What is Alkaptonuria?

Alkaptonuria, also known as black urine disease, is a rare genetic disorder that affects the body’s ability to break down certain amino acids, leading to buildup of homogentisic acid (HGA) in the body. This condition results in dark urine, joint problems, and tissue discoloration over time.

Causes of Alkaptonuria

✔ Genetic Mutation in the HGD Gene – The HGD gene provides instructions for producing homogentisate 1,2-dioxygenase, an enzyme responsible for breaking down homogentisic acid (HGA).
✔ Autosomal Recessive Inheritance – A person must inherit two defective copies of the gene (one from each parent) to develop the disorder.
✔ Buildup of Homogentisic Acid (HGA) – When the enzyme is missing or defective, HGA accumulates in the body, leading to dark urine, cartilage damage, and tissue discoloration.

Who is at Risk for Alkaptonuria?

✔ Children of Carrier Parents – If both parents carry a mutated HGD gene, there is a 25% chance of passing the condition to their child.
✔ Both Males and Females are Affected – The disorder is not sex-linked.
✔ Higher Prevalence in Certain Regions – More common in Slovakia and the Dominican Republic due to genetic factors.

Symptoms of Alkaptonuria

Symptoms typically do not appear at birth but develop over time as homogentisic acid builds up in the body.

Early Symptoms (Infancy & Childhood):

✔ Dark Urine – Urine may turn black or dark brown when exposed to air.
✔ No Other Immediate Symptoms – Infants and young children usually appear healthy.

Middle-Age Symptoms (30s-50s):

✔ Joint Pain & Stiffness – Homogentisic acid builds up in cartilage, leading to arthritis, especially in the spine and large joints.
✔ Darkened Ear Cartilage & Sclera (Eye Whites) – Over time, cartilage and connective tissue turn bluish-black (ochronosis).
✔ Tendon & Ligament Stiffness – Reduced flexibility and increased risk of tendon rupture.

Advanced Symptoms (50s & Older):

✔ Severe Arthritis & Joint Degeneration – May require joint replacement surgeries.
✔ Heart Valve Calcification – Increased risk of heart disease and aortic valve narrowing.
✔ Kidney & Prostate Stones – HGA can form stones in the kidneys, bladder, and prostate.

Complications of Alkaptonuria

⚠ Osteoarthritis & Spinal Damage – Chronic HGA buildup weakens joints and spinal discs.
⚠ Heart Problems – HGA deposits can harden heart valves, increasing the risk of heart disease.
⚠ Kidney & Bladder Stones – Painful stones may form in the urinary system.
⚠ Prostate Issues (Men) – HGA buildup can lead to prostate stones and enlargement.

How is Alkaptonuria Diagnosed?

✔ Urine Test – Detects excess homogentisic acid, which turns urine black or dark brown when exposed to air.
✔ Genetic Testing – Identifies mutations in the HGD gene.
✔ Blood & Imaging Tests – Evaluates joint damage, heart valve calcification, and kidney stones.
✔ Physical Examination – Checks for joint stiffness, skin discoloration, and eye changes.

Treatment for Alkaptonuria

There is no cure, but treatment focuses on managing symptoms and slowing disease progression.

Lifestyle & Dietary Management:

✔ Low-Protein Diet (Some Cases) – May help reduce HGA levels.
✔ Vitamin C (Limited Use) – May reduce HGA oxidation, but effectiveness is debated.

Medications:

✔ Nitisinone (NTBC) – Blocks HGA production, slowing the progression of joint damage.
✔ Pain Relievers & Anti-Inflammatory Drugs – Helps manage arthritis pain and stiffness.

Joint & Bone Care:

✔ Physical Therapy – Maintains joint flexibility and mobility.
✔ Joint Replacement Surgery (If Needed) – For severe arthritis in the knees, hips, or spine.

Heart & Kidney Management:

✔ Regular Heart Checkups – Detects and manages heart valve issues early.
✔ Kidney & Prostate Stone Monitoring – Ultrasounds and imaging help prevent complications.

How to Manage Alkaptonuria?

✔ Stay Active – Regular low-impact exercise helps keep joints mobile.
✔ Monitor Urine & Kidney Health – Regular checkups to detect kidney stones early.
✔ Avoid High-Impact Activities – To prevent joint stress and further damage.
✔ Consult a Specialist – A rheumatologist, cardiologist, or geneticist can help tailor treatment.

Prognosis & Life Expectancy

✔ Life Expectancy is Normal – If complications like heart disease and kidney stones are managed.
✔ Quality of Life Depends on Symptom Management – Early intervention reduces arthritis severity and mobility issues.