ALKAPTONURIA 123456 1212 121212 .pptx

ALKAPTONURIA

1. ALKAPTONURIA

2. Overview Alka ptonur ia is a rare inherited disorder. It occurs when mutation /defects enzyme called homogentisic dioxygenase (HCD). 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.

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

4. Mutation or defect In HCD gene which causes lack of the enzyme homogentisate diaxygenase (HGD). This causes a build up of homogentisic acid (HGA) in the bones, cantlage and urine. HGA is an intermediate In the degradation pathway of the amino acids (Phe & Tyr ) to the Krebs cycle.

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 g ene defect makes the bod y 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 our 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

8. Symptoms of alkaptonuria include: D ark s pots in the sclera (white) of your eyes Thickened and darkened cartilage in your ears Blue speckled discOlOFation 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 pig'rnent in conñec¥ve tig8ues such as' TenM\nT£fa IB inflarnmaâon Aith'f1tis (e'spddaIly of Iffe spite) thâ\ gels worse over

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

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

12. DIAGNOSIS Urine test - addition of ferric chloride to the urine will change it's color to black. Gas chromatography to look for traces of HGA in urine. DNA testing - to check for mutated HGD gene. It is generally done by analyzing blood sample. Prenatal tests (amniocentesis or chorionic villus sampling) can be done to screen a developing baby for this condition if the genetic change has been identified.

13. TREATMENT The treatment of alkaptonuria is aimed at the specific symptoms. Activities that place significant physical stress to the spine and joints should be avoided. Patients receive anti- inflammatory medications or narcotics to treat joint pain. Physical and occupational therapy- to maintain the strength and flexibility of muscles and joints. Some individuals require surgical intervention.

14. DIETARY RECOMMENDATION High Vitamin C (ascorbic acid) intake is prescribed (1g/day). Best source of vitamin C is fruits and vegetables. Fruits like oranges, indian gooseberry, grapefruit, tangerines , kiwi fruit, strawberries, etc. Vegetables like bFoCcoli, Cabbage, brussels sprouts, tomatoes, green peppers, melons, sweet peppers, potatoes with skin, and alfalfa sprouts. Low diet, especially in the amino acids phe and tyr, can help reduce levels of HGA.

15. Eggs, meat and meat procJucts including pork, lamb, beef, chicken; dairy products like cheese and milk; legumes, nuts, seeds should be restrtcted from the Aspartame (artiRclal sweetener) should be avoided. Sugars, jams, sweets, solid vegetable oils, cooking oils, fruits and vegetables can be given. - Exchanges containing 3g of protein can be given. Phe level should be maintained between 3- 15%. Phe and tyr free chemically defined food can be given. Sufficient energy needs should be met through low protein fbod to assure normal growth.

16. Thank