Alkaptonuria | Anatomy2Medicine
Alkaptonuria

Alkaptonuria

    • Autosomal-recessive deficiency of homogentisic acid oxidase (degradative pathway of tyrosine),

 

  • benign disease
  • Dark connective tissue, pigmented sclera

 

    • urine turnes black on standing

 

  • may have debilitating arthralgias

 

 

Ochronosis

 

Exam MCQ

Which enzyme defect leads to alkaptonuria:

  1. Tyrosine aminotransferase
  2. Homogentisate oxidase
  3. Maleylacetoacetate isomerase
  4. Fumarylacetoacetate hydroxylase

ANS: B. Tyrosine transaminase enzyme deficiency leads to type II tyrosinemia, results in the accumulation of excretion of tyrosine metabolites (P-hydroxylphenylpyruvate, P-hydroxyphenyllactate, P-hydroxylphenylacetate etc). Alkaptonuria is due to the defect in homogentisate oxidase. Homogentisate levels are increased and accumulate in tissues and blood and excreted into urine, on oxidation in air, which polymerizes to black colour. Homogentisate is also oxidized to pigments that are deposited in bones, connective tissue and other organs (ochronosis). On oxidation in air, this polymerizes to black colour. Type I tyrosinemia is due to the deficiency of the enzymes fumarylacetoacetatehydrolase. Both fumarylacetoacetate and maleylacetate are accumulated and also act as alkylating agents (DNA alkylation), it is a more serious disorder involving in liver failure, renal tubular dysfunction, rickets and poly neuropathy.