Ochronosis as an unusual cause of valvular defect: a case report

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Alkaptonuria (also known as ochronosis) is a genetic disorder characterised by the accumulation of homogentisic acid deposits in connective tissue. In rare cases, ochronosis can cause valvular heart disease.

Case presentation
We present the case of a 68-year-old Caucasian man with alkaptonuria-associated degenerative valvular defects with aortic, mitral and tricuspid valve insufficiency. The patient did not have any cardiac complaints and was referred to our clinic for evaluation of a conspicuous new heart murmur.

This case report shows that early diagnosis of cardiovascular ochronosis gives us the opportunity to use conservative treatment to slow down the progression of valvular dysfunction.


Alkaptonuria is a rare autosomal-recessive metabolic disorder characterised by the deficiency of homogentisic 1,2-dioxygenase (HGO) [1]. Due to the lack of this enzyme, homogentisic acid cannot be metabolised and is deposited within various tissues of the body as a polymerised product. The common clinical manifestations of alkaptonuria are (i) homogentisic aciduria, (ii) ochronosis (deposition of bluish-black pigment in all connective tissues), and (iii) arthritis. While alkaptonuria itself is asymptomatic, ochronosis usually develops in the fourth decade of life. There is no cure for alkaptonuric ochronosis and the aim of treatment is to prevent complications.


  1. Van Offel JF, De Clerck LS, Francx LM, Stevens WJ: The clinical manifestations of ochronosis: a review. Acta Clin Belg 1995, 50:358-362.
  2. Zatkov─é╦ç A, de Bernab─é┬® DB, Pol─é╦çkov─é╦ç H, Zvar─é┬¡k M, Fer─é╦çkov─é╦ç E, Bos─é╦çk V, Fer─é╦çk V, K─é╦çdasi L, de C─é┼érdoba SR: High frequency of alkaptonuria in Slovakia: evidence for the appearance of multiple mutations in HGO involving different mutational hot spots. Am J Hum Genet 2000, 67:1333-1339.
  3. Lee SL, Stenn FF: Characterization of mummy bone ochronotic pigment. JAMA 1978, 240:136-138.
  4. Virchow R: Ein Fall von allgemeiner Ochronose der Knorpel und knorpelähnlichen Theile. Virchows Arch 1866, 37:212-219.
  5. Janocha S, Wolz W, Srsen S, Srsnova K, Montagutelli X, Gu─é┬®net JL, Grimm T, Kress W, M─é─¢ller CR: The human gene for alkaptonuria (AKU) maps to chromosome 3q. Genomics 1994, 19:5-8.
  6. Phornphutkul C, Introne WJ, Perry MB, Bernardini I, Murphey MD, Fitzpatrick DL, Anderson PD, Huizing M, Anikster Y, Gerber LH, Gahl WA: Natural history of alkaptonuria. N Engl J Med 2002, 347:2111-2121.
  7. Zannoni VG, Lomtevas N, Goldfinger S: Oxidation of homogentisic acid to ochronotic pigment in connective tissue. Biochim Biophys Acta 1969, 177:94-105.
  8. Touart DM, Sau P: Cutaneous deposition diseases. Part II. J Am Acad Dermatol 1998, 39:527-544.
  9. Gupta A, Jayanti A, Prasanna K: Premature arthritis in an elderly woman. Int J Clin Pract 2006, 60:858-860.
  10. Gaines JJ Jr: The pathology of alkaptonuric ochronosis. Hum Pathol 1989, 20:40-46.
  11. Gaines JJ Jr, Pai GM: Cardiovascular ochronosis. Arch Pathol Lab Med 1987, 111:991-994.
  12. Kim YI, Daenen W: Aortic valve replacement in cardiac ochronosis. Eur J Cardiothorac Surg 1992, 6:625-626.
  13. Erek E, Casselman FR, Vanermen H: Cardiac ochronosis: valvular heart disease with dark green discoloration of the leaflets. Tex Heart Inst J 2004, 31:445-447.
  14. Hangaishi M, Taguchi J, Ikari Y, Ohno M, Kurokawa K, Kotsuka Y, Furuse A: Aortic valve stenosis in alkaptonuria. Images in cardiovascular medicine. Circulation 1998, 98:1148-1149.
  15. Butany JW, Naseemuddin A, Moshkowitz Y, Nair V: Ochronosis and aortic valve stenosis. J Card Surg 2006, 21:182-184.
  16. Roser M, M─é┬Âller J, Komoda T, Knosalla C, Stawowy P: Alkaptonuric aortic stenosis. Eur Heart J 2008, 29:444.
  17. Mayatepek E, Kallas K, Anninos A, M─é─¢ller E: Effects of ascorbic acid and low-protein diet in alkaptonuria. Eur J Pediatr 1998, 157:867-868.
  18. Fisher AA, Davis MW: Alkaptonuria ochronosis with aortic valve and joint replacements and femoral fracture: a case report and literature review. Clin Med Res 2004, 2:209-215.
  19. Suwannarat P, O'Brien K, Perry MB, Sebring N, Bernardini I, Kaiser- Kupfer MI, Rubin BI, Tsilou E, Gerber LH, Gahl WA: Use of nitisinone in patients with alkaptonuria. Metabolism 2005, 54:719-728.