General knowledge about the disease with dietary recommendations.

1. ALKAPTONURIA
By-
Saniya Khan
M.Sc. DAN (1st Sem)

2. INTRODUCTION
• 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).

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

5. SYMPTOMS
• Urine becomes black when exposed to air.
• Osteoarthritis (mainly spine, hips, shoulders and
knees).
• Black spots in the sclera of the eye (Ochronosis).
• Discolored ear and dark earwax.
• Heart valves are affected by the accumulation of HGA.
• Blue-black speckled discoloration of the skin.
• Kidney, prostate and bladder stones due to the build-
up of HGA in the genito-urinary tract, during urine
production.

7. 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.

8. 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.

9. • In older children and adults, high-doses of vitamin C
is recommended because it hinders the
accumulation and deposition of HGA and may slow
down the progression of arthritis.
• Nitisinone (experimental drug ), an inhibitor of the
enzyme 4-hydroxyphenylpyruvate dioxygenase,
which mediates formation of HGA, has been
reported.

10. 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 broccoli, cabbage, brussels sprouts,
tomatoes, green peppers, melons, sweet peppers,
potatoes with skin, and alfalfa sprouts.
• Low protein diet, especially in the amino acids phe and
tyr, can help reduce levels of HGA.

11. • Eggs, meat and meat products including pork, lamb,
beef, chicken; dairy products like cheese and milk;
legumes, nuts, seeds should be restricted from the
diet.
• Aspartame (artificial sweetener) should be avoided.
• Sugars, jams, sweets, solid vegetable oils, cooking oils,
fruits and vegetables can be given.
• Exchanges containing 1g 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 food to assure normal growth.