1/13. Anaesthetic management of a patient with erythropoietic protoporphyria for ventricular septal defect closure. Erythropoietic protoporphyria (EPP) is due to a deficiency in ferrochelatase required for haem synthesis. We describe the anaesthetic management of a seven-year-old with EPP undergoing closure of a haemodynamically significant ventricular septal defect. Photosensitivity in EPP patients is triggered at wavelengths near 400 nm and light-excited porphyrins generate free radicals and singlet oxygen that lead to erythrocyte deformity and haemolysis. Stimuli that could trigger a porphyric crisis during anaesthesia and surgery were reduced by avoiding exposure to the sensitive 400 nm spectrum and using light sources covered with yellow acrylate filters in the operating room. Anaesthetic agents not previously associated with porphyric crisis were chosen. Whole blood priming of the extracorporeal circuit was performed to ensure adequate haemoglobin concentrations during the perioperative period. ( info) |
2/13. Variable effects of beta-carotene therapy in a child with erythropoietic protoporphyria. Erythropoietic protoporphyria (EPP) is an inborn error of heme biosynthesis with high levels of protoporphyrin in red cells and is characterized by mild to moderate photosensitivity. High-dose beta-carotene therapy has been reported to afford photoprotection in patients with EPP. We report the case of a 5-year-old Caucasian female with EPP who presented with a long-standing 3-year history of recurrent facial blisters and erythematous swelling and lesions of other sun-exposed areas of the skin. She was treated with a topical sunblocker (PreSun Ultra-SP45) but continued to show moderate to severe photosensitivity despite 3 months (March to May) of vigorous photoprotection. She was then started on increasing doses of beta-carotene (90-180 mg/day) over a period of 3 months (June to September) which resulted in a marked improvement of both facial and forearm lesions, but only modest improvement in her hand lesions. CONCLUSION: High-dose beta-carotene appears to provide photoprotection in erythropoietic protoporphyria, resulting in improved but highly variable tolerance to sunlight. ( info) |
3/13. Red blood cell exchange transfusion in two patients with advanced erythropoietic protoporphyria. 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. ( info) |
4/13. Combined valve and coronary surgery in a patient with erythropoietic protoporphyria. Erythropoietic protoporphyria (EPP) is an autosomal dominant disorder of heme synthesis, causing excess of protoporphyrin in blood, skin, liver, and other organs. A 58-year-old male patient with EPP underwent aortic valve replacement and a concomitant aortocoronary bypass. The patient has been followed without complications due to EPP postoperatively. Cardiac surgery can safely be performed on patients with EPP by considering close attention not to stimulate porphyrin synthesis. ( info) |
5/13. Photosensitivity and acute liver injury in myeloproliferative disorder secondary to late-onset protoporphyria caused by deletion of a ferrochelatase gene in hematopoietic cells. Late-onset erythropoietic protoporphyria (EPP) is a rare complication of myelodysplastic syndrome (MDS) but has not been described in association with a myeloproliferative disorder (MPD). EPP is normally an inherited disorder characterized by photosensitivity that starts in early childhood and results from overproduction of protoporphyrin secondary to ferrochelatase (FECH) deficiency. Severe liver disease occurs in 1% to 2% of patients. Here we report that severe photosensitivity and cholestatic liver disease in a patient with a myeloproliferative disorder was caused by excess protoporphyrin production from a clone of hematopoietic cells in which one FECH allele had been deleted. Our observations suggest that the usual explanation for the association of late-onset EPP with MPD and MDS is acquired somatic mutation of one FECH allele in bone marrow and show for the first time that the consequent overproduction of protoporphyrin may be severe enough to cause acute liver damage. ( info) |
6/13. Clinical indications for the investigation of porphyria: case examples and evolving laboratory approaches to its diagnosis in new zealand. patients with porphyria present in a diverse and unusual variety of ways and most clinicians will see only a few cases, if any, during their professional lives. Porphyria may present (1) with acute symptoms, which may be abdominal pain, neurological or psychiatric; (2) with skin rash or photosensitivity; or (3) with a putative family history. Screening for latent porphyria has been greatly facilitated by fluorescence emission scanning of plasma and by mutational analysis. Our reference laboratory has recently diagnosed several cases of the less common types of porphyria, which we postulate is due to the availability of these methods and to the changing population of new zealand. Accurate screening and diagnosis of porphyria is important, as an acute porphyric attack is life-threatening and preventable. Retrospective diagnosis may be difficult. ( info) |
7/13. Exonic deletions as a cause of erythropoietic protoporphyria. Erythropoietic protoporphyria (EPP) is an inherited disorder that results from partial deficiency of ferrochelatase (FECH), the terminal enzyme of haem biosynthesis. Current methods that examine the exons and their flanking regions of the FECH gene fail to identify mutations in about one in seven of families with EPP. The presence in some families of intragenic deletions that are not identifiable by current methods for sequencing the FECH gene may partly explain the low sensitivity of mutation detection in EPP. Here we describe the identification by gene dosage analysis of a deletion of exons 3 and 4 in a family with EPP in whom a mutation had not been found by sequencing-based methods. ( info) |
8/13. Acquired erythropoietic protoporphyria as a result of myelodysplasia causing loss of chromosome 18. We report a patient aged 73 years, who developed erythropoietic protoporphyria with typical photosensitivity, at the same time as she was diagnosed as having myelodysplastic syndrome. The myelodysplastic clone in her bone marrow completely lacked one of the two copies of chromosome 18. As chromosome 18 is the locus of the ferrochelatase gene, we postulate that this chromosomal deletion led to reduced synthesis of the enzyme in the bone marrow clone, so causing the porphyria. The nature of the remaining ferrochelatase allele was examined by polymorphism analysis and we discuss the insights that this patient's genotype may reveal about the pathogenesis of porphyria in myelodysplasia. ( info) |
9/13. Sequential liver and bone marrow transplantation for treatment of erythropoietic protoporphyria. 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. ( info) |
10/13. ferrochelatase deficiency in the bone marrow in a syndrome of congenital hypochromic microcytic anemia, hyperferremia, and iron overload of the liver. Two sisters had congenital hypochromic microcytic anemia with hyperferremia, heavy iron deposits in the liver, and reduced bone marrow iron. Liver ferrochelatase activity was within normal limits, but in the bone marrow ferrochelatase activity was only 20% of that in healthy controls. There were no findings suggestive of lead intoxication, sideroblastic anemia, or erythropoietic protoporphyria. ( info) |