Erythropoietic Protoporphyria

Abstract

A 34-year-old woman with a history of photosensitivity reaction was admitted to our hospital for epigastralgia and jaundice, which had persisted for 1 month. She had no history of alcohol consumption, and had regularly been taking ferric oxide for the treatment of anemia. Physical examination revealed that the skin and conjunctiva were icteric; abdominal tenderness and palpable liver and spleen were noted. Blood examination revealed anemia (hemoglobin 9.2 g/dL), and liver dysfunction (international normalized ratio, 1.54; total bilirubin, 4.4 mg/dL; alanine aminotransferase, 90 IU/L; y-glutamyltransferase, 159 IU/L). The results of serologic examination for hepatitis B and C virus were negative. An abdominal computed tomography scan showed hepatosplenomegaly. For further investigation, needle biopsy of the liver was performed.On hematoxylin-eosin staining (Figure A), the liver specimen showed slightly distorted lobular architecture. It contained deposits of dark reddish-brown pigment localized in the cytoplasm of the hepatocytes and Kupffer cells in the lumen of the dilated canaliculi and/or interlobular ducts. All the deposits exhibited striking birefringence on polarization microscopic examination (Figure B). Characteristically, some globular deposits appeared bright red and had a centrally-located Maltese cross (arrow). Further, a significant increase was noted in the protoporphyrin levels in the patient's red blood cell count (8578 μg/dL). These findings led to the diagnosis of erythropoietic protoporphyria (EPP).EPP is an inborn error of haem biosynthesis caused by mutations in the gene encoding the mitochondrial enzyme ferrochelatase, which is the final enzyme in the haem biosynthetic pathway. Defects in ferrochelatase lead to an excess of protoporphyrin in the plasma, which in turn induces photosensitivity. Liver damage occurs due to cholestasis caused by excess protoporphyrin and/or exposure to protoporphyrin itself. Protoporphyrin-induced hepatotoxicity is a rare condition occurring in 1%–5% of EPP patients1Anstey A.V. Hift R.J. Liver disease in erythropoietic protoporphyria: insights and implications for management.Gut. 2007; 56: 1009-1018PubMed Google Scholar; however, in patients with deteriorating liver disease, EPP may be irreversible, and such patients require liver transplantation.2McGuire B.M. Bonkovsky H.L. Carithers R.L. et al.Liver transplantation for erythropoietic protoporphyria liver disease.Liver Transpl. 2005; 11: 1590-1596Crossref PubMed Scopus (111) Google Scholar A 34-year-old woman with a history of photosensitivity reaction was admitted to our hospital for epigastralgia and jaundice, which had persisted for 1 month. She had no history of alcohol consumption, and had regularly been taking ferric oxide for the treatment of anemia. Physical examination revealed that the skin and conjunctiva were icteric; abdominal tenderness and palpable liver and spleen were noted. Blood examination revealed anemia (hemoglobin 9.2 g/dL), and liver dysfunction (international normalized ratio, 1.54; total bilirubin, 4.4 mg/dL; alanine aminotransferase, 90 IU/L; y-glutamyltransferase, 159 IU/L). The results of serologic examination for hepatitis B and C virus were negative. An abdominal computed tomography scan showed hepatosplenomegaly. For further investigation, needle biopsy of the liver was performed. On hematoxylin-eosin staining (Figure A), the liver specimen showed slightly distorted lobular architecture. It contained deposits of dark reddish-brown pigment localized in the cytoplasm of the hepatocytes and Kupffer cells in the lumen of the dilated canaliculi and/or interlobular ducts. All the deposits exhibited striking birefringence on polarization microscopic examination (Figure B). Characteristically, some globular deposits appeared bright red and had a centrally-located Maltese cross (arrow). Further, a significant increase was noted in the protoporphyrin levels in the patient's red blood cell count (8578 μg/dL). These findings led to the diagnosis of erythropoietic protoporphyria (EPP). EPP is an inborn error of haem biosynthesis caused by mutations in the gene encoding the mitochondrial enzyme ferrochelatase, which is the final enzyme in the haem biosynthetic pathway. Defects in ferrochelatase lead to an excess of protoporphyrin in the plasma, which in turn induces photosensitivity. Liver damage occurs due to cholestasis caused by excess protoporphyrin and/or exposure to protoporphyrin itself. Protoporphyrin-induced hepatotoxicity is a rare condition occurring in 1%–5% of EPP patients1Anstey A.V. Hift R.J. Liver disease in erythropoietic protoporphyria: insights and implications for management.Gut. 2007; 56: 1009-1018PubMed Google Scholar; however, in patients with deteriorating liver disease, EPP may be irreversible, and such patients require liver transplantation.2McGuire B.M. Bonkovsky H.L. Carithers R.L. et al.Liver transplantation for erythropoietic protoporphyria liver disease.Liver Transpl. 2005; 11: 1590-1596Crossref PubMed Scopus (111) Google Scholar