what is Alkaptonuria: Causes, Symptoms and Diagnosis

What Is Alkaptonuria? 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. 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. 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 Email this page Your privacy is important to us How helpful was it? How can we improve it? Medically reviewed by Steve Kim, MD on February 25, 2016 — Written by Janet Barwell and Elizabeth Boskey, PhD