Benefits of Chronic Plasmapheresis and Intravenous Heme-Albumin in Erythropoietic Protoporphyria After Orthotopic Liver Transplantation12

Khoa, Do Vo Anh; Banner, Barbara F.; Katz, Eliezer; Szymanski, Irma O.; Bonkovsky, Herbert L.

doi:10.1097/00007890-200202150-00024

Cited by 49 publications

(39 citation statements)

References 8 publications

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“…The histology of his liver (Figure 2A) resembled that reported for allografts after orthotopic transplantation for EPP liver disease, where liver disease may recur within 9 months of exposure of a previously normal liver to excess protoporphyrin. 17,18 Our findings, together with previous reports of gross abnormalities of chromosome 18 in bone marrow in some patients with RARS or MDS and EPP, 7,9 show that an acquired somatic mutation of one FECH allele in hematopoietic cells is the usual explanation for the association of late-onset EPP with MPD and MDS, both conditions in which there is genetic instability. 19,20 Furthermore, management of this uncommon complication of MDS and MPD should include measures to prevent fatal protoporphyric liver disease.…”

Section: Resultssupporting

confidence: 77%

Photosensitivity and acute liver injury in myeloproliferative disorder secondary to late-onset protoporphyria caused by deletion of a ferrochelatase gene in hematopoietic cells

Goodwin

Kell

Laidler

et al. 2006

Blood

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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. IntroductionErythropoietic protoporphyria (EPP) is an uncommon inherited disorder of heme biosynthesis that results from partial deficiency of ferrochelatase (FECH). It is characterized clinically by childhood onset of lifelong photosensitivity and biochemically by overproduction of protoporphyrin in erythropoietic cells with accumulation of protoporphyrin in erythrocytes, plasma, skin, and liver. 1 Clinical expression of EPP normally requires inheritance of an FECH mutation trans to a lowexpression FECH allele, 2-4 which is present in 13% of the United Kingdom population. 4 In 1% to 2% of patients with EPP, deposition of protoporphyrin in the liver leads to progressive liver failure, usually after at least a decade of photosensitivity. 1,5,6 Late onset of photosensitivity is rare in EPP. 1 Only 10 patients have been reported in whom symptoms started after the age of 40 years, 7-10 7 of whom also had refractory anemia with ring sideroblasts (RARS) or other myelodysplastic syndromes (MDSs). In one patient, EPP was recently shown to be caused by proliferation of a clone of hematopoietic cells in which one allele of the FECH gene had been deleted. 9 Here we describe a patient with a myeloproliferative disorder (MPD) who developed severe photosensitivity and cholestatic liver disease. We postulated that these complications were caused by an acquired somatic mutation of the FECH gene in his hematopoietic cells. Study designA 62-year-old man was diagnosed with polycythemia vera (PV) and hyperuricemia (hemoglobin concentration, 17.5 g/L; hematocrit, 0.513 [51.3%]; leukocyte count, 11.1 ϫ 10 9 /L; platelet count, 191 ϫ 10 9 /L; red cell volume, 34.2 mL/kg [136% of predicted]; plasma volume, 34.4 mL/kg [92.6% of predicted]). Bone marrow examination was consistent with a myeloproliferative disorder (MPD), showing increased cellularity, no excess blasts, no ringed sideroblasts, and normal cytogenetics. He was treated with hydroxyurea, venesections, and allopurinol. Thirty-three months later, an increase in his white cell count (73 ϫ 10 9 /L; 79% neutr...

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Section: Resultssupporting

confidence: 77%

Photosensitivity and acute liver injury in myeloproliferative disorder secondary to late-onset protoporphyria caused by deletion of a ferrochelatase gene in hematopoietic cells

Goodwin

Kell

Laidler

et al. 2006

Blood

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“…The laboratory data at the time of transplant included an average total bilirubin of 13.2 mg/dl (range, 4.2-35), creatinine of 0.9 mg/dl (range, 0.5-2.6), and INR (measured or estimated from available prothrombin times) of 1.6 (range, 1.0-2.1). 33 The estimated MELD score in the patients prior to transplant was 21 (range, [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”

Section: Resultsmentioning

confidence: 99%

“…28 To treat EPP crisis and neuropathy, intravenous hematin therapy with or without plasmapheresis has been used. [29][30][31][32] The largest previous study, which reported the complications and outcomes of nine patients transplanted for EPP, was published in 1996 and showed that intermediate survival was good. 18 The present study includes those nine patients and adds eleven others who have been transplanted in the United States.…”

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confidence: 99%

Liver transplantation for erythropoietic protoporphyria liver disease

et al. 2005

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In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival. (Liver Transpl 2005;11:1590-1596.)

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“…These unsatisfactory outcomes for NLOD resulted from not only the growth retardation but also the fact that extrahepatic manifestations of these disorders disadvantageously affected the postoperative course of these patients. Recently, some therapeutic options for these extrahepatic manifestations of NLOD after LT have been reported to be efficacious (10,(20)(21)(22)(23). However, all of these reported therapies were symptomatic treatments and the evidence of their efficacy seemed to be anecdotal.…”

Section: Discussionmentioning

confidence: 99%

“…Whether or not each donor was a heterozygote for the recipient's disorder was determined by the mode of inheritance of each disorder (autosomal recessive inheritance for WD (3), TTI (9), GSD (10), PPA (4), MMA (4), CNSI (4) and BASD (11), autosomal dominant for EPP (12) and X-linked for OTCD (4)). In addition to our standard donor selection criteria, which have been described in detail elsewhere (13,14), some donors who were considered or suspected to be heterozygous carriers for their respective recipient's disorder underwent the following additional medical tests according to the disorder in question: for WD cases, assays for serum ceruloplasmin levels, urine copper excretion and the presence of Kayser-Fleischer corneal ring; for OTCD cases, quantitative serum amino acid analysis (QAAA) and allopurinol loading test (15,16); and for cases of PPA or MMA, serum propionic acid or methylmalonate level and the presence of metabolic acidosis confirmed by blood gas analysis.…”

Section: Methodsmentioning

confidence: 99%

Living Donor Liver Transplantation for Pediatric Patients with Inheritable Metabolic Disorders

Morioka

Kasahara

Takada

et al. 2005

American Journal of Transplantation

104

111

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Forty-six pediatric patients who underwent living donor liver transplantation (LDLT) using parental liver grafts for inheritable metabolic disorders (IMD) were evaluated to determine the outcomes of the surgery, decisive factors for post-transplant patient survival and the impact of using donors who were heterozygous for the particular disorder. Disorders included Wilson disease (WD, n = 21), ornithine transcarbamylase deficiency (OTCD, n = 6), tyrosinemia type I (TTI, n = 6), glycogen storage disease (GSD, n = 4), propionic acidemia (PPA, n = 3), methylmalonic acidemia (MMA, n = 2), Crigler-Najjar syndrome type I (CNSI, n = 2), bile acid synthetic defect (BASD, n = 1) and erythropoietic protoporphyria (EPP, n = 1). The post-transplant cumulative patient survival rates were 86.8 and 81.2% at 1 and 5 years, respectively. Posttransplant patient survival and recovery of the growth retardation were significantly better in the liveroriented diseases (WD, OTCD, TTI, CNSI and BASD) than in the non-liver-oriented diseases (GSD, PPA, MMA and EPP) and pre-transplant growth retardation disadvantageously affected post-transplant outcomes. Although 40 of 46 donors were considered heterozygous for each disorder, neither mortality nor morbidity related to the heterozygosis has been observed. LDLT using parental donors can be recommended as an effective treatment for pediatric patients with IMD. In the non-liver-oriented diseases, however, satisfactory outcomes were not obtained by hepatic replacement alone.

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Benefits of Chronic Plasmapheresis and Intravenous Heme-Albumin in Erythropoietic Protoporphyria After Orthotopic Liver Transplantation12

Cited by 49 publications

References 8 publications

Photosensitivity and acute liver injury in myeloproliferative disorder secondary to late-onset protoporphyria caused by deletion of a ferrochelatase gene in hematopoietic cells

Photosensitivity and acute liver injury in myeloproliferative disorder secondary to late-onset protoporphyria caused by deletion of a ferrochelatase gene in hematopoietic cells

Liver transplantation for erythropoietic protoporphyria liver disease

Living Donor Liver Transplantation for Pediatric Patients with Inheritable Metabolic Disorders

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