achilles tendon
- hardening of your heart’s aortic and mitral valves
- hardening of your coronary arteries
- kidney and prostate stones
Some of these complications can be delayed with regular checkups. Your doctor will want to monitor you regularly. Tests to monitor the progress of your condition might include: