Erythropoietic protoporphyria: spectrum of three cases.

BACKGROUND: Erythropoietic protoporphyria is a rare photodermatosis of childhood, and the diagnosis can be delayed. A deficient ferrochelatase enzyme leads to accumulation of protoporphyrins in the dermis, causing phototoxic burning. OBJECTIVE: To report three cases with great variability in severity of symptoms and age at diagnosis. We discuss clinical and biochemical findings, mutation analysis, and therapeutic options. METHODS: We report three cases with different degrees of photosensitivity, laboratory results, psychosocial impact, and preventive and therapeutic treatments. RESULTS: The diagnosis of erythropoietic protoporphyria was confirmed by both typical elevation of plasma porphyrins and the discovery of a mutated FECH gene. CONCLUSION: Erythropoietic protoporphyria should be suspected in any cases of childhood photosensitivity. Systemic complications are unusual. Mutation analysis confirms the diagnosis. Photoprotection is the cornerstone of treatment.

Plasma and red cell exchange transfusions for erythropoietic protoporphyria: a case report and review of the literature.

Erythropoietic protoporphyria (EPP) is a rare and usually autosomal dominant disorder characterized by ferrochelatase deficiency and accumulation of protoporphyrin in red blood cells (RBCs), skin, and liver. A small minority of patients develop severe liver dysfunction for which optimum treatment is lacking. Therapeutic plasma exchange (TPE) and RBC exchange (RCE) have been anecdotally reported to benefit patients with EPP and liver failure. A 50-year-old female with EPP developed severe liver dysfunction after knee replacement surgery and high-dose acetaminophen use. Liver biopsy showed cholestatic liver injury without fibrosis. A total of 20 TPE procedures, six RCE procedures, and then 14 more TPE procedures were performed as adjunctive therapy with the purpose of preventing progression to end-stage liver failure. After initial TPE, the plasma and RBC protoporphyrin levels decreased from 834.9 to 180.4 µg/dL (normal, ≤1 µg/dL), and from 3,905 to 2,879 µg/dL (normal, ≤80 µg/dL), respectively, without liver function improvement. RCE decreased RBC protoporphyrin levels from 2,879 to 1,225 µg/dL but plasma protoporphyrin increased from 180.4 to 1,044.1 µg/dL, and liver function failed to improve. Additional TPE again stabilized plasma protoporphyrin and improved RBC protoporphyrin levels but the patient ultimately died owing to end-stage liver disease complications. This case illustrates that TPE and RCE may improve the plasma and RBC biochemical markers of EPP activity but liver function abnormalities may persist and patients may still progress to liver failure either because of irreversible liver injury or independent pathobiological factors unrelated to EPP-induced hepatotoxicity.

Excessive erythrocyte PPIX influences the hematologic status and iron metabolism in patients with dominant erythropoietic protoporphyria.

Partial deficiency of the last enzyme of the heme biosynthetic pathway (namely ferrochelatase, FECH) in humans is responsible for erythropoietic protoporphyria (EPP). This disorder is characterised by painful photosensitivity, due to excessive production of protoporphyrin IX (PPIX) by erythrocytes. Controversial hypotheses have been proposed to explain the hematologic and iron status of EPP patients. In the present work, we explored these parameters in 55 patients with dominant EPP recruited at the French Center of Porphyrias (Colombes, France) and confirmed by molecular analysis. Our data show that erythrocyte accumulation of PPIX in EPP patients influences hematologic and iron status. Patients studied had a mild anemia and thrombocytopenia, as shown by the downward shift of hematologic parameters, which positively correlated with the amount of erythrocyte PPIX. Interestingly, erythropoiesis did not seem to be limited by iron supply in patients, since serum iron and soluble transferring (Tf) receptor (sTfR) were normal. However, iron and Tf saturation negatively correlated with erythrocyte PPIX. Moreover, and as previously described in a mouse model of EPP, we noted a positive correlation between erythrocyte PPIX and Tf levels. Altogether, these results suggest a positive effect of PPIX on the synthesis on Tf, which could facilitate the mobilization of tissue iron stores to meet erythropoiesis requirement. Based on these observations and previous results in EPP mouse model, we propose that the PPIX-liver transferrin pathway plays a role in the orchestration of iron distribution between peripheral iron stores, the spleen and the bone marrow.

Automated imaging of circulating fluorocytes for the diagnosis of erythropoietic protoporphyria: a pilot study for population screening.

OBJECTIVES: To improve the traditional fresh blood film method to a high-throughput analysis of the presence of circulating fluorescent red cells (fluorocytes) in erythropoietic protoporphyria (EPP) using an automated imaging system. METHODS: Based on the autofluorescence of protoporphyrin, we used an automatic image acquisition platform for examining fluorocytes in peripheral blood with minimal sample preparation. The image acquisition is easy-to-use under automated operations of excitation, focusing, detection and data analysis. Quality image and semi-quantitative fluorescence measurement of fluorocytes can be generated in a single step. For high-throughput analysis, the platform can image more than 200 96-well micro-plates, i.e. 19200 samples, in approximately 10 hours. Importantly, the reagent cost of analysis is negligible. RESULTS: In this pilot study, three EPP patients were diagnosed and 4000 normal individuals were screened for EPP by this method. Our results showed that the method can distinguish the overt case and asymptomatic carriers. It gives reliable evidence for rapid EPP screening. CONCLUSION: This automated imaging system provides multiple advantages that improve the traditional fresh blood film method as a more effective diagnostic tool and facilitates population screening for EPP. As fluorocytes are present in the umbilical cord blood of EPP patients, this high-throughput method can be potentially used for newborn screening of EPP.

Erythropoiesis and iron metabolism in dominant erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) results from deficiency of ferrochelatase (FECH). Accumulation of protoporphyrin IX causes life-long acute photosensitivity. Microcytic anemia occurs in 20% to 60% of patients. We investigated 178 patients with dominant EPP confirmed by molecular analysis. Erythropoiesis was impaired in all patients; all had a downward shift in hemoglobin (Hb), and the mean decreased in males by 12 g/L (1.2 g/dL). By World Health Organization criteria, 48% of women and 33% of men were anemic. Iron stores, assessed by serum ferritin (sFn), were decreased by two-thirds, but normal serum soluble transferrin receptor-1 and iron concentrations suggested that erythropoiesis was not limited by iron supply. FECH deficiency in EPP appears to lead to a steady state in which decreased erythropoiesis is matched by reduced iron absorption and supply. This response may in part be mediated by protoporphyrin, but we found no correlation between erythrocyte protoporphyrin and Hb, sFn, total iron-binding capacity, or transferrin saturation.

[Iron biochemical screening and development in infants from 6 to 24 month, by socioeconomic background, Cordoba Argentina]. / Hierro hemático y desarrollo, en niños de 6 a 24 meses de edad, según su origen social, Córdoba Argentina.

AIMS: To correlate the iron biochemical screening with cognitive and motor development, related to social background, in 6 to 24 month infants. METHODS: a population - based study of 276 children. The iron deficiency was determine by the modified criterion of Hillman (1996), combining three different screenings tests: serum ferritin, hemoglobin and erythrocyte protoporphyrin. To analyse development we used Bayley II Scale. RESULTS AND CONCLUSIONS: the anaemia was significative different (p< 0,05) between social levels, 36% in children with low socioeconomic background, 8% for the high one and iron deficiency without anaemia 42% in the total population. The motor development was homogeneous by social groups, showed 1% significative delay, 8% light delay. But the mental development shows significative differences (p<0,05) in both light and significative delay, been the must affected children with low socioeconomic background.

Hierro hemático y desarrollo en niños de 6 a 24 meses de edad, según su origen social, Córdoba, Argentina / Iron biochemical screening and development, in infants from 6 to 24 month, by socioeconomic background, Cordoba Argentina

Objetivo: Correlacionar parámetros bioquímicos de hierro y desarrollo psicomotríz, en relación al origen social, en niños de 6 a 24 meses de Córdoba, Argentina. Material y Métodos: En 276 niños se determino el estado nutricional del hierro con el criterio de Hillman, combinando ferritina, hemoglobina y protoporfirina eritrocitaria, para desarrollo Escala de Bayley 11, y variables socioeconómicas. Resultados y Conclusiones: La anemia presento diferencias (p<0.05) entre los niveles soci21es, la depleción fue 42 % en la población total. El desarrollo motor fue homogéneo en los grupos sociales; mientras que el mental presento diferencias ( p< 0.05) en retraso leve y significativo, siendo los mas afectados los niños del nivel bajo. En desarrollo y parámetros bioquímicos, el 19 % de los niños con anemia y depleción, presentaron retraso motor leve, mientras que en desarrollo mental, el retraso leve y significativo afecto en doble proporción a los niños con depleción y anemia en comparación con los niños normales.

Aims: To correlate the iron biochemical screening with cognitive and motor development, related to social background, in 6 to 24 month infants. Methods: a population - based study of 276 children. The iron deficiency was determine by the modified criterion of Hillman ( 1996), combining three different screenings tests: serum ferritin, hemoglobin and erythrocyte protoporphyrin. To analyse development we used Bayley 11 Scale. Results and conclusions: the anaemia was significative different (p< 0,05) between social levels, 36% in children with low socioeconomic background, 8% for the high one and iron deficiency without anaemia 42% in the total population. The motor development was homogeneous by social groups, showed 1 % significative delay, 8% light delay. But the mental development shows significative differences (p<0,05) in both light and significative delay, been the must affected children with low socioeconomic background.