4. • In 1908, Garrod coined the
term ′inborn error of
metabolism′ and
• proposed that alkaptonuria
resulted from the deficiency of
an enzyme that normally splits
the aromatic ring of
homogentisic acid.
• Chromosome 3q
8. Deficiency of the enzyme homogentisic acid oxidase
Increased levels of homogentisic acid (an intermediate metabolite of
phenylalanine and tyrosine metabolism)
resulting in
9. Homogentisic acid--- OXIDIZED Benzoquinone acetate- polymerised to
alkaptone bodies
Deposition of alkaptone bodies lead to a bluish-black discoloration of the
cartilage as well as degeneration, inflammation, and calcification of the
tendons, ligaments, intervertebral discs, and large joints and increased bone
resorption.
10. A brittle and fragmented cartilage forms and leads to aberrant loading of the
subchondral bone..
These fragments then adhere to the synovial membrane and cause fibrosis
or chondromatosis, leading to ochronotic arthropathy
11. • Patients are typically asymptomatic in childhood.
• However, during the second to third decade of
life, ochronosis may begin to manifest as a blue
or brown pigmentation within the ear cartilage or
the sclera; stones (renal, prostatic, gall bladder,
and salivary glands); back or peripheral joint pain;
rupture of the tendons, muscles, or ligaments;
renal failure; osteoporosis; or fractures
12. • Ochronotic tendinopathy most commonly
affects the patellar or Achilles tendon and can
lead to enthesopathy or spontaneous tendon
ruptures.
13. Clinical picture
• Onset occurs in infancy & childhood
• Urine blackens on standing & diapers become
stained
• Blackish spots in eyes, dorsum of hand, pinna+
• Brown macules on the sclera (Osler's sign).
• No intellectual deficits
14. • Ochronotic pigments deposited in the bone
impair the bone mineralization process and
lead to osteopenia or osteoporosis.
19. Lab Diagnosis
• Diagnostic reaction – Bluish green coloration
produced by addition of dilute ferric chloride
solution to urine – FERRIC CHLORIDE TEST +VE
• Benedicts test +ve
• Urine becomes dark on standing when it
becomes alkaline. Blackening is accelerated on
exposure to sunlight & O2. Urine wen kept in a
test tube will start to blacken from top layer
• Silver Nitrate test +ve
20. Rx
• Nitisonine ( reversible inhibitor 4- hydroxyl
phenyl pruvate oxidase, an enzyme in tyrosine
catabolic pathway)- 2mg once daily
• Reduce intake of food containing tyrosine &
phenylalanine + administration of Vitamin C
