BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare, autosomal dominant genetic disorder caused by the decreased or absent activity of ferrochelatase, the final enzyme in the heme biosynthetic pathway. This enzyme defect in peripheral blood progenitor cells leads to the accumulation of protoporphyrin deposits in multiple tissues. Plasmapheresis has been previously reported as an adjunctive therapy for patients with advanced hepatic EPP. Because the concentration of protoporphyrins is severalfold higher inside the red blood cell (RBC) compared to plasma, it was hypothesized that RBC exchange therapy might absorb excess protoporphyrins from the plasma and serve as an effective therapy to reduce protoporphyrin load in patients with advanced hepatic EPP. The effectiveness of RBC exchange plus hematin versus plasmapheresis plus hematin in two patients with advanced hepatic EPP is reported. STUDY DESIGN AND METHODS: Two patients with advanced hepatic EPP were treated with RBC exchange and plasmapheresis in the setting of recurrent disease in the graft (Patient 1) or preparation for liver transplantation (Patient 2). In vitro studies were performed to test transport of protoporphyrins from patients' plasma to normal RBCs. RESULTS: Compared with plasmapheresis, RBC exchange was more effective, for the duration of the therapy, in reducing blood levels of protoporphyrins. Liver function tests, however, showed only a modest improvement during therapy. In vitro extracellular protoporphyrin were rapidly adsorbed into normal RBCs. CONCLUSION: Neither RBC exchange nor plasmapheresis prevented progressive hepatic deterioration in advanced hepatic EPP despite a significant decrease in protoporphyrin levels.
BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare, autosomal dominant genetic disorder caused by the decreased or absent activity of ferrochelatase, the final enzyme in the heme biosynthetic pathway. This enzyme defect in peripheral blood progenitor cells leads to the accumulation of protoporphyrin deposits in multiple tissues. Plasmapheresis has been previously reported as an adjunctive therapy for patients with advanced hepatic EPP. Because the concentration of protoporphyrins is severalfold higher inside the red blood cell (RBC) compared to plasma, it was hypothesized that RBC exchange therapy might absorb excess protoporphyrins from the plasma and serve as an effective therapy to reduce protoporphyrin load in patients with advanced hepatic EPP. The effectiveness of RBC exchange plus hematin versus plasmapheresis plus hematin in two patients with advanced hepatic EPP is reported. STUDY DESIGN AND METHODS: Two patients with advanced hepatic EPP were treated with RBC exchange and plasmapheresis in the setting of recurrent disease in the graft (Patient 1) or preparation for liver transplantation (Patient 2). In vitro studies were performed to test transport of protoporphyrins from patients' plasma to normal RBCs. RESULTS: Compared with plasmapheresis, RBC exchange was more effective, for the duration of the therapy, in reducing blood levels of protoporphyrins. Liver function tests, however, showed only a modest improvement during therapy. In vitro extracellular protoporphyrin were rapidly adsorbed into normal RBCs. CONCLUSION: Neither RBC exchange nor plasmapheresis prevented progressive hepatic deterioration in advanced hepatic EPP despite a significant decrease in protoporphyrin levels.
Authors: Harushige Ozaki; Sami S Zoghbi; Jinsoo Hong; Ajay Verma; Victor W Pike; Robert B Innis; Masahiro Fujita Journal: Synapse Date: 2010-08 Impact factor: 2.562
Authors: Joanna K Dowman; Briget K Gunson; Darius F Mirza; Mike N Badminton; Philip N Newsome Journal: J Inherit Metab Dis Date: 2011-02-08 Impact factor: 4.982