Review Question - QID 106623

This patient is presenting with arthritis due to alkaptonuria (also known as Ochronosis or Ochronotic arthritis) which is due to the deficiency in homogentisate oxidase.

Alkaptonuria is due to the inability to breakdown homogentisic acid, the breakdown products of tyrosine and phenylalanine metabolism, resulting from a deficiency of homogentisate oxidase. Patients typically have the onset of symptoms before the 3rd decade of life due to the accumulation of homogentisic acid. They will present with arthritis due to accumulation within the cartilage, resulting in a black discoloration of the cartilage. Similarly, the skin and sclera discolor, and the urine discolors upon sitting in open air due to the oxidizing oxygen or upon addition of an oxidizing agent to the urine.

Ranganath et al. review advances in the treatment of alkaptonuria. Although many therapies have been tried such as ascorbic acid and a low protein diet, the only true therapy is the early detection and treatment of the complication of alkaptonuria. Palliative care, arthroplasty, and spinal surgery are important to alleviate the effects of the disease. A potential disease-modifying drug, nitisonone, inhibits 4-hydroxy-phenyl-pyruvate-dioxygenase. This inhibits the formation of homogentisic acid and may someday be used to treat these patients.

Introne and Gahl review alkaptonuria as caused by the deficiency of homogentisate oxidase responsible for the conversion of homogentisic acid to maleylacetoacetic acid. The discoloration seen in the urine is due to the oxidation of homogentisic acid resulting in a melanin-like product that produces the dark discoloration.

Figure A shows the discoloration of the cartilage due to the deposition of homogentisic acid. Illustration A and B show the discoloration of the skin and sclera in alkaptonuria, respectively. Illustration C depicts the discoloration of the urine when an oxidizing agent is added to it (Note: the urine will turn black if left in open air as oxygen is an oxidizing agent).

Incorrect Answers:
Answer 1: Phenylalanine hydroxylase is deficient in phenylketonuria.
Answer 2: Branched-chain ketoacid dehydrogenase is deficient in maple syrup disease.
Answer 4: Cystathionine synthase is deficient in homocystinuria.
Answer 5: Methylmalonyl-CoA mutase is deficient in methylmalonic aciduria.