JIMD Reports, Volume 25

Barbara Willandt, Janneke G. Langendonk, Katharina Biermann, Wouter Meersseman, François D’Heygere, Christophe George, Chris Verslype, Diethard Monbaliu, David Cassiman, Willandt, Barbara, Langendonk, Janneke G., Biermann, Katharina, Meersseman, Wouter, D’Heygere, François, George, Christophe, Verslype, Chris, Monbaliu, Diethard, Cassiman, David

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. 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.