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Yves Nordmann - One of the best experts on this subject based on the ideXlab platform.
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homozygous variegate Porphyria a severe skin disease of infancy
Clinical Genetics, 2008Co-Authors: Pertti Mustajoki, Yves Nordmann, Raimo Tenhunen, Kirsti Maria Niemi, Helena Kaariainen, Reijo NorioAbstract:A boy exhibited severe bullous skin disease a few days after birth, followed by increased fragility of the exposed skin in spring and summer. Examination at 2 1/2 years of age led to characteristic biochemical findings: increased excretion of fecal porphyrins (coproporphyrin 121 to 131 and protoporphyrin 467 to 576 nmol/g dry weight), and increased erythrocyte protoporphyrin concentration (3643 to 4840 nmol/l). Lymphocyte protoporphyrinogen oxidase activity was very low in the patient (0.4 nmol/mg protein/h) and half-normal (2.7 and 2.3 nmol/mg protein/h) in the parents, suggesting that the patient had homozygous variegate Porphyria. Severe skin symptoms and a high concentration of red cell protoporphyrin concentration in an infant should prompt suspicion of homozygous acute Hepatic Porphyria.
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occurrence of hepatocellular carcinoma in a case of hereditary coproPorphyria
The American Journal of Gastroenterology, 1997Co-Authors: Christophe Andant, Jean-charles Deybach, Jean Claude Soule, Yves NordmannAbstract:: An association between two types of acute Hepatic Porphyria (Porphyria variegata and acute intermittent Porphyria) and hepatocellular carcinoma has previously been reported. In these studies, etiological factors for hepatocellular carcinoma were not completely sought. We report here the first case of an association between hepatocellular carcinoma and hereditary coproPorphyria, the third type of acute Hepatic Porphyria. A 58-yr-old woman with hereditary coproPorphyria presented with a 3.5-cm-diameter hepatocellular carcinoma. Results of exhaustive investigation of etiological factors for hepatocellular carcinoma were negative. Results of microscopic histological analysis of the nontumorous liver were normal. Five years after surgical resection, the patient had no evidence of tumor recurrence.
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Mutations in the Protoporphyrinogen Oxidase Gene in Patients with Variegate Porphyria
Human molecular genetics, 1996Co-Authors: Jean-charles Deybach, Jerome Lamoril, Vasco Da Silva, Bernard Grandchamp, Hervé Puy, Anne-marie Robreau, Yves NordmannAbstract:Variegate Porphyria (VP) is an acute Hepatic Porphyria with autosomal dominant inheritance due to a partial deficiency of protoporphyrinogen oxidase (PPOX) activity. The molecular defect responsible for VP was investigated by sequencing PPOX gene coding sequence from four patients in three unrelated VP families of French Caucasian origin. In a first patient, a point insertion of a G at position 1022 of the cDNA, produced a frameshift resulting in a premature stop codon. In three other patients from two unrelated families we found a missense point mutation leading to glycine to arginine substitution (G232R) in exon 7. This Gly232 appears to be a strictly conserved residue through evolution. In one VP family, we observed the cosegregation of the G232R missense mutation and the deficient PPOX activity. The mutations reported here are the first to be described in patients with VP and support the conclusion that PPOX gene defects are disease causing mutations in human variegate Porphyria.
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a molecular defect in coproporphyrinogen oxidase gene causing harderoPorphyria a variant form of hereditary coproPorphyria
Human Molecular Genetics, 1995Co-Authors: Jerome Lamoril, Vasco Da Silva, Jean-charles Deybach, Bernard Grandchamp, Pavel Martásek, Yves NordmannAbstract:Hereditary coproPorphyria (HC) is an acute Hepatic Porphyria with autosomal dominant inheritance caused by a deficient activity of coproporphyrinogen IX oxidase (CPX). We previously described harderoPorphyria, a homozygous variant form of coproPorphyria in three siblings, characterized by a massive excretion of harderoporphyrin and a marked decrease of coproporphyrinogen IX oxidase activity. In this kindred, the transmission of the disease was autosomal recessive. In the present study, sequencing of cDNA and genomic DNA from these patients revealed a point mutation resulting in a lysine to glutamic acid substitution (K304E) in exon 6 of the gene and the absence of the normal allele, suggesting a homozygous state for the mutation. Expression studies of normal and mutated cDNAs in E.coli demonstrated that this amino acid substitution was responsible for the important decrease in the enzyme activity and for the accumulation of harderoporphyrin. The Michaelis constant of the mutated enzyme was 10-fold higher than normal suggesting that the lysine at position 304 is important for binding the substrate: a slightly increased sensitivity to thermal denaturation was also observed
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acute attacks of Hepatic Porphyria specific treatment with heme arginate
Annales De Medecine Interne, 1993Co-Authors: Yves Nordmann, Jean-charles DeybachAbstract:Les porphyries hepatiques graves (porphyrie aigue intermittente, porphyrie variegata, coproporphyrie) sont des maladies hereditaires liees chacune a un deficit enzymatique specifique intervenant dans la biosynthese de l'heme. Les crises aigues etaient redoutables, tant par l'intensite des douleurs abdominales que par le risque toujours imprevisible des complications neurologiques, pouvant aboutir a une issue fatale ou laisser des sequelles (notamment des paralysies) irreversibles. Depuis 1985, le pronostic des crises aigues a ete completement transforme grâce a l'utilisation de l'heme-arginate. Nous decrivons ici le traitement, par ce produit, de 69 crises aigues de porphyrie correspondant a 30 malades (4 hommes et 26 femmes) entre 1988 et 1991
Kennenth E L Mccoll - One of the best experts on this subject based on the ideXlab platform.
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tin protoporphyrin prolongs the biochemical remission produced by heme arginate in acute Hepatic Porphyria
Gastroenterology, 1993Co-Authors: S B Dover, Ann Graham, Edward J Fitzsimmons, Michael R Moore, Kennenth E L MccollAbstract:Abstract Background: In acute Porphyria, repletion of intraHepatic heme, with exogenously administered heme, suppresses the overproduction of δ-aminolaevulinic acid (ALA) and porphobilinogen (PBG). The effect of reducing heme breakdown has been assessed by administering tin protoporphyrin, a competitive inhibitor of heme oxygenase. Methods: The effect of tin protoporphyrin, 1 μmol/kg, and heme arginate, 3 mg/kg, individually and combined was compared with placebo in patients with an acute porphyric crisis. The treatments were given by intravenous infusion on three successive mornings. Thirty-four attacks were studied in 8 patients (9 placebo, 10 heme arginate alone, 4 tin protoporphyrin alone, and 11 combination treatments). Results: Placebo and tin protoporphyrin alone had little effect on ALA and PBG excretion. Following heme arginate alone or combined with tin protoporphyrin, there was a marked and similar suppression of both ALA and PBG excretion ( P P P Conclusions: These findings suggest that inhibition of heme oxygenase by tin protoporphyrin prolongs the biochemical remission induced by heme arginate in the porphyric crisis.
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tin protoporphyrin prolongs the biochemical remission produced by heme arginate in acute Hepatic Porphyria
Gastroenterology, 1993Co-Authors: S B Dover, Ann Graham, Edward J Fitzsimmons, Michael R Moore, Kennenth E L MccollAbstract:Background: In acute Porphyria, repletion of intraHepatic heme, with exogenously administered heme, suppresses the overproduction of δ-aminolaevulinic acid (ALA) and porphobilinogen (PBG). The effect of reducing heme breakdown has been assessed by administering tin protoporphyrin, a competitive inhibitor of heme oxygenase. Methods: The effect of tin protoporphyrin, 1 μmol/kg, and heme arginate, 3 mg/kg, individually and combined was compared with placebo in patients with an acute porphyric crisis. The treatments were given by intravenous infusion on three successive mornings. Thirty-four attacks were studied in 8 patients (9 placebo, 10 heme arginate alone, 4 tin protoporphyrin alone, and 11 combination treatments). Results: Placebo and tin protoporphyrin alone had little effect on ALA and PBG excretion. Following heme arginate alone or combined with tin protoporphyrin, there was a marked and similar suppression of both ALA and PBG excretion (P < 0.005 for each, compared with pretreatment values). However, on the 5th day after discontinuing treatment, the excretion of ALA and PBG were both lower following combination therapy than following heme arginate alone (P < 0.005 and P < 0.01, respectively). Conclusions: These findings suggest that inhibition of heme oxygenase by tin protoporphyrin prolongs the biochemical remission induced by heme arginate in the porphyric crisis.
S B Dover - One of the best experts on this subject based on the ideXlab platform.
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lofepramine a safe anti depressant in acute Hepatic Porphyria
Journal of Psychopharmacology, 1994Co-Authors: S B Dover, Ann Graham, Michael R Moore, Kenneth E L MccollAbstract:The acute Porphyrias are a group of neuropsychiatric disorders in which a life-threatening crisis can be precipitated by a variety of drugs, including antidepressants. Because of the need to find an antidepressant that is safe for Porphyria patients, we have studied the effects of lofepramine on Porphyria in laboratory rats and Porphyria patients. The rats did not exhibit a significant rise in Hepatic δ-aminolaevulinic acid synthase activity (a marker of drug porphyrinogenicity) when given the drug compared with its solvent alone. Four Porphyria patients exhibited no clinical evidence of disease activation after exposure to the drug. The biochemical activity of their disease was assessed by measurement of the 24-h urinary excretion of δ- aminolaevulinic acid and porphobilinogen (haem precursors formed prior to the metabolic block). No patient exhibited a sustained rise compared to pre-treatment levels, or between low dose and high dose lofepramine. We suggest that lofepramine is probably safe in acute por...
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tin protoporphyrin prolongs the biochemical remission produced by heme arginate in acute Hepatic Porphyria
Gastroenterology, 1993Co-Authors: S B Dover, Ann Graham, Edward J Fitzsimmons, Michael R Moore, Kennenth E L MccollAbstract:Abstract Background: In acute Porphyria, repletion of intraHepatic heme, with exogenously administered heme, suppresses the overproduction of δ-aminolaevulinic acid (ALA) and porphobilinogen (PBG). The effect of reducing heme breakdown has been assessed by administering tin protoporphyrin, a competitive inhibitor of heme oxygenase. Methods: The effect of tin protoporphyrin, 1 μmol/kg, and heme arginate, 3 mg/kg, individually and combined was compared with placebo in patients with an acute porphyric crisis. The treatments were given by intravenous infusion on three successive mornings. Thirty-four attacks were studied in 8 patients (9 placebo, 10 heme arginate alone, 4 tin protoporphyrin alone, and 11 combination treatments). Results: Placebo and tin protoporphyrin alone had little effect on ALA and PBG excretion. Following heme arginate alone or combined with tin protoporphyrin, there was a marked and similar suppression of both ALA and PBG excretion ( P P P Conclusions: These findings suggest that inhibition of heme oxygenase by tin protoporphyrin prolongs the biochemical remission induced by heme arginate in the porphyric crisis.
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tin protoporphyrin prolongs the biochemical remission produced by heme arginate in acute Hepatic Porphyria
Gastroenterology, 1993Co-Authors: S B Dover, Ann Graham, Edward J Fitzsimmons, Michael R Moore, Kennenth E L MccollAbstract:Background: In acute Porphyria, repletion of intraHepatic heme, with exogenously administered heme, suppresses the overproduction of δ-aminolaevulinic acid (ALA) and porphobilinogen (PBG). The effect of reducing heme breakdown has been assessed by administering tin protoporphyrin, a competitive inhibitor of heme oxygenase. Methods: The effect of tin protoporphyrin, 1 μmol/kg, and heme arginate, 3 mg/kg, individually and combined was compared with placebo in patients with an acute porphyric crisis. The treatments were given by intravenous infusion on three successive mornings. Thirty-four attacks were studied in 8 patients (9 placebo, 10 heme arginate alone, 4 tin protoporphyrin alone, and 11 combination treatments). Results: Placebo and tin protoporphyrin alone had little effect on ALA and PBG excretion. Following heme arginate alone or combined with tin protoporphyrin, there was a marked and similar suppression of both ALA and PBG excretion (P < 0.005 for each, compared with pretreatment values). However, on the 5th day after discontinuing treatment, the excretion of ALA and PBG were both lower following combination therapy than following heme arginate alone (P < 0.005 and P < 0.01, respectively). Conclusions: These findings suggest that inhibition of heme oxygenase by tin protoporphyrin prolongs the biochemical remission induced by heme arginate in the porphyric crisis.
Robert J Desnick - One of the best experts on this subject based on the ideXlab platform.
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explore a prospective multinational natural history study of patients with acute Hepatic Porphyria with recurrent attacks
Hepatology, 2020Co-Authors: Laurent Gouya, Manisha Balwani, John D Phillips, Montgomery D Bissell, Paolo Ventura, David C Rees, Ulrich Stolzel, Raili Kauppinen, Janneke G Langendonk, Robert J DesnickAbstract:textabstractBackground and Aims: Acute Hepatic Porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. Approach and Results: EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute Hepatic Porphyria who experience recurrent attacks. Eligible patients had a confirmed acute Hepatic Porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of Hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization. Conclusions: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies.
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EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks
'Wiley', 2020Co-Authors: Gouya L., Balwani M., Ventura P., Kauppinen R., Janneke G Langendonk, D.m. Bissell, J.d. Phillips, Dc Rees, Robert J DesnickAbstract:BACKGROUND AND AIMS: Acute Hepatic Porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. APPROACH AND RESULTS: EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute Hepatic Porphyria who experience recurrent attacks. Eligible patients had a confirmed acute Hepatic Porphyria diagnosis and had experienced 653 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of Hepatic \u3b4-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, \u3b4-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization. CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies
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EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks
'Wiley', 2019Co-Authors: Laurent Gouya, Paolo Ventura, David C Rees, Ulrich Stolzel, Raili Kauppinen, Janneke G Langendonk, M. Balwani, D.m. Bissell, J.d. Phillips, Robert J DesnickAbstract:Background and Aims Acute Hepatic Porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. Approach and Results EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute Hepatic Porphyria who experience recurrent attacks. Eligible patients had a confirmed acute Hepatic Porphyria diagnosis and had experienced >= 3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of Hepatic delta-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, delta-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization. Conclusions Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies
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experiences and concerns of patients with recurrent attacks of acute Hepatic Porphyria a qualitative study
Molecular Genetics and Metabolism, 2016Co-Authors: Hetanshi Naik, Manisha Balwani, Mikayla Stoecker, Saskia C Sanderson, Robert J DesnickAbstract:Abstract Background The acute Hepatic Porphyrias (AHPs) are rare inborn errors of heme biosynthesis, characterized clinically by life-threatening acute neurovisceral attacks. Patients with recurrent attacks have a decreased quality of life (QoL); however, no interactive assessment of these patients' views has been reported. We conducted guided discussions regarding specific topics, to explore patients' disease experience and its impact on their lives. Methods Sixteen AHP patients experiencing acute attacks were recruited to moderator-led online focus groups. Five groups (3–4 patients each) were conducted and thematic analyses to identify, examine, and categorize patterns in the data was performed. Results All patients identified prodromal symptoms that began days prior to acute severe pain; the most common included confusion (“brain fog"), irritability, and fatigue. Patients avoided hospitalization due to prior poor experiences with physician knowledge of AHPs or their treatment. All patients used complementary and alternative medicine treatments to avoid hospitalization or manage chronic pain and 81% reported varying degrees of effectiveness. All patients indicated their disease impacted personal relationships due to feelings of isolation and difficulty adjusting to the disease's limitations. Conclusion Patients with recurrent attacks recognize prodromal warning symptoms, attempt to avoid hospitalization, turn to alternative treatments, and have markedly impaired QoL. Counseling and individualized support is crucial for AHP patients with recurrent attacks.
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diagnosis of feline acute intermittent Porphyria presenting with erythrodontia requires molecular analyses
Veterinary Journal, 2013Co-Authors: Sonia Clavero, Yuri Ahuja, David F Bishop, Brittany Kwait, Mark E Haskins, Urs Giger, Robert J DesnickAbstract:Erythrodontia is the hallmark of human congenital erythropoietic Porphyria (CEP), but is also a major phenotypic feature of acute intermittent Porphyria (AIP) in cats. In this study, detailed biochemical and molecular analyses were performed on two unrelated cats with autosomal dominant AIP that presented with erythrodontia, yellow-brown urine and mild changes in erythrocytes. The cats had elevated concentrations of urinary 5-aminolevulinic acid and porphobilinogen, and half normal erythrocytic hydroxymethylbilane synthase (HMBS) activity. Two novel HMBS mutations were detected; one cat had a deletion (c.107_110delACAG) and one cat had a splicing alteration (c.826-1G>A), both leading to premature stop codons and truncated proteins (p.D36Vfs 6 and p.L276Efs 6, respectively). These studies highlight the importance of appropriate biochemical and molecular genetic analyses for the accurate diagnoses of Porphyrias in cats and extend the molecular genetic heterogeneity of feline AIP. Thus, although erythrodontia is a classic sign of congenital erythropoietic Porphyria in human beings, cats with erythrodontia may have acute intermittent Porphyria, a Hepatic Porphyria.
Ann Graham - One of the best experts on this subject based on the ideXlab platform.
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lofepramine a safe anti depressant in acute Hepatic Porphyria
Journal of Psychopharmacology, 1994Co-Authors: S B Dover, Ann Graham, Michael R Moore, Kenneth E L MccollAbstract:The acute Porphyrias are a group of neuropsychiatric disorders in which a life-threatening crisis can be precipitated by a variety of drugs, including antidepressants. Because of the need to find an antidepressant that is safe for Porphyria patients, we have studied the effects of lofepramine on Porphyria in laboratory rats and Porphyria patients. The rats did not exhibit a significant rise in Hepatic δ-aminolaevulinic acid synthase activity (a marker of drug porphyrinogenicity) when given the drug compared with its solvent alone. Four Porphyria patients exhibited no clinical evidence of disease activation after exposure to the drug. The biochemical activity of their disease was assessed by measurement of the 24-h urinary excretion of δ- aminolaevulinic acid and porphobilinogen (haem precursors formed prior to the metabolic block). No patient exhibited a sustained rise compared to pre-treatment levels, or between low dose and high dose lofepramine. We suggest that lofepramine is probably safe in acute por...
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tin protoporphyrin prolongs the biochemical remission produced by heme arginate in acute Hepatic Porphyria
Gastroenterology, 1993Co-Authors: S B Dover, Ann Graham, Edward J Fitzsimmons, Michael R Moore, Kennenth E L MccollAbstract:Abstract Background: In acute Porphyria, repletion of intraHepatic heme, with exogenously administered heme, suppresses the overproduction of δ-aminolaevulinic acid (ALA) and porphobilinogen (PBG). The effect of reducing heme breakdown has been assessed by administering tin protoporphyrin, a competitive inhibitor of heme oxygenase. Methods: The effect of tin protoporphyrin, 1 μmol/kg, and heme arginate, 3 mg/kg, individually and combined was compared with placebo in patients with an acute porphyric crisis. The treatments were given by intravenous infusion on three successive mornings. Thirty-four attacks were studied in 8 patients (9 placebo, 10 heme arginate alone, 4 tin protoporphyrin alone, and 11 combination treatments). Results: Placebo and tin protoporphyrin alone had little effect on ALA and PBG excretion. Following heme arginate alone or combined with tin protoporphyrin, there was a marked and similar suppression of both ALA and PBG excretion ( P P P Conclusions: These findings suggest that inhibition of heme oxygenase by tin protoporphyrin prolongs the biochemical remission induced by heme arginate in the porphyric crisis.
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tin protoporphyrin prolongs the biochemical remission produced by heme arginate in acute Hepatic Porphyria
Gastroenterology, 1993Co-Authors: S B Dover, Ann Graham, Edward J Fitzsimmons, Michael R Moore, Kennenth E L MccollAbstract:Background: In acute Porphyria, repletion of intraHepatic heme, with exogenously administered heme, suppresses the overproduction of δ-aminolaevulinic acid (ALA) and porphobilinogen (PBG). The effect of reducing heme breakdown has been assessed by administering tin protoporphyrin, a competitive inhibitor of heme oxygenase. Methods: The effect of tin protoporphyrin, 1 μmol/kg, and heme arginate, 3 mg/kg, individually and combined was compared with placebo in patients with an acute porphyric crisis. The treatments were given by intravenous infusion on three successive mornings. Thirty-four attacks were studied in 8 patients (9 placebo, 10 heme arginate alone, 4 tin protoporphyrin alone, and 11 combination treatments). Results: Placebo and tin protoporphyrin alone had little effect on ALA and PBG excretion. Following heme arginate alone or combined with tin protoporphyrin, there was a marked and similar suppression of both ALA and PBG excretion (P < 0.005 for each, compared with pretreatment values). However, on the 5th day after discontinuing treatment, the excretion of ALA and PBG were both lower following combination therapy than following heme arginate alone (P < 0.005 and P < 0.01, respectively). Conclusions: These findings suggest that inhibition of heme oxygenase by tin protoporphyrin prolongs the biochemical remission induced by heme arginate in the porphyric crisis.