Which Enzyme Deficiency Causes Alkaptonuria?

Key Facts About Enzyme Deficiency and Alkaptonuria

Alkaptonuria is a rare disease that affects 1 in 100,000 to 1 in 250,000 people. This metabolic disorder interferes with the body's ability to break down amino acids. Alkaptonuria is genetic and progressive. Dark urine and osteoarthritis are the most noticeable signs of this condition. All of this happens because a single enzyme is deficient in the person.

Read ahead to understand which enzyme deficiency causes alkaptonuria, including its symptoms and more details.

Which Enzyme Deficiency is the Reason Behind Alkaptonuria?

Alkaptonuria (black-urine disease) occurs due to a deficiency of an enzyme called homogentisate 1,2-dioxygenase (HGD). This enzyme plays a significant role in breaking down homogentisic acid (HGA). HGA production occurs when the body breaks down amino acids (proteins) such as tyrosine and phenylalanine.

The HGD enzyme plays a significant role in converting homogentisic acid (HGA) into maleylacetoacetic acid. Without HGD, a complete breakdown of HGA (homogentisic acid) is not possible. As a result, HGA accumulates in blood, connective tissues, and urine.

After a long period of accumulation, the HGA oxidizes and starts binding to collagen fibers in connective tissues. This results in arthritis-like symptoms and discoloration of body parts.

What are the Causes of Alkaptonuria?

Alkaptonuria is caused by a mutation in the homogentisate 1,2-dioxygenase (HGD) gene. This gene contains essential information for producing the HGD enzyme. The black-urine disease is an autosomal recessive condition. This means the child inherits two faulty genes, one from each parent. Here are the genetic combinations explained below:

• Two Mutated Genes: The child will have the condition (autosomally recessive)
• One Mutated and One Normal Gene: The child may carry but not have symptoms.
• Two Normal Genes: The child remains unaffected.
  
   

What are the Symptoms of Alkaptonuria?

Symptoms of alkaptonuria show themselves in adulthood. The earliest sign, which we overlook, is when an infant's diaper turns black upon exposure to air. When the person is around 20 to 30 years old, they may start showing symptoms, such as:

• Dark urine (black) when exposed to air.
• Discoloration (dark dots) appears on the white of the eye (sclera)
• Blue-black color on the outer ear covering (on the cartilage)
• Dark coloration of sweat and sweat stains
• Prostate stones (a common symptom in men)
• Stiff joints, especially knees and hips.

A layer of homogentisic acid (HGA) can also develop in the heart valves, causing aortic and mitral valve disorders.

Can the HGD Enzyme Deficiency be Fulfilled?

Currently, there is no cure for alkaptonuria. That means there is no approved drug or enzyme replacement method available. The treatments for this condition focus on preventing and reducing its symptoms. These include:

• Having a low-protein diet
• Intake of vitamin C supplements to slow down tissue discoloration.
• Avoiding manual labor and contact sports.
• Physical therapy for pain management.
• Monitoring regularly for heart and kidney functions.

A trial drug, nitisinone (Orfadin), received approval in the EU in 2020 for this disease. However, it has shown a number of side effects among patients. However, its efficacy and side effects are still under study, and it is not widely approved for alkaptonuria globally.

Alkaptonuria is a rare and lifelong condition. Checking for early signs and diagnosis is the first step in managing this. With ongoing research and clinical trials globally, a manageable way is right around the corner.

Complications associated with alkaptonuria can be costly. Thus, it is essential to have health insurance to secure your health and finances during critical times. At Star Health, we offer coverage for various health conditions under our insurance plans. We also provide hassle-free claim settlement with reduced turnaround time across over 14,000 network hospitals in India.