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Manfred O. Doss - One of the best experts on this subject based on the ideXlab platform.

  • Porphyrien
    Der Internist, 2010
    Co-Authors: Ulrich Stölzel, Thomas Stauch, Manfred O. Doss
    Abstract:

    Porphyrien sind Stoffwechselerkrankungen, denen eine Störung der Hämbiosynthese zugrunde liegt. Klinisch wird zwischen akuten und nicht-akuten Porphyrien differenziert. Bei symptomatischen akuten hepatischen Porphyrien werden vermehrt Porphyrinvorläufer, denen neurotoxische Eigenschaften zugeschrieben werden, und Porphyrine synthetisiert. In diese Gruppe gehören die akute intermittierende Porphyrie, die Porphyria variegata, die hereditäre Koproporphyrie und die Doss-Porphyrie. Klinisch entwickelt sich ein akutes Syndrom mit abdominellen, psychiatrischen, neurologischen und kardiovaskulären Symptomen. Eine mehr als 10-fache Erhöhung von Porphobilinogen oberhalb der Norm im Spontanurin ist (außer bei Doss-Porphyrie) für die Diagnose ausschlaggebend. Neben der symptomatischen Therapie mit nicht porphyrinogenen Medikamenten, Elektrolytausgleich und intensiver Überwachung sind Glukose und Hämarginat intravenös zur Behandlung etabliert. Bei den nicht-akuten Formen – Porphyria cutanea tarda, erythropoetische und X-chromosomal-dominante Protoporphyrie sowie kongenitale erythropoetische Porphyrie – führen akkumulierte Porphyrine zur Lichtempfindlichkeit der Haut (Photodermatose) und schweren Leberschäden. Der jeweilige Enzymdefekt prägt aufgrund seiner Position in der Hämbiosynthesekette das diagnostisch wegweisende Muster akkumulierter Porphyrine. Sämtliche nicht-akuten Porphyrien erzwingen die Notwendigkeit eines effektiven Lichtschutzes der exponierten Hautareale. Daneben gibt es, je nach Störung, weitere spezifische Therapieoptionen. Eine definitive Heilmethode stellt bei den therapierefraktären akuten hepatischen Porphyrien als ultima ratio die Lebertransplantation dar, während schwere Verlaufsformen der erythropoetischen Porphyrien durch eine allogene Knochenmarkstransplantation geheilt werden können. Porphyrias are metabolic disorders of the heme biosynthesis. Clinically, they can be differentiated into acute and non-acute Porphyrias. The symptomatic phase of acute hepatic Porphyrias is characterized by overproduction of neurotoxic porphyrin precursors and porphyrins. Acute intermittent Porphyria, Variegate Porphyria, Hereditary coproPorphyria and Doss Porphyria belong to this group of metabolic disorders. The clinical presentation of the acute hepatic Porphyria syndrome includes abdominal, psychiatric, neurological and cardiovascular symptoms. The diagnosis is based on a tenfold increased urinary excretion of porphobilinogen (apart from Doss Porphyria). Besides symptomatic therapy with non-porphyrinogenic drugs, electrolyte compensation and intensive monitoring, intravenous administration of glucose and heme arginate is established for treatment. Among the non-acute types like Porphyria cutanea tarda, Erythropoietic protoPorphyria and Congenital erythropoietic Porphyria, the accumulated porphyrins cause photosensitivity of the skin up to severe liver damage. The location of the deficient enzyme within the heme biosynthesic pathway determines the pattern of the accumulated porphyrins. Besides light protection, there are different therapies depending on the type of non-acute Porphyria. Ultimately, liver transplantation may be considered in therapy-resistant cases of acute hepatic Porphyrias and bone marrow transplantation in severe cases of erythropoietic Porphyrias.

  • Studies on coproporphyrin isomers in urine and feces in the Porphyrias.
    Clinica Chimica Acta, 1999
    Co-Authors: A Kühnel, U Gross, K Jacob, Manfred O. Doss
    Abstract:

    Abstract The urinary and fecal distribution and the relative proportions of the four coproporphyrin (copro) isomers I–IV were analysed in 20 healthy subjects and in patients suffering from one of the seven common types of hepatic or erythropoietic hereditary Porphyrias. The ratios of copro isomers I–IV were analyzed by ion-pair high-performance liquid chromatography (HPLC). Observations showed significantly increased proportions of fecal copro isomer I and decreased proportions of copro isomers III, II and IV in erythropoietic Porphyrias. In acute hepatic Porphyrias the excretion of fecal copro isomer III is dominant (isomer III=58.4±24.0%; x ±S.D.) and significantly higher (P x ±S.D.) and chronic hepatic Porphyrias (isomer III=25.8±7.6%; x ±S.D.). The increased proportions of fecal copro isomer III proved to be important for the diagnosis of hereditary coproPorphyria and Porphyria variegata independent of the clinical phase existing. These last two acute hepatic Porphyrias also showed markedly elevated percentages of the fecal atypical isomers II and IV. In urine significantly decreased proportions of copro isomer I in acute hepatic Porphyrias (isomer I=12.3±6.0%; x ±S.D.) could be observed as compared with non-acute Porphyrias (isomer I=53.7±15.2%; x ±S.D.). Conversely, the proportion of urinary copro isomer III was significantly higher in acute hepatic Porphyrias (isomer III=81.4±6.4%; x ±S.D.). As expected, the greatest amounts of urinary copro isomer I were found in congenital erythropoietic Porphyria (isomer I=92.0±3.3; x ±S.D.) and protoPorphyria with hepatobiliary complications (isomer I=81.3±10.7; x ±S.D.). The atypical urinary copro isomers II and IV were detected in all types of Porphyrias ranging from 0.1 to 11.5%. The combined amounts of copro isomers II and IV show a significantly decreased percentage in congenital erythropoietic Porphyria as compared with all other types of hereditary Porphyrias. In conclusion, we demonstrate that the characteristic pattern of the copro isomer constellations I–IV in the various types of Porphyrias are of differential diagnostic importance. The inversion of the I to III ratio in feces in hereditary coproPorphyria and Porphyria variegata allows the recognition of gene carriers.

  • Dual Porphyria of Coexisting variegata and Cutanea Tarda
    European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies, 1995
    Co-Authors: Ina Sieg, Lalit K. Bhutani, Manfred O. Doss
    Abstract:

    While Porphyria cutanea tarda and Porphyria variegata are independent diseases, we report on seven rare cases with a coincidence of these two different Porphyrias in one individuum. The mutual clinical symptom was a cutaneous photosensitivity, which is a major symptom in Porphyria cutanea tarda and a facultative one in Porphyria variegata. Additionally, five patients had also experienced episodes of acute abdominal pain, which were in three cases accompanied by neurological symptoms, thus offering evidence for an acute hepatic Porphyria, such as Porphyria variegata. Determination of urinary porphyrin metabolites revealed a Porphyria cutanea tarda-like excretion pattern with an elevation of uroporphyrin (mean 1134 nmol/24h, range 563-4052, normal ≤ 30) and heptacarboxyporphyrin (mean 389 nmol/24 h, range 64-830, normal ≤ 4). In all patients, however, urinary coproporphyrin was also increased, reaching levels too high for Porphyria cutanea tarda but typical for Porphyria variegata (mean 1788 nmol/24 h, range 142-4168, normal ≤ 120). Fecal porphyrin excretion also resembled the variegate-type with a high concentration especially of protoporphyrin (mean 628 nmol/g dry weight, range 401-1018, normal ≤ 151), accompanied by an increase of coproporphyrin (mean 194 nmol/g dry weight, range 75-409, normal ≤ 37). The urinary porphyrin precursors 5-aminolaevulinic acid and porphobilinogen were markedly elevated only in one patient, who was in an acute porphyric phase at the time of investigation. The activity of uroporphyrinogen decarboxylase in erythrocytes was considerably decreased in six of our cases (33-64%) and slightly diminished in the other one (83% of normal activity). Those metabolic excretion profiles, supplemented by the cutanea tarda-associated uroporphyrinogen decarboxylase deficiency, reflect an intermediate pattern with characteristics of both Porphyria cutanea tarda and variegata, as was confirmed by comparison with 15 cases of Porphyria variegata and 10 cases of Porphyria cutanea tarda.

  • Dual Porphyria of Coexisting variegata and Cutanea Tarda1'2)
    1995
    Co-Authors: Eur J Clin, Lalit K. Bhutani, Ina Sieg, Cheni Clin Biochem, Manfred O. Doss
    Abstract:

    Summary: While Porphyria cutanea tarda and Porphyria variegata are independent diseases, we report on seven rare cases with a coincidence of these two different Porphyrias in one Individuum. The mutual clinical symptom was a cutaneous photosensitivity, which is a major symptom in Porphyria cutanea tarda and a facultative one in Porphyria variegata. Additionally, five patients had also experienced episodes of acute abdominal pain, which were in three cases accompanied by neurological symptoms, thus offering evidence for an acute hepatic Porphyria, such as Porphyria variegata. Determination of urinary porphyrin metabolites revealed a Porphyria cutanea tarda-like excretion pattern with an elevation of uroporphyrin (mean 1134 nmol/24h, range 563—4052, normal < 30) and heptacarboxyporphyrin (mean 389 nmol/24h, range 64—830, normal ^4). In all patients, however, urinary coproporphyrin was also increased, reaching levels too high for Porphyria cutanea tarda but typical for Porphyria variegata (mean 1788 nmol/ 24 h, range 142—4168, normal ^ 120). Fecal porphyrin excretion also resembled the variegate-type with a high concentration especially of protoporphyrin (mean 628 nmol/g dry weight, range 401 — 1018, normal ̂ 151), accom-panied by an increase of coproporphyrin (mean 194 nmol/g dry weight, range 75—409, normal < 37). The urinary porphyrin precursors 5-aminolaevulinic acid and porphobilinogen were markedly elevated only in one patient, who was in an acute porphyric phase at the time of investigation. The activity of uroporphyrinogen decarboxylase i

Y. Nordmann - One of the best experts on this subject based on the ideXlab platform.

  • A case of association between hepatocellular carcinoma and Porphyria variegata.
    Scandinavian journal of gastroenterology, 1994
    Co-Authors: J. Germanaud, F. Luthier, X. Causse, R. Kerdraon, D. Grossetti, D. Gargot, Y. Nordmann
    Abstract:

    Germanaud J, Luthier F, Causse X, Kerdraon R, Grossetti D, Gargot D, Nordmann Y. A case of association between hepatocellular carcinoma and Porphyria variegata. Scand J Gastroenterol 1994;29:671-672Background: A correlation between acute intermittent Porphyria or Porphyria cutanea tarda and hepatocellular carcinoma (HCC) has been noted in several studies, but only one case of association between HCC and Porphyria variegata has been reported. We therefore report another case of association between HCC and Porphyria variegata.Methods: A 54-year-old nurse with familial Porphyria variegata who developed an HCC was studied. The diagnosis of Porphyria variegata was made in the course of a familial survey by means of measuring lymphocyte protoporphyrinogen oxidase activity, at a time when the patient had no symptoms. Eighteen years later the patient presented with a firm enlargement of the liver.Results: Histologic examination showed a well-differentiated HCC. The diagnosis was confirmed by positive immunostaini...

M. Seip - One of the best experts on this subject based on the ideXlab platform.

  • Congenital erythropoietic Porphyria: a family study.
    Clinical genetics, 2008
    Co-Authors: L. Eriksen, M. Seip
    Abstract:

    We present the results of a study of the porphyrin-forming enzymes in the erythrocytes of a recently detected case of CBP, in the immediate family, and in the family of a second cousin who died in infancy with a clinical picture similar lo that seen in the present patient. Except for a moderate increase in the activity of the uroporphyrinogen synthetase in the patient's lysates no patological changes have been found either in the patient or in any of the other persons studied. Our findings do not exclude the possibility that impaired activity of the isomerase (uroporphyrinogen-III-cosynthetase) plays a role, but they do indicate that this is not the only or even the most important metabolic error in the present type of erythropoictic Porphyria. A study of the kinship between the two families seems to make a simple autosomal recessive in. heritance unlikely, hut does not exclude dominant inheritance by a rare single gene with low penetrance carried by the fathers. It is possible that the present case may represent a type of Porphyria variegata in which the metabolic defect in porphyrin biosynthesis is located not in the liver hut in the bone marrow.

J. Germanaud - One of the best experts on this subject based on the ideXlab platform.

  • A case of association between hepatocellular carcinoma and Porphyria variegata.
    Scandinavian journal of gastroenterology, 1994
    Co-Authors: J. Germanaud, F. Luthier, X. Causse, R. Kerdraon, D. Grossetti, D. Gargot, Y. Nordmann
    Abstract:

    Germanaud J, Luthier F, Causse X, Kerdraon R, Grossetti D, Gargot D, Nordmann Y. A case of association between hepatocellular carcinoma and Porphyria variegata. Scand J Gastroenterol 1994;29:671-672Background: A correlation between acute intermittent Porphyria or Porphyria cutanea tarda and hepatocellular carcinoma (HCC) has been noted in several studies, but only one case of association between HCC and Porphyria variegata has been reported. We therefore report another case of association between HCC and Porphyria variegata.Methods: A 54-year-old nurse with familial Porphyria variegata who developed an HCC was studied. The diagnosis of Porphyria variegata was made in the course of a familial survey by means of measuring lymphocyte protoporphyrinogen oxidase activity, at a time when the patient had no symptoms. Eighteen years later the patient presented with a firm enlargement of the liver.Results: Histologic examination showed a well-differentiated HCC. The diagnosis was confirmed by positive immunostaini...

A Kühnel - One of the best experts on this subject based on the ideXlab platform.

  • Studies on coproporphyrin isomers in urine and feces in the Porphyrias.
    Clinica Chimica Acta, 1999
    Co-Authors: A Kühnel, U Gross, K Jacob, Manfred O. Doss
    Abstract:

    Abstract The urinary and fecal distribution and the relative proportions of the four coproporphyrin (copro) isomers I–IV were analysed in 20 healthy subjects and in patients suffering from one of the seven common types of hepatic or erythropoietic hereditary Porphyrias. The ratios of copro isomers I–IV were analyzed by ion-pair high-performance liquid chromatography (HPLC). Observations showed significantly increased proportions of fecal copro isomer I and decreased proportions of copro isomers III, II and IV in erythropoietic Porphyrias. In acute hepatic Porphyrias the excretion of fecal copro isomer III is dominant (isomer III=58.4±24.0%; x ±S.D.) and significantly higher (P x ±S.D.) and chronic hepatic Porphyrias (isomer III=25.8±7.6%; x ±S.D.). The increased proportions of fecal copro isomer III proved to be important for the diagnosis of hereditary coproPorphyria and Porphyria variegata independent of the clinical phase existing. These last two acute hepatic Porphyrias also showed markedly elevated percentages of the fecal atypical isomers II and IV. In urine significantly decreased proportions of copro isomer I in acute hepatic Porphyrias (isomer I=12.3±6.0%; x ±S.D.) could be observed as compared with non-acute Porphyrias (isomer I=53.7±15.2%; x ±S.D.). Conversely, the proportion of urinary copro isomer III was significantly higher in acute hepatic Porphyrias (isomer III=81.4±6.4%; x ±S.D.). As expected, the greatest amounts of urinary copro isomer I were found in congenital erythropoietic Porphyria (isomer I=92.0±3.3; x ±S.D.) and protoPorphyria with hepatobiliary complications (isomer I=81.3±10.7; x ±S.D.). The atypical urinary copro isomers II and IV were detected in all types of Porphyrias ranging from 0.1 to 11.5%. The combined amounts of copro isomers II and IV show a significantly decreased percentage in congenital erythropoietic Porphyria as compared with all other types of hereditary Porphyrias. In conclusion, we demonstrate that the characteristic pattern of the copro isomer constellations I–IV in the various types of Porphyrias are of differential diagnostic importance. The inversion of the I to III ratio in feces in hereditary coproPorphyria and Porphyria variegata allows the recognition of gene carriers.

  • Studies on coproporphyrin isomers in urine and feces in the Porphyrias.
    Clinica chimica acta; international journal of clinical chemistry, 1999
    Co-Authors: A Kühnel, U Gross, K Jacob, M O Doss
    Abstract:

    The urinary and fecal distribution and the relative proportions of the four coproporphyrin (copro) isomers I-IV were analysed in 20 healthy subjects and in patients suffering from one of the seven common types of hepatic or erythropoietic hereditary Porphyrias. The ratios of copro isomers I-IV were analyzed by ion-pair high-performance liquid chromatography (HPLC). Observations showed significantly increased proportions of fecal copro isomer I and decreased proportions of copro isomers III, II and IV in erythropoietic Porphyrias. In acute hepatic Porphyrias the excretion of fecal copro isomer III is dominant (isomer III = 58.4+/-24.0%; x+/-S.D.) and significantly higher (P < 0.001) than in erythropoietic Porphyrias (isomer III = 15.3+/-7.7%; x+/-S.D.) and chronic hepatic Porphyrias (isomer III = 25.8+/-7.6%; x+/-S.D.). The increased proportions of fecal copro isomer III proved to be important for the diagnosis of hereditary coproPorphyria and Porphyria variegata independent of the clinical phase existing. These last two acute hepatic Porphyrias also showed markedly elevated percentages of the fecal atypical isomers II and IV. In urine significantly decreased proportions of copro isomer I in acute hepatic Porphyrias (isomer I = 12.3+/-6.0%; x+/-S.D.) could be observed as compared with non-acute Porphyrias (isomer I = 53.7+/-15.2%; x+/-S.D.). Conversely, the proportion of urinary copro isomer III was significantly higher in acute hepatic Porphyrias (isomer III= 81.4+/-6.4%; x+/-S.D.). As expected, the greatest amounts of urinary copro isomer I were found in congenital erythropoietic Porphyria (isomer I =92.0+/-3.3; x+/-S.D.) and protoPorphyria with hepatobiliary complications (isomer I = 81.3+/-10.7; x+/-S.D.). The atypical urinary copro isomers I1 and IV were detected in all types of Porphyrias ranging from 0.1 to 11.5%. The combined amounts of copro isomers II and IV show a significantly decreased percentage in congenital erythropoietic Porphyria as compared with all other types of hereditary Porphyrias. In conclusion, we demonstrate that the characteristic pattern of the copro isomer constellations I-IV in the various types of Porphyrias are of differential diagnostic importance. The inversion of the I to III ratio in feces in hereditary coproPorphyria and Porphyria variegata allows the recognition of gene carriers.