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Joseph R. Bloomer - One of the best experts on this subject based on the ideXlab platform.
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pitfalls in erythrocyte Protoporphyrin measurement for diagnosis and monitoring of protoporphyrias
Clinical Chemistry, 2015Co-Authors: Eric Gou, Joseph R. Bloomer, Manisha Balwani, Montgomery D Bissell, Herbert L Bonkovsky, Robert J Desnick, Hetanshi Naik, John D Phillips, Ashwani K Singal, Bruce WangAbstract:BACKGROUND: Laboratory diagnosis of erythropoietic protoporphyria (EPP) requires a marked increase in total erythrocyte Protoporphyrin (300–5000 μg/dL erythrocytes, reference interval <80 μg/dL) and a predominance (85%–100%) of metal-free Protoporphyrin [normal, mostly zinc Protoporphyrin (reference intervals for the zinc Protoporphyrin proportion have not been established)]; plasma porphyrins are not always increased. X-linked protoporphyria (XLP) causes a similar increase in total erythrocyte Protoporphyrin with a lower fraction of metal-free Protoporphyrin (50%–85% of the total). CONTENT: In studying more than 180 patients with EPP and XLP, the Porphyrias Consortium found that erythrocyte Protoporphyrin concentrations for some patients were much higher (4.3- to 46.7-fold) than indicated by previous reports provided by these patients. The discrepant earlier reports, which sometimes caused the diagnosis to be missed initially, were from laboratories that measure Protoporphyrin only by hematofluorometry, which is intended primarily to screen for lead poisoning. However, the instrument can calculate results on the basis of assumed hematocrits and reports results as “free” and “zinc” Protoporphyrin (with different reference intervals), implying separate measurements of metal-free and zinc Protoporphyrin. Such misleading reports impair diagnosis and monitoring of patients with protoporphyria. SUMMARY: We suggest that laboratories should prioritize testing for EPP and XLP, because accurate measurement of erythrocyte total and metal-free Protoporphyrin is essential for diagnosis and monitoring of these conditions, but less important for other disorders. Terms and abbreviations used in reporting erythrocyte Protoporphyrin results should be accurately defined.
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Pitfalls in Erythrocyte Protoporphyrin Measurement for Diagnosis and Monitoring of Protoporphyrias
Clinical chemistry, 2015Co-Authors: Eric Gou, Joseph R. Bloomer, Manisha Balwani, Herbert L Bonkovsky, Robert J Desnick, Hetanshi Naik, John D Phillips, Ashwani K Singal, D. Montgomery Bissell, Bruce WangAbstract:BACKGROUND: Laboratory diagnosis of erythropoietic protoporphyria (EPP) requires a marked increase in total erythrocyte Protoporphyrin (300–5000 μg/dL erythrocytes, reference interval
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Sequential liver and bone marrow transplantation for treatment of erythropoietic protoporphyria.
Pediatrics, 2006Co-Authors: Elizabeth B. Rand, Nancy Bunin, William J. Cochran, Eduardo Ruchelli, Kim M. Olthoff, Joseph R. BloomerAbstract:Erythropoietic protoporphyria is a disorder of heme synthesis in which deficient ferrochelatase activity leads to excess production and biliary excretion of Protoporphyrin. The main clinical features, photosensitivity and hepatobiliary disease that may progress to liver failure, are caused by the toxicity of Protoporphyrin. Liver transplantation has been used to treat liver failure in erythropoietic protoporphyria, but excess production of Protoporphyrin by the bone marrow continues causing recurrence of liver disease in the majority of patients. This is the first report of successful sequential liver and bone marrow transplantation in a patient with liver failure as a result of erythropoietic protoporphyria. This combination corrected the severe phenotype, resolving the severe photosensitivity and halting erythropoietic protoporphyria associated liver graft injury. Splenectomy seemed to facilitate the successful bone marrow transplant.
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Hepatic Protoporphyrin metabolism in patients with advanced protoporphyric liver disease.
The Yale journal of biology and medicine, 1997Co-Authors: Joseph R. BloomerAbstract:Protoporphyria is a genetic disorder in which liver damage is caused by the toxic effect of Protoporphyrin accumulation in the liver. In this study Protoporphyrin was measured in the resected livers of 7 patients who had liver transplantation and an additional patient from whom liver tissue was obtained post mortem. Comparison of liver, erythrocyte and serum Protoporphyrin levels demonstrated a marked gradient between these compartments: erythrocyte, 5781 +/- 655 micrograms/dl; serum, 384 +/- 102 micrograms/dl; liver 377,238 +/- 55,568 micrograms/100 gm wet weight, (mean +/- SE). Protoporphyrin levels in bile of 3 patients were 55,559, and 1,153 micrograms/dl, indicating a gradient between liver and bile as well. Examination of the livers by polarization microscopy and electron microscopy demonstrated Protoporphyrin pigment crystals. In one patient who had recurrent liver disease after transplantation, the Protoporphyrin concentration in the graft at the time of death was similar to that in the resected liver. These data indicate that liver Protoporphyrin levels in patients with advanced protoporphyric liver disease are much higher than levels in blood and bile, in part because Protoporphyrin forms crystalline deposits in liver tissue. Thus, progressive hepatic accumulation of Protoporphyrin occurs in the face of impaired biliary excretion. An intrinsic defect in hepatic excretion of Protoporphyrin is probably not necessary for this condition to develop because liver disease can occur in the graft following transplantation.
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Hematin Therapy in Children With Protoporphyric Liver Disease
Journal of Pediatric Gastroenterology and Nutrition, 1996Co-Authors: Carol Potter, Naser Tolaymat, Robert Bobo, Harvey Sharp, Jeffrey M. Rank, Joseph R. BloomerAbstract:Protoporphyria is a genetic disorder of porphyrin metabolism in which a deficiency of ferrochelatase activity causes excessive accumulation and excretion of Protoporphyrin (1,2). Protoporphyrin is excreted in bile, and its deposition in the liver impairs hepatic structure and function (3,4). As a co
D. Burrows - One of the best experts on this subject based on the ideXlab platform.
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Erythropoietic protoporphyria, transfusion therapy and liver disease
The British journal of dermatology, 1992Co-Authors: D. J. Todd, M.e. Callender, E.e. Mayne, M. Walsh, D. BurrowsAbstract:A 28-year-old man who had suffered from erythropoietic protoporphyria since infancy was referred because of worsening photosensitivity. Conventional therapy with beta-carotene, terfenadine and topical sunscreens was ineffective or not tolerated, and he was treated with transfusions of washed packed cells. Unexpectedly, his photosensitivity deteriorated further, his whole blood Protoporphyrin levels doubled and he developed abnormal liver function tests. This is the first report of such an adverse response to blood transfusion therapy for erythropoietic protoporphyria and may have been related to subclinical hepatitis or the increased iron load associated with blood transfusion.
Kim M. Olthoff - One of the best experts on this subject based on the ideXlab platform.
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erythropoietic protoporphyria in an adult with sequential liver and hematopoietic stem cell transplantation a case report
American Journal of Transplantation, 2018Co-Authors: Annika L Windon, Rashmi Tondon, Nathan Singh, Samir Abugazala, David L Porter, Eric J Russell, Colleen Cook, Elaine Lander, Georgeine Smith, Kim M. OlthoffAbstract:Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthesis pathway resulting in the accumulation of Protoporphyrins in the blood, erythrocytes, and other tissues. Because of a gene mutation in the FECH gene, ferrochelatase, the enzyme involved in the final step of heme synthesis, is deficient in these patients. Although the major symptom of this disorder is photosensitivity, rarely, it can cause progressive liver disease requiring liver transplantation (LT). However, LT is not curative and only bone marrow transplantation (BMT) can correct the underlying enzymatic defect. Because liver disease results from accumulation of Protoporphyrin in the liver, LT without hematopoietic stem cell transplantation leaves the new liver at risk for similar EPP-related damage. A handful of pediatric patients undergoing sequential LT and stem cell transplantation have been described in the literature; however, to date none has been described in detail in adults. We report a case of an adult male with EPP and liver failure who successfully underwent a sequential liver and hematopoietic stem cell transplantation (HSCT).
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Sequential liver and bone marrow transplantation for treatment of erythropoietic protoporphyria.
Pediatrics, 2006Co-Authors: Elizabeth B. Rand, Nancy Bunin, William J. Cochran, Eduardo Ruchelli, Kim M. Olthoff, Joseph R. BloomerAbstract:Erythropoietic protoporphyria is a disorder of heme synthesis in which deficient ferrochelatase activity leads to excess production and biliary excretion of Protoporphyrin. The main clinical features, photosensitivity and hepatobiliary disease that may progress to liver failure, are caused by the toxicity of Protoporphyrin. Liver transplantation has been used to treat liver failure in erythropoietic protoporphyria, but excess production of Protoporphyrin by the bone marrow continues causing recurrence of liver disease in the majority of patients. This is the first report of successful sequential liver and bone marrow transplantation in a patient with liver failure as a result of erythropoietic protoporphyria. This combination corrected the severe phenotype, resolving the severe photosensitivity and halting erythropoietic protoporphyria associated liver graft injury. Splenectomy seemed to facilitate the successful bone marrow transplant.
Zbigniew M Szczepiorkowski - One of the best experts on this subject based on the ideXlab platform.
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red blood cell exchange transfusion in two patients with advanced erythropoietic protoporphyria
Transfusion, 2005Co-Authors: Quentin Eichbaum, Walter H Dzik, Raymond T Chung, Zbigniew M SzczepiorkowskiAbstract: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.
D. J. Todd - One of the best experts on this subject based on the ideXlab platform.
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Erythropoietic protoporphyria, transfusion therapy and liver disease
The British journal of dermatology, 1992Co-Authors: D. J. Todd, M.e. Callender, E.e. Mayne, M. Walsh, D. BurrowsAbstract:A 28-year-old man who had suffered from erythropoietic protoporphyria since infancy was referred because of worsening photosensitivity. Conventional therapy with beta-carotene, terfenadine and topical sunscreens was ineffective or not tolerated, and he was treated with transfusions of washed packed cells. Unexpectedly, his photosensitivity deteriorated further, his whole blood Protoporphyrin levels doubled and he developed abnormal liver function tests. This is the first report of such an adverse response to blood transfusion therapy for erythropoietic protoporphyria and may have been related to subclinical hepatitis or the increased iron load associated with blood transfusion.
