Introduction of Alkaptonuria

Alkaptonuria is an enzyme deficiency, homogentisic dioxygenase (HGD) rare inherited disorder. It is used to break down a toxic substance called homogentisic acid. Excess to homogentisic acid causes bones and cartilage to become discolored and brittle which causes later osteoarthritis, especially in the spine and large joints. The patient who has alkaptonuria also has urine that turns dark brown or black when it is exposed to air (as shown in the above image).

Symptoms

The following are the common symptoms –

1. Turning of urine to dark brown or black color after exposure to air (within 20-30 seconds)
2. Early-onset osteoarthritis
3. Dark spots in the sclera of the eyes
4. Thickened and darkened cartilage of ears
5. Dark-colored sweat
6. Black earwax
7. Renal stones
8. Prostate stones
9. Arthritis (mainly hip and knee joints)

Laboratory Diagnosis

• Color of urine observation: Changing just after 20-30 seconds of urination
• Homogentisic acid detection: Gas chromatography
• Molecular Testing: Mutation in HGD gene
• Radiological Assay-

1. Spinal X-ray-To find out disk degeneration and calcification in the lumbar spine.
2. Chest X-ray: It is applied to monitor aortic and mitral heart valves.
3. CT scan: To check signs of coronary artery disease.

Treatment

There is no specific treatment so far. Rather, treatment is focused mainly on managing symptoms.

Keynotes

1. Alkaptonuria is due to a mutation on homogentisate 1,2-dioxygenase (HGD) gene.
2. According to the National Institutes of Health (NIH), it is found about 1 in 0.25 million to 1 million people worldwide.
3. It is most common in Slovakia and the Dominican Republic where it is affecting about 1 in 19,000 people.

Further Readings

1. https://rarediseases.org/rare-diseases/alkaptonuria/
2. https://rarediseases.info.nih.gov/diseases/5775/alkaptonura
3. https://emedicine.medscape.com/article/941530-workup
4. https://www.nhs.uk/conditions/alkaptonura/
5. https://ufhealth.org/alkaptonuri