Exacerbation of the ochronosis of alkaptonuria due to renal insufficiency and improvement after renal transplantation.

Abstract

In alkaptonuria, homogentisate 1,2-dioxygenase deficiency causes tissue accumulation of homogentisic acid (HGA), followed by signs and symptoms of ochronosis. These include massive urinary excretion of HGA, arthritis and joint destruction, pigmentation of cartilage and connective tissue, and cardiac valve deterioration. We describe a 46-year-old man with alkaptonuria and diabetic renal failure whose plasma HGA concentration was twice that of any other alkaptonuria patient, and whose ochronosis progressed much more rapidly than that of his two alkaptonuric siblings. After renal transplantation, the plasma HGA normalized, and the daily urinary excretion of HGA decreased by 2-3g. This case illustrates the critical role of renal tubular secretion in eliminating HGA from the body, and suggests that renal transplantation in a uremic patient not only restores HGA excretion, but may also provide homogentisate 1,2-dioxygenase activity for the metabolism of HGA.

• Authors: Wendy J Introne, Chanika Phornphutkul, Isa Bernardini, Kevin McLaughlin, Diana Fitzpatrick, William A Gahl
• Journal: Molecular genetics and metabolism (Mol Genet Metab) 2002 Sep-Oct Vol. 77 Issue 1-2 Pg. 136-42 ISSN: 1096-7192 [Print] United States
• PMID: 12359141 (Publication Type: Case Reports, Journal Article)

Chemical References

• DNA
• Oxygenases
• Dioxygenases
• Homogentisate 1,2-Dioxygenase
• Homogentisic Acid

Topics

• Adult
• Alkaptonuria (complications, enzymology, genetics, surgery)
• Base Sequence
• DNA (genetics)
• DNA Mutational Analysis
• Diabetic Nephropathies (complications, surgery)
• Dioxygenases
• Female
• Homogentisate 1,2-Dioxygenase
• Homogentisic Acid (metabolism)
• Humans
• Kidney Failure, Chronic (complications, surgery)
• Kidney Transplantation (physiology)
• Male
• Middle Aged
• Mutation
• Ochronosis (etiology, pathology)
• Oxygenases (deficiency, genetics)
• Radiography
• Spine (diagnostic imaging)