Alkaptonuria

What is alkapatonuria?

Alkaptonuria is known for its genetic origin. In essence, it is an inherited disease.

It develops when the body can no longer produce sufficient amount of the enzyme, homogentisic dioxygenase (HGD). Homogentisic dioxygenase is responsible for the breaking down of homogentisic acid.

Homogensitic acid is a toxic acid. A lack of homogentisic dioxygenase will therefore cause homogensitic acid to accumulate in the body. Large amounts of this toxic acid will basically affect the bones and large joints. It causes them to become brittle and discolored. Osteoarthritis, particularly in the spinal cord, can be developed thus.

Homogentisic acid will also make the urine to be black and sometimes, brown upon exposure to air.

What are the symptoms of alkaptonuria?

A baby whose diapers are typically dark-stained might be suffering from alkaptonuria. In fact, that is one of the early signs of the disorder. As the baby grows, more symptoms begin to ‘emerge’. Urine, when exposed to the air, will change to either black or dark brown.

When the child begins to approach 20 or 30, osteoarthritis might begin to set in. Chronic stiffness, pain in the large joints and lower back accompanies osteoarthritis.

 Other symptoms of alkaptonuria are:

  • dark spots in the white of the eyes
  • thick and dark ear cartilage
  • blue spotted skin discoloration around the sweat glands
  • dark-colored sweat
  • black earwax
  • kidney stones
  • prostate stones
  • arthritis in the joint of the hip and knee

Alkaptonuria can also affect the heart. Homogentisic acid deposits in the heart can harden its valves and make them not to close properly. This will often result in disorders of the aortic and mitral valves that can make their replacement non-negotiable. Blood vessels will not be left out from the effects of homogentisic acid build up. They will become hardened and make it really hard for blood to readily flow through them. This can raise the risk of developing high blood pressure.

Alkaptonuria
Photo Credit: NHS

What causes alkaptonuria?

Alkaptonuria is a result of a mutation in the gene, homogentisate 1, 2-dioxygenase (HGD). For a child to inherit the disease, both parents must have this defective gene. Hence, it is referred to as an autosomally recessive disease.

The National Organization of Rare Disorders (NORD) submits that there are no exact statistics for alkaptonuria. It is that rare. But there are estimates that put its occurrence at 1 in every 250,000 –1 million live births in the US.

However, it seems more occurrence of alkaptonuria is seen in Germany, Slovakia and the Dominican Republic.

How is alkaptonuria diagnosed?

Dark-colored urine upon exposure to the air is likely going to be the very first sign the doctor will use to suspect that someone has alkaptonuria. This is followed by osteoarthritis.

Traces of homogentisic acid in urine can also be used to diagnose alkaptonuria. A gas chromatography will be employed to do this.

A DNA test can also be ordered for to check for the presence of the bad HGD gene.

The doctor will also find out if alkaptonuria runs in the family since it can be carried by any of the parent and even grandparents.

How is alkaptonuria treated?

Alkaptonuria has no specific treatment.

Low-protein diet and large doses of vitamin C can reduce the accumulation of homogentisic acid in the cartilage. However, NORD has warned that using vitamin C for a very long time can be ineffective in the treatment of alkaptonuraia.

Other treatments are targeted towards relieving symptoms and preventing likely complications such as:

Anti-inflammatory medications are used to relieve joint pain. Physical and occupational therapy can be employed to make the joints and muscles flexible and gain strength. Strenuous activities that greatly impact the joints (i.e. contact sports, heavy manual etc.) should be avoided as much as possible.

The shoulder, knee, aorta, mitral valve or hip might have to be replaced much later in life depending on the severity of the condition. At least, about 50% of alkaptonuria patients will undergo any of these surgical operations in their lifetime.

Stones in the kidney or prostate will also have to be removed surgically.

Nitisinone is a drug that is currently been understudied. It has the potential of treating alkaptonuria.

What is the outlook for alkaptonuria?

People with alkaptonuria have a fair life expectancy. However, the disease comes with other risks:

  • arthritis in the knees, spine, shoulders, and hips
  • tearing of the Achilles tendon
  • hardening of  the heart valves – aortic and mitral valves
  • hardening of the coronary arteries
  • kidney stones
  • prostate stones

These complications can be slowed with regular checkups. Regular checkups will be great in the long run.

The following tests can be used to monitor the progress alkaptonuria:

  • spinal X-rays – to assess lumbar spine calcification and disk degeneration
  • chest X-rays – to assess the integrity of the mitral and aortic valves.
  • Computed tomography (CT) scans – to assess coronary artery disease

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