Fatal methemoglobinemia complicating alkaptonuria (ochronosis): a rare presentation

Case Report

Abstract

A 61-year-old female died in hospital with multiple organ failure 4 weeks following presentation with acute kidney injury, hemolytic anemia and methemoglobinemia. At autopsy, brown to black discoloration of cartilages was observed. Histology revealed brown pigmentation of the hyaline cartilage, with focal full-thickness erosion of the articular hyaline cartilage, characteristic of alkaptonuria (ochronosis). Although alkaptonuria is rarely fatal, this case illustrates a rare acute fatal complication. Accumulation of circulating homgentisic acid secondary to acute derangement of renal function is believed to have overwhelmed the endogenous antioxidant processes, resulting in hemolysis and methemoglobinemia, which were refractory to treatment. Small numbers of cases have previously been reported in the literature in patients known to suffer with the disease, all of which were preceded by acute kidney injury. Whilst the clinical diagnosis of alkaptonuria may be challenging, the autopsy findings of this rare condition are striking and this case illustrates the utility of the autopsy, albeit retrospectively, in arriving at a diagnosis. To our knowledge this is the first reported case where previously undiagnosed alkaptonuria has presented with methemoglobinemia.

Keywords

Methemoglobinemia Alkaptonuria Ochronosis Autopsy 

Notes

Acknowledgements

We thank Miss Tasma How and the histopathology laboratory at Forensic Science SA for technical support, and Dr. Sui Yu, Mr. Kristian Brion and Mr. Tim Pyragius of SA Pathology for the genetic analysis.

Compliance with ethical standards

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. Approval to report the case was given by Forensic Science SA, Adelaide, Australia.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Abreo K, Abreo F, Zimmerman SW, Hartman H, Gilbert EF, Katcher ML, et al. A fifty-year-old man with skin pigmentation, arthritis, chronic renal failure and methemoglobinemia. Am J Med Genet. 1983;14:97–114.CrossRefPubMedGoogle Scholar
  2. 2.
    Gaines JJ. The pathology of alkaptonuriconchronisis. Hum Pathol. 1989;20:40–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Phornphutkul C, Introne WJ, Perry MB, Bernardini I, Murphey MD, Fitzpatrick DL, et al. Natural history of alkaptonuria. N Engl J Med. 2002;347:2111–21.CrossRefPubMedGoogle Scholar
  4. 4.
    Zatkova A. An update on molecular genetics of alkaptonuria (AKU). J Inherit Metab Dis. 2011;34:1127–36.CrossRefPubMedGoogle Scholar
  5. 5.
    Pollak MR, Chou YH, Cerda JJ, Steinmann B, La Du BN, Seidman JG, et al. Homozygosity mapping of the gene for alkaptonuria to chromosome 3q2. Nat Genet. 1993;5:201–4.CrossRefPubMedGoogle Scholar
  6. 6.
    Braconi D, Millucci L, Bernardini G, Santucci A. Oxidative stress and mechanisms of ochronosis in alkaptonuria. Free Radic Biol Med. 2015;88:70–80.CrossRefPubMedGoogle Scholar
  7. 7.
    Helliwell TR, Gallagher JA, Ranganath L. Alkaptonuria - a review of surgical and autopsy pathology. Histopathology. 2008;53:503–12.PubMedGoogle Scholar
  8. 8.
    Pettit SJ, Fisher M, Gallagher JA, Ranganath LR. Cardiovascular manifestations of alkaptonuria. J Inherit Metab Dis. 2011;34:1177–81.CrossRefPubMedGoogle Scholar
  9. 9.
    Zatkova A. HGD mutation database. http//:hgddatabase.cvtisr.sk. Accessed 1 Nov 2017.
  10. 10.
    Gonzales ME. Alkaptonuric aortic stenosis: a case report. AANA J. 1999;67:145–51.PubMedGoogle Scholar
  11. 11.
    Faria B, Vidinha J, Pego C, Correia H, Sousa T. Impact of chronic kidney disease on the natural history of alkaptonuria. Clin Kidney J. 2012;5:352–5.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Zaraa I, LAbbene I, Trojjet S, Mrabet D, Meddeb N, Chelly, et al. Endogenous ochronosis with a fatal outcome. J Cutan Med Surg. 2012;16:357–60.CrossRefPubMedGoogle Scholar
  13. 13.
    Davison AS, Milan AM, Gallagher JA, Ranganath LR. Acute fatal metabolic complications in alkaptonuria. J Inherit Metab Dis. 2016;39:203–10.CrossRefPubMedGoogle Scholar
  14. 14.
    Heng AE, Courbebaisse MD, Kemeny JL, Matesan R, Bonniol C, Deteix P, et al. Hemolysis in a patient with alkaptonuria and chronic kidney failure. Am J Kidney Dis. 2010;56:e1–4.CrossRefPubMedGoogle Scholar
  15. 15.
    Isa Y, Nihei S, Irifukuhama Y, Ikeda T, Matsumoto H, Nagata K, et al. A rare case of acquired methemoglobinemia associated with alkaptonuria. Intern Med. 2014;53:1797–800.CrossRefPubMedGoogle Scholar
  16. 16.
    Bataille S, Moal V, Aquaron RR, Grünfeld JP, Daniel L. Hemolysis: a fatal complication of alkaptonuria in a severe renal failure patient. Clin Nephrol. 2014;81:374–6.CrossRefPubMedGoogle Scholar
  17. 17.
    Liu W, Prayson RA. Dura mater involvement in ochronosis (Alkaptonuria). Arch Pathol Lab Med. 2001;125:961–3.PubMedGoogle Scholar
  18. 18.
    Uchiyama C, Kondoh H, Shintani H. Acute methemoglobinemia associated with ochronotic valvular heart disease: report of a case. Thorac Cardiovasc Surg. 2010;58:113–9.CrossRefGoogle Scholar
  19. 19.
    Mullan A, Cocker D, Taylor G, Millar C, Ranganath L. Fatal oxidative haemolysis and methaemoglobinaemia in a patient with alkaptonuria and acute kidney injury. Clin Kidney J. 2015;8:109–12.CrossRefPubMedGoogle Scholar
  20. 20.
    Cortazzo JA, Lichtman AD. Methemoglobinemia: a review and recommendations for management. J Cardiothoracic and Vasc Anaesthesia. 2014;28:1043–7.CrossRefGoogle Scholar
  21. 21.
    Chikezi PC, Ekechukwu CU. Acute patho-toxilogical indicators of methaemoglobinaemia. J Acute Dis. 2016;5:179–84.CrossRefGoogle Scholar
  22. 22.
    Varlet V, Ryser E, Ausberger M, Palmiere C. Stability of post-mortem methemoglobin: Artefactual changes caused by storage conditions. Forensic Sci Int. 2018;283:21–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.SA PathologyAdelaideAustralia
  2. 2.Forensic Science SAAdelaideAustralia
  3. 3.The University of AdelaideAdelaideAustralia

Personalised recommendations