Alkaptonuria

Alkaptonuria is a rare genetic metabolic disorder characterized by the accumulation of homogentisic acid in the body. Affected individuals lack enough functional levels of an enzyme required to breakdown homogentisic acid. Affected individuals may have dark urine or urine that turns black when exposed to air.

1. ALKAPTONURIA Dr. V. MAGENDIRA MANI., M.Sc., M.Phil., Ph.D., TNSET Assistant Professor of Biochemistry Islamiah College (Autonomous), Vaniyambadi [email protected] ; 9486000227

2. Inborn errors of metabolism (IEMs) are inherited metabolic disorders that result from defects in genes coding for specific enzymes. This defect generates abnormal chemical reactions that disrupt the normal metabolic pathways resulting in the toxic accumulation of the substrate behind the block or a deficiency in the product. Most of the enzymatic alterations in IEMs are inherited as autosomal recessive disorders, the remainder being either autosomal dominant or X-linked. Inborn errors of metabolism

3. Overview Alkaptonuria is a rare inherited disorder. It occurs when mutation /defects enzyme called homogentisic dioxygenase (HGD). This enzyme is used to break down a toxic substance called homogentisic acid. Deficiency of this enzyme leads to homogentisic acid accumulation in your body. also called black urine disease also called black urine disease

4. Alkaptonuria is a rare disease. It is estimated to occur in 1 of every 250,000 –1 million live birth Alkaptonuria is caused by a mutation on your homogentisate 1,2-dioxygenase (HGD) gene. It’s an autosomally recessive condition. This means that both of your parents must have the gene in order to pass the condition on to you. Alkaptonuria

5. Black urine disease or black bone disease is an inborn error of amino acid metabolism. It is a rare inherited genetic disorder of phenylalanine (Phe) and tyrosine (Tyr) metabolism. Autosomal recessive condition (both the parents must have the gene in order to pass to their progeny).

6. Mutations in the HGD gene The gene defect makes the body unable to properly break down certain amino acids (tyrosine and phenylalanine). As a result, a substance called homogentisic acid builds up in the skin and other body tissues. The acid leaves the body through the urine. The urine turns brownish-black when it mixes with air.

7. The buildup of homogentisic acid causes your bones and cartilage to become discolored and brittle. This typically leads to osteoarthritis, especially in your spine and large joints. People with alkaptonuria also have urine that turns dark brown or black when it’s exposed to air. QUICK TIP Try right clicking on a photo and using "Replace Image" to show your own photo.

8. Symptoms of alkaptonuria include: Dark spots in the sclera (white) of your eyes Thickened and darkened cartilage in your ears Blue speckled discoloration of your skin, particularly around sweat Glands Dark-colored sweat or sweat stains Black earwax Kidney stones and prostate stones Arthritis (especially hip and knee joints)

9. a buildup of dark pigment in connective tissues such as cartilage and skin Arthritis (especially of the spine) that gets worse over time Tendinitis is inflammation or irritation of a tendon

10. Darkening of the ear Dark spots on the white of the eye (sclera) and cornea

11. Alkaptonuria can also lead to heart problems. The buildup of homogentisic acid causes your heart valves to harden. The buildup also causes your blood vessels to harden. This raises your risk of high blood pressure. This results in aortic and mitral valve disorders. In severe cases, heart valve replacement may be necessary.

12. A urine test (urinalysis) is done to test for alkaptonuria. If ferric chloride is added to the urine, it will turn the urine a black color in patients with this condition

13. Thank you. Dr. V. MAGENDIRA MANI., M.Sc., M.Phil., Ph.D.,TNSET Assistant Professor of Biochemistry Islamiah College (Autonomous), Vaniyambadi [email protected] ; 9486000227