Hepatobiliary implications and complications in protoporphyria, a 20-year study

Doss, M.; Frank, M

doi:10.1016/s0009-9120(89)80081-5

Cited by 120 publications

(85 citation statements)

References 33 publications

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“…1,2,[4][5][6][7] The therapy of EPP is often limited to supportive care and is only partially successful, especially in the severe forms. This monogenic disorder starts early in infancy and represents a good candidate for gene therapy in severe forms since the genetic defect is well characterized at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells

Fontanellas

Méndez²,

Mazurier³

et al. 2001

Gene Ther

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Section: Introductionmentioning

confidence: 99%

Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells

Fontanellas

Méndez²,

Mazurier³

et al. 2001

Gene Ther

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“…The principle clinical manifestation is photosensitivity, which is caused by the photoreactive properties of protoporphyrin circulating in dermal blood vessels and/or deposited in skin (5,6). Hepatobiliary disease may also occur (7,8), and some patients develop progressive liver failure that necessitates liver transplantation (9)(10)(11). The liver damage is caused by the toxic effect of protoporphyrin on liver structure and function (12,13).…”

Section: Introductionmentioning

confidence: 99%

Molecular defects in ferrochelatase in patients with protoporphyria requiring liver transplantation.

Bloomer¹,

Bruzzone²,

Zhu³

et al. 1998

J. Clin. Invest.

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Protoporphyria is a genetic disorder in which a deficiency of mitochondrial ferrochelatase activity causes accumulation of protoporphyrin that produces severe liver damage in some patients. In this study, mutations of the ferrochelatase gene were examined in eight unrelated patients who had liver transplantation. RNA was prepared from liver and/ or lymphoblasts, and specific reverse transcriptase-nested polymerase chain reactions amplified and sequenced ferrochelatase cDNAs. Products shorter than normal resulted from an exon 3 deletion in three patients, exon 10 deletion in two, exon 2 deletion in one, and deletion of five nucleotides in exon 5 in one. Sequence of normal-size products revealed no other mutations. Western blot showed a reduced quantity of normal-size ferrochelatase protein in protoporphyria liver compared with normal liver (19-51%, mean 32% of normal). Levels of the mitochondrial protein F 1 -ATPase ␤ -subunit were not decreased to a similar degree. Liver ferrochelatase activity was reduced more than could be explained by the decrease in ferrochelatase protein (4-20%, mean 9% of normal). These results establish genetic heterogeneity in the most severe phenotype of protoporphyria. However, the gene mutations found share the property of causing a major structural alteration in the ferrochelatase protein.

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“…5,6 Some patients also develop liver disease that is caused by the toxic effect of protoporphyrin on hepatobiliary structure and function. 7 Experimental studies have shown that protoporphyrin impairs bile formation and alters activity of hepatic membrane-bound enzymes. 8,9 In addition, studies in a mouse model of EPP indicate that toxic bile may be formed, which damages bile duct epithelium and causes biliary fibrosis.…”

mentioning

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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Hepatobiliary implications and complications in protoporphyria, a 20-year study

Cited by 120 publications

References 33 publications

Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells

Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells

Molecular defects in ferrochelatase in patients with protoporphyria requiring liver transplantation.

Liver transplantation for erythropoietic protoporphyria liver disease

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