Liver transplantation for acute-on-chronic liver failure from erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is an inherited disorder of the heme metabolic pathway that is characterized by accumulation of protoporphyrin in the blood, erythrocytes, and tissues, and cutaneous manifestations of photosensitivity, all resulting from abnormalities in ferrochelatase (FECH) activity due to mutations in the FECH gene. Protoporphyrin is excreted by the liver, and excess protoporphyrin leads to cholelithiasis with obstructive episodes and chronic liver disease, finally progressing to liver cirrhosis. Patients with end-stage EPP-associated liver disease require liver transplantation. We describe here a 31-year-old male patient with EPP who experienced acute-on-chronic liver failure and underwent deceased-donor liver transplantation. Surgical and postoperative care included specific shielding from exposure to ultraviolet radiation to prevent photosensitivity-associated adverse effects. The patient recovered uneventfully and was doing well 24 months after transplantation. Future prevention and treatment of liver disease are discussed in detail.

Cholestyramine resin for erythropoietic protoporphyria with severe hepatic disease: a case report / 대한간학회지

Erythropoietic protoporphyria (EPP) is a rare disorder of heme biosynthesis caused by mutations in the gene encoding the enzyme ferrochelatase. In EPP, deficient ferrochelatase activity leads to the excessive production and biliary excretion of protoporphyrin (PP). The major clinical features of EPP are photosensitivity and hepatobiliary disease that may progress to severe liver disease, that are caused by the toxicity of PP. EPP-related liver disease has been treated medically or surgically including liver transplantation. We described a 20-year-old male with severe liver disease who was diagnosed with EPP based on clinical and laboratory findings. He was treated with cholestyramine resin. Six months after the treatment, he was doing well without any abdominal pain or photosensitivity.

Effect of treadmill exercise and nutrition supplement on activity and gene expression of rate-limiting enzyme of heme metabolism and globin / 中国应用生理学杂志

<p><b>AIM</b>To investigate the possible role of rate-limiting enzyme of heme metabolism and globin in the development of the low hemoglobin (Hb), red blood (cell) count (RBC) and hematocrit (Hct) after long-term exercise, and effect of nutrition supplement on sports anemia.</p><p><b>METHODS</b>Male Wistar rats were randomly assigned to three groups (n = 10): control (C), exercise (P) and exercise + nutrition (G). Animals in the P and G groups started treadmill running at 30 m/min, 0% grade, 1 min/time. Running time was gradually increased with 2 min/time during initial 5 weeks and final 4 weeks. In addition, running frequency was 2 times/day except initial 2 weeks. At the end of eleventh week, gene expression of 5-aminolevulinate synthase (ALAS), ferrochelatase, alpha-globin and beta-globin in bone marrow were measured with RT-PCR. Mean-while heme oxygenase 1 (HO-1) activity in liver was measured with immunohistochemical method.</p><p><b>RESULTS</b>Eleven weeks of exercise induced a significant increase in HO-1 and a significant increase in gene expression of beta-globin (P < 0.01, P < 0.05, respectively). Treatment with anti-sports anemia compound dosage led to no significant differences in rate-limiting enzyme of heme metabolism and globin in the exercised rats. The G group had a significantly higher HO-1 level in liver than the C group (P < 0.01). These finds showed that exercise was associated with no significant difference in heme synthetase and alpha-globin gene expression, and significant difference in heme catabolic enzyme and beta-globin gene expression.</p><p><b>CONCLUSION</b>The increase of HO-1 activity in liver might be one of the causes of the lower Hb, RBC and Hct status in exercised rats.</p>

Heme metabolism enzymes are dynamically expressed during Xenopus embryonic development

As the key component of many hemoproteins (heme-containing proteins), heme is involved in a broad range of biological processes. Enzymes required for heme biosynthesis and degradation pathways are evolutionarily conserved. While heme metabolism has been studied extensively, the expression of heme metabolism enzymes during development has not been described. Here, we report that all heme biosynthases and two heme oxygenases, which initiate heme degradation, are dynamically expressed during Xenopus embryonic development. All heme synthases, with the exception of aminolevulinic acid synthase 2, are maternally expressed. At neurula stage, heme synthases are expressed in the developing neural tissue and in migrating neural crest cells. At the swimming tadpole stage, expression of heme synthases can be detected in multiple lineages, including eyes, neural crest cells, developing central nervous system, ventral blood island, pronephron, and pronephric tubule. Similar to heme synthases, heme oxygenases are expressed maternally. Zygotic expression of heme oxygenases is mainly restricted to the developing neural and neural crest lineages. Unlike heme synthases, heme oxygenases are not expressed in the ventral blood island and are expressed at a very low level in the pronephron and pronephric tubule. This indicates that heme metabolism may play important roles during development.

Porfiria aguda: reporte de caso y revisión de tema / Porfiria aguda. reporte de caso e revisão de tema / Acute porphyria: case report and review

Las porfirias agudas comprenden un grupo de desórdenes genéticos en la síntesis del grupo heme que pueden comprometer la vida del paciente y cuyas manifestaciones son similares a las de otras condiciones médicas. La falta de reconocimiento clínico y la demora en el diagnóstico retarda en ocasiones el inicio del tratamiento específico, incrementando así la morbimortalidad. El diagnóstico se puede confirmar rápidamente demostrando niveles elevados de porfirinas totales en sangre y en orina y de porfobilinógeno y de ácido delta-aminolevulínico en la orina. La terapia con hemina intravenosa iniciada tan pronto como sea posible es el tratamiento más efectivo y los factores desencadenantes se deben identificar y minimizar al máximo. Un diagnóstico temprano y un completo y adecuado tratamiento mejoran el pronóstico y previenen el desarrollo de complicaciones. En este reporte de caso se muestran las manifestaciones clínicas típicas de una porfiria aguda en una mujer joven a la que se le hizo un rápido diagnóstico, pero que falleció sin recibir tratamiento por la falta de disponibilidad del medicamento en el país...

The acute porphyries include a group of genetic disorders in the heme biosynthesis, that cause neurovisceral manifestations that mimic many medical conditions, psychiatric illnesses and sometimes, it even compromises the patients life. The lack of clinical recognition and delay in diagnosis, often retard the specific treatment and follow an increase in the morbimortality. The diagnosis can be quickly confirmed when demonstrating levels markedly high of porphobylinogen, and delta-aminolevulínic acid in urine and total porphyirines in blood and urine. The therapy with intravenous Hemine started as soon as possible is the most effective treatment. The trigger factors should be identified and minimized. An early diagnosis and appropriate treatment thoroughly improves its prognosis and prevents the development of further complications. In this case report we show the typical manifestations of acute porphyria in a young woman, in which case the diagnosis was not delayed, the problem was the attainment of the specific treatment which was not available in Colombia and the patient died without treatment...

As porfiarias agudas compreendem um grupo de desordens genéticas na síntese do grupo heme que podem comprometer a vida do paciente e cujas manifestações são similares às de outras condições médicas. A falta de reconhecimento clínico e a demora no diagnóstico retarda em ocasiões o início do tratamento específico, incrementando assim a morbi mortalidade. O diagnostico se pode confirmar rapidamente demonstrando níveis elevados de porfirinas totais em sangue e na urina e de porfobilinógeno e de ácido aminolevulínico na urina. A terapia com hemina intravenosa iniciada tão cedo como seja possível é o tratamento mais efetivo e os fatores desencadeantes se devem identificar e minimizar ao máximo. Um diagnóstico cedo e um completo e adequado tratamento melhoram o prognóstico e prevem o desenvolvimento de complicações. Neste reporte de caso mostram-se as manifestações clínicas típicas de uma porfiria aguda numa mulher jovem à que se lhe fez um rápido diagnóstico, mas que faleceu sem receber tratamento pela falta de disponibilidade do medicamento no país...

A Case of Erythropoietic Protoporphyria with Severe Liver Dysfunction and Neurological Symptoms / 대한소아소화기영양학회지

Erythropoietic protoporphyria is a genetic disorder due to a deficiency of ferrochelatase resulting in excessive accumulation and excretion of protoporphyrin. The predominant clinical feature is photosensitivity. Severe hepatic failure occurs in a small percentage of patients, and neurological symptoms are very rare. We report a case of erythropoietic protoporphyria associated with severe hepatic dysfunction and neurological symptoms. A 9-year-old girl presented with severe abdominal pain, nausea, weakness and pain of extremities, and urinary retention. Ultrasonogram and abdominal CT scanning revealed a diffuse infiltrated and enlarged liver. Liver biopsy showed deposition of dense dark brown pigment within the bile, hepatocytes and Kupffer cells. Plus, dense dark brown deposits gave a red birefringent under polarize light. Porphyrin studies demonstrated markedly elevated serum free erythrocyte protoporphyrin. This girl was diagnosed as erythropoietic protoporphyria with severe liver dysfunction and neurological symptoms.

The decrease in uroporphyrinogen decarboxylase activity induced by ethanol predisposes rats to the development of porphyria and accelerates xenobiotic-triggered porphyria, regardless of hepatic damage

We evaluated the porphyrinogenic ability of ethanol (20 percent in drinking water) per se, its effect on the development of sporadic porphyria cutanea tarda induced by hexachlorobenzene in female Wistar rats (170-190 g, N = 8/group), and the relationship with hepatic damage. Twenty-five percent of the animals receiving ethanol increased up to 14-, 25-, and 4.5-fold the urinary excretion of delta-aminolevulinate, porphobilinogen, and porphyrins, respectively. Ethanol exacerbated the precursor excretions elicited by hexachlorobenzene. Hepatic porphyrin levels increased by hexachlorobenzene treatment, while this parameter only increased (up to 90-fold) in some of the animals that received ethanol alone. Ethanol reduced the activities of uroporphyrinogen decarboxylase, delta-aminolevulinate dehydrase and ferrochelatase. In the ethanol group, many of the animals showed a 30 percent decrease in uroporphyrinogen activity; in the ethanol + hexachlorobenzene group, this decrease occurred before the one caused by hexachlorobenzene alone. Ethanol exacerbated the effects of hexachlorobenzene, among others, on the rate-limiting enzyme delta-aminolevulinate synthetase. The plasma activities of enzymes that are markers of hepatic damage were similar in all drug-treated groups. These results indicate that 1) ethanol exacerbates the biochemical manifestation of sporadic hexachlorobenzene-induced porphyria cutanea tarda; 2) ethanol per se affects several enzymatic and excretion parameters of the heme metabolic pathway; 3) since not all the animals were affected to the same extent, ethanol seems to be a porphyrinogenic agent only when there is a predisposition, and 4) hepatic damage showed no correlation with the development of porphyria cutanea tarda

A Case of Erythropoietic Protoporphyria Screened by RBC Fluorescence Microscopy / 대한피부과학회지

Erythropoietic protoporphyria (EPP), caused by decreased activity of the enzyme ferrochelatase, is characterized clinically by burning photosensitivity beginning from childhood, and chemically by excessive amounts of red blood cell protoporphyrins. 1-10% of EPP patients develop potentially fatal protoporphyric hepatic failure. The diagnosis of EPP had been missed in many cases when traditional solvent extraction qualitative screening test was used for blood porphyrins, and use of fluorescence microscopy improved this problem. We report a case of EPP screened by fluorescence microscopy of erythrocytes in a 50-year-old man complaining of photosensitivity. We recommend fluorescence microscopy could be the screening test of choice for the detection of increased red blood cell porphyrins.

A Case of Erythropoietic Protoporphyria / 대한피부과학회지

Erythropoietic protoporphyria(EPP) is an inherited inborn error of porphyrin metabolism caused by decreased activity of the enzyme ferrochelatase. EPP is characterized clinically by photosensitivity to visible light commencing in childhood, and biochemically by elevated red cell free protoporphyrin levels. We report herein a case of EPP which occurred in a 44-year-old man and his family. He had suffered from immediate photosensitivity since he was 4 years old. He was presented with burning, erythema, scars and waxy thickening of the sun-exposed skin. Red cell free protoporphyrin level was elevated and urinary porphyrins were normal. Histopathologically, homogeneous eosinophilic materials that stained with PAS were deposited in perivascular area of upper dermis. He was managed with light restriction and sunscreen.

Erythropoietic Protoporphyria in a Family

Erythropoietic protoporphyria (EPP) is an autosomal dominant condition due to decreased activity of ferrochelatase. The disease is characterized by a wide range of photocutaneous changes and occasionally by liver disease. The level of protoporphyin is raised in erythkocytes and it may also be increased in the feces. We report herein a case of EPP present in a family which was diagnosed by a high free erythrocyte protoporphyrin (FEP) count.

Erythropoietic Protoporphyria in a Family

Erythropoietic protoporphyria (EPP) is an autosomal dominant condition due to decreased activity of ferrochelatase. The disease is characterized by a wide range of photocutaneous changes and occasionally by liver disease. The level of protoporphyin is raised in erythkocytes and it may also be increased in the feces. We report herein a case of EPP present in a family which was diagnosed by a high free erythrocyte protoporphyrin (FEP) count.