Erythrocyte Protoporphyrin and Iron Uptake in Erythropoietic Protoporphyria

1971 ◽  
Vol 41 (4) ◽  
pp. 363-370 ◽  
Author(s):  
K. G. A. Clark ◽  
D. C. Nicholson
Keyword(s):  
Fluorescence Microscopy ◽  
Iron Uptake ◽  
Cell Column ◽  
Erythropoietic Protoporphyria ◽  
Mutual Dependence ◽  
Erythrocyte Protoporphyrin

1. Erythrocytes from patients with erythropoietic protoporphyria (E.P.P.) were incubated with radioactive iron, washed and centrifuged. Serial layers were removed from the packed cell columns. The radioactivity and protoporphyrin content of each layer was measured. Blood and marrow aspirates were examined by fluorescence microscopy. 2. The youngest erythrocytes were most fluorescent and contained most protoporphyrin. The amounts present in the cells of different layers progressively decreased from top to bottom of the packed cell column. It is concluded that the protoporphyrin content decreases during the life of the erythrocytes, probably by a process of elution. 3. Although little 59Fe entering the erythrocytes is incorporated into haem, a relationship was observed between iron uptake and protoporphyrin content, which may not be entirely due to aging. This may reflect a mutual dependence of both variables on haem feed-back control. 4. Fluorescence of normoblasts was not detected, indicating that the chief accumulation of porphyrin occurs soon after loss of the nucleus. A hypothesis is suggested to explain these findings.

scholarly journals Light-induced release of protoporphyrin, but not of zinc protoporphyrin, from erythrocytes in a patient with greatly elevated erythrocyte protoporphyrin

Blood ◽  
1983 ◽  
Vol 62 (4) ◽  
pp. 846-851 ◽  
Author(s):  
S Sandberg ◽  
I Talstad ◽  
G Hovding ◽  
N Bjelland
Keyword(s):  
Iron Deficiency ◽  
Malignant Lymphoma ◽  
Lead Intoxication ◽  
Zinc Protoporphyrin ◽  
Erythropoietic Protoporphyria ◽  
Erythrocyte Protoporphyrin

Abstract A patient with greatly increased erythrocyte protoporphyrin, but normal porphyrins in urine and feces, is described. The patient later developed a malignant lymphoma, and the reason why she accumulated protoporphyrin in her erythrocytes is not known. The protoporphyrin in the erythrocytes consisted of two types of protoporphyrin, free protoporphyrin (30%) and zinc protoporphyrin (70%). Upon irradiation of erythrocytes in the absence of albumin, protoporphyrin and zinc protoporphyrin, which were both bound to hemoglobin, were released. In contrast, when the irradiation was carried out in the presence of albumin, the photohemolysis was negligible, and there was release of free protoporphyrin, but not of zinc protoporphyrin, from the erythrocytes. In vivo albumin is present in the plasma and the results may help to explain why patients with erythropoietic protoporphyria (erythrocytes containing free protoporphyrin) are photosensitive, whereas patients with lead intoxication and iron deficiency (erythrocytes containing zinc protoporphyrin) are not.

scholarly journals hem6: an ENU-induced recessive hypochromic microcytic anemia mutation in the mouse

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4308-4313 ◽  
Author(s):  
Meng Tian ◽  
Dean R. Campagna ◽  
Lanette S. Woodward ◽  
Monica J. Justice ◽  
Mark D. Fleming
Keyword(s):  
Iron Uptake ◽  
Autosomal Recessive ◽  
Aminolevulinic Acid ◽  
Microcytic Anemia ◽  
Zinc Protoporphyrin ◽  
Mouse Mutant ◽  
Erythropoietic Protoporphyria ◽  
Enzymatic Assays ◽  
Hypochromic Microcytic Anemia ◽  
Uptake Studies

AbstractMouse models have proven invaluable for understanding erythropoiesis. Here, we describe an autosomal recessive, inherited anemia in the mouse mutant hem6. Hematologic and transplantation analyses reveal a mild, congenital, hypochromic, microcytic anemia intrinsic to the hematopoietic system that is associated with a decreased red blood cell zinc protoporphyrin to heme ratio, indicative of porphyrin insufficiency. Intercross matings show that hem6 can suppress the porphyric phenotype of mice with erythropoietic protoporphyria (EPP). Furthermore, iron uptake studies in hem6 reticulocytes demonstrate defective incorporation of iron into heme that can be partially corrected by the addition of porphyrin precursors. Gene expression and enzymatic assays indicate that erythroid 5-aminolevulinic acid synthase (Alas2) is decreased in hem6 animals, suggesting a mechanism that could account for the anemia. Overall, these data lead to the hypothesis that hem6 encodes a protein that directly or indirectly regulates the expression of Alas2.

Intravenous Hemin as Prophylaxis of Allograft Function Following Second Liver Transplant for Erythropoietic Protoporphyria.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3677-3677
Author(s):  
Gary J. Schiller ◽  
Leonard Goldstein ◽  
Richard Finn ◽  
Ronald Busuttil
Keyword(s):  
Liver Transplantation ◽  
Alkaline Phosphatase ◽  
Liver Transplant ◽  
Orthotopic Liver Transplantation ◽  
Hepatic Failure ◽  
Graft Function ◽  
Erythropoietic Protoporphyria ◽  
Erythrocyte Protoporphyrin ◽  
First Case ◽  
The Impact

Abstract Erythropoietic protoporphyria (EPP) is a rare disorder of heme biosynthesis caused by an inherited deficiency of mitochondrial ferrochelatase. This deficiency results in accumulation of protoporphyrin, a heme precursor, in bone marrow, skin, nervous system, and liver. In some patients, toxic levels of protoporphyrins in the liver cause chronic liver disease, cirrhosis, and hepatic failure. Liver transplantation is the only treatment available; however, the risk of allograft dysfunction is high as a result of continued, excessive protoporphyrin production due to the underlying systemic enzyme deficiency. We present the case of a 40 year-old man with EPP, diagnosed at age 6, who underwent orthotopic liver transplantation (OLT) at age 25. By age 31, biopsy-proven recurrent EPP with liver dysfunction was identified in the allograft with subsequent hepatic failure seven years later at age 38. A second liver transplant was complicated by a biliary anastomotic leak requiring further surgery and prolonged hospitalization. Six months prior to a second liver transplant, the patient was started on 4 mg/kg hemin infusions every week; following second liver transplant, the frequency was increased to twice weekly to maintain graft function. Infusions have been well tolerated and administered at home through a central venous catheter and there has been no evidence of iron overload. Three months following second transplant, blood alkaline phosphatase, ALT, AST, and bilirubin were 1009, 53, 64, and 11.5, respectively. Fourteen months after the second allograft, these levels are 234, 65, 65, and 1.2, respectively. Prior to hemin therapy, erythrocyte protoporphyrin level was 6600 mg/dl and was 5573 mg/dl immediately before second allograft. With twice weekly hemin, erythrocyte protoporphyrin level fourteen months after transplantation is 1240 mg/dl - greatly reduced but still elevated above the normal range. A liver biopsy three months after the second allograft showed cholestasis and biliary obstruction consistent with recurrent porphyria, but no subsequent biopsy has been performed yet despite improvement in alkaline phosphatase, bilirubin, and transaminase levels. This case study confirms an earlier report of clinical graft stabilization with hemin infusions after orthotopic liver transplantation for erythropoietic protoporphyria (Dellon et al., Transplantation2002; 73:911–5) and to our knowledge is the first case of long-term hemin use to maintain the integrity of a second liver allograft. Further follow-up and biopsy will be needed to determine the impact of this strategy on preserving graft function.

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