Abstract
Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis due to a mutation in the porphobilinogen deaminase gene. The mutation causes a deficiency in the porphobilinogen deaminase enzyme, thereby causing an accumulation of heme precursors (δ-aminolevulinic acid and porphobilinogen). These neurotoxic heme precursors elicit acute neurovisceral attacks, which can be treated with heme-arginate infusions. Some patients require heme-arginate infusions on a regular basis for many years, which ultimately leads to an iron accumulation (increased serum ferritin and iron accumulation in the liver, spleen, and bone marrow on MRI). We report three AIP patients, who developed iron accumulation (with serum ferritin up to 7,850 microgram/liter) due to multiple heme-arginate infusions. We report for the first time that the iron accumulation in these patients was associated with fibrosis on liver histology.
Conclusion: Regular heme-arginate treatment in AIP does not only lead to increased serum ferritin but may also induce liver fibrosis. This should be taken into account, when weighing the risks and benefits of repeated heme-arginate treatment against the risk and benefits of treating refractory AIP by liver transplantation.
Competing interests: None declared
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References
Anderson KE, Bloomer JR, Bonkovsky HL et al (2005) Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 14:439–450
Badminton MN, Elder GH (2002) Management of acute and cutaneous porphyrias. Int J Clin Pract 56:272–278
Deybach JC, Puy H (2011) Hepatocellular carcinoma without cirrhosis: think acute hepatic porphyrias and vice versa. J Intern Med 269:521–524
Elder G, Harper P, Badminton M, Sandberg S, Deybach JC (2013) The Incidence of inherited porphyrias in Europe. JIMD 36(5):849–857
European Association for the Study of the Liver (2010) EASL clinical practice guidelines for HFE hemochromatosis. J Hepatol 53(1):3–22
Frei P, Minder EI, Corti N et al (2012) Liver transplantation because of acute liver failure due to heme arginate overdose in a patient with acute intermittent porphyria. Case Rep Gastroenterol 6:190–196
Herrick AL, McColl KEL (2005) Acute intermittent porphyria. Best Pract Res Clin Gastroenterol 19(2):235–249
Innala E, Andersson C (2011) Screening for hepatocellular carcinoma in acute intermittent porphyria: a 15-year follow-up in northern Sweden. J Intern Med 269:538–545
Puy H, Gouya L, Deybach JC (2010) Porphyrias. Lancet 375:924–937
Seth AK, Badminton MN, Mirza D, Russell S, Elias E (2007) Liver transplantation for porphyria: who, when, and how? Liver Transpl 13:1219–1227
Siddique A, Kowdley KV (2012) Review article: the iron overload syndromes. Aliment Pharmacol Ther 35(8):876–893
Siegesmund M, Van Serooskerken T, Poblete-Gutiérrez P, Frank J (2010) The acute hepatic porphyrias: current status and future challenges. Best Pract Res Clin Gastroenterol 24(5):593–605
Singal A, Parker C, Bowden C, Thapar M, Liu L, McGuire BM (2014) Liver transplantation in the management of porphyria. Hepatology 60:1082–1089
Stewart FM (2012) Review of hepatocellular cancer, hypertension and renal impairment as late complications of acute porphyria and recommendations for patient follow-up. J Clin Pathol 65:976–980
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Communicated by: John Christodoulou, MB BS PhD FRACP FRCPA
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Synopsis
Regular treatment with heme arginate in AIP may lead to iron overload and liver fibrosis.
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Barbara Willandt, Janneke G. Langendonk, Katharina Biermann, Wouter Meersseman, François D’Heygere, Christophe George, Chris Verslype, Diethard Monbaliu, and David Cassiman declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
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Barbara Willandt collected the data and wrote the first report. Janneke G. Langendonk, Katharina Biermann, Wouter Meersseman, François D’Heygere, Christophe George, Chris Verslype, Diethard Monbaliu, and David Cassiman were all involved in planning and executing the clinical follow-up and hence data collection. All authors contributed in writing or correcting/improving the final manuscript.
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Willandt, B. et al. (2015). Liver Fibrosis Associated with Iron Accumulation Due to Long-Term Heme-Arginate Treatment in Acute Intermittent Porphyria: A Case Series. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 25. JIMD Reports, vol 25. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_458
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DOI: https://doi.org/10.1007/8904_2015_458
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