Overview
Alkaptonuria is a rare inherited disorder that affects the way the body processes certain amino acids. It is caused by a deficiency of the enzyme homogentisate 1,2-dioxygenase, leading to a buildup of homogentisic acid in the body. Over time, this buildup can cause darkening of the urine, pigmentation of connective tissues (a condition known as ochronosis), and joint problems. Though it is a lifelong condition, early diagnosis and proper management can help minimize complications.
What is Alkaptonuria?
Alkaptonuria is a genetic metabolic disorder in which the body cannot properly break down the amino acids tyrosine and phenylalanine. This results in the accumulation of homogentisic acid (HGA), which deposits in connective tissues, bones, and cartilage. These deposits lead to discoloration, arthritis, and other systemic complications. The disease is autosomal recessive, meaning a child must inherit two defective copies of the gene (one from each parent) to develop the condition.
Symptoms
- Dark-colored urine (often black when exposed to air)
- Bluish-black discoloration of ear cartilage and eye sclera (ochronosis)
- Early-onset osteoarthritis, especially in the spine and large joints
- Joint stiffness and pain
- Tendon and ligament ruptures
- Heart valve damage (in advanced cases)
- Kidney stones and prostate stones
Symptoms typically start to appear in adulthood, even though urine discoloration can be present in infancy.
Causes
Alkaptonuria is caused by mutations in the HGD gene, which provides instructions for making the homogentisate 1,2-dioxygenase enzyme. This enzyme is necessary for breaking down homogentisic acid. Without it, HGA builds up and deposits in tissues, leading to the disease symptoms.
Risk Factors
- Genetics: Inheriting two copies of the mutated HGD gene (one from each parent)
- Family History: Having parents or close relatives with alkaptonuria
- Ethnic Groups: Slightly more common in specific regions, including parts of Slovakia and the Dominican Republic
Complications
- Severe arthritis requiring joint replacement
- Spinal abnormalities and restricted mobility
- Heart problems, including aortic or mitral valve disease
- Kidney and prostate stones
- Pigmentation changes in skin and eyes
- Chronic pain and decreased quality of life
Prevention
Since alkaptonuria is a genetic disorder, it cannot be prevented. However, genetic counseling can help at-risk families make informed reproductive decisions. Early diagnosis through urine tests or genetic screening can help manage the condition proactively.
Treatment Options in Korea
In South Korea, modern medical facilities provide comprehensive care for rare genetic disorders like alkaptonuria. Treatment is focused on managing symptoms and slowing disease progression. Key options include:
- Medication:
- Nitisinone (NTBC) – helps reduce the production of homogentisic acid. Available under specialist guidance.
- Pain relievers and anti-inflammatory drugs – for arthritis and joint pain.
- Physical Therapy & Rehabilitation:
- Regular physiotherapy to improve mobility and reduce joint stiffness.
- Exercise programs tailored to protect affected joints.
- Orthopedic Interventions:
- Joint replacement surgeries (especially hips and knees) available at leading Korean hospitals such as Severance Hospital, Samsung Medical Center, and Asan Medical Center.
- Cardiac Monitoring:
- Regular heart evaluations using echocardiograms or MRIs for early detection of valve damage.
- Dietary Management:
- Low-protein diets to reduce tyrosine and phenylalanine intake (under dietitian supervision).
- Genetic Counseling:
- Available at specialized centers like the National Health Insurance Service Ilsan Hospital for family planning and understanding genetic risks.
