What Is Alkaptonuria?

Highlights
1. Alkaptonuria is a rare genetic disorder that causes homogentisic acid to
build up in your body.
2. A build-up of homogentisic acid causes your urine to turn dark blue or
black when exposed to air. It also causes your bones and cartilage to
become discolored and brittle.
3. Treatment for alkaptonuria focuses on preventing and relieving possible
complications, such as osteoarthritis and coronary heart disease.

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.

SYMPTOMS

What Are the Symptoms of Alkaptonuria?

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.

AD V ER T IS E M E N T

CAUSES

What Causes Alkaptonuria?

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 Organization of Rare

Disorders (NORD), the exact number of cases is unknown. It is estimated to
occur in 1 of every 250,000 –1 million live births in the United States. However,
it’s more common in certain areas of Slovakia, Germany, and the Dominican
Republic.

DIAGNOSIS

How Is Alkaptonuria Diagnosed?

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.

AD V ER T IS E M E N T

TREATMENT

How Is Alkaptonuria Treated?

There’s no specific treatment for alkaptonuria.

You may be put on a low-protein diet. Your doctor may also recommend large
doses of ascorbic acid, or vitamin C, to slow down the accumulation of
homogentisic acid in your cartilage. However, NORD warns that long-term use
of vitamin C has generally proven ineffective for treating this condition.

Other treatments for alkaptonuria are focused on preventing and relieving

possible complications, such as:

 arthritis
 heart disease
 kidney stones
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. For

example, NORD reports that approximately half of people with alkaptonuria
need a shoulder, knee, or hip replacement, often by age 50 or 60. 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.

Researchers are currently studying the use of the drug nitisinone as a possible
treatment for alkaptonuria.

OUTLOOK

What Is the Outlook for Alkaptonuria?

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:

 spinal X-rays to check for disk degeneration and calcification in your

lumbar spine
 chest X-rays to monitor your aortic and mitral heart valves
 CT (computed tomography) scans to find signs of coronary artery disease