The pathogenesis of acute porphyria

Detalhes bibliográficos
Autor(a) principal: Prauchner, Carlos André
Data de Publicação: 2022
Outros Autores: Tatiana Emanuelli
Tipo de documento: Artigo
Idioma: por
Título da fonte: Clinical and Biomedical Research
Texto Completo: https://seer.ufrgs.br/index.php/hcpa/article/view/126050
Resumo: Acute porphyria is a disorder characterized by neurological dysfunctions such as autonomic neuropathy, peripheral neuropathy and encephalopathy. Such dysfunctions arise from an enzymatic defect in the heme biosynthetic pathway leading to decreased heme biosynthesis and accumulation of the heme precursors 5-aminolevulinic acid (ALA) and porphobilinogen. ALA accumulation seems to be responsible for the reduced plasma melatonin levels observed in porphyria patients. This could be related to the intermittent and cyclical nature of porphyria attacks, as well as to psychological alterations observed in the prodromal phase (insomnia, depression, emotional variations). Moreover, it has been proposed that ALA-induced DNA oxidation may explain the higher incidence of primary liver carcinoma in porphyria patients who have experienced a series of acute crises when compared to asymptomatic carriers. On the other hand, it has been suggested that peripheral neuropathy may be related to heme depletion, leading to a dysfunction of nervous system heme proteins. In addition, there is evidence supporting the notion that a depletion of hepatic heme may increase tryptophan plasma levels leading to enhanced serotonin levels in the central nervous system. Such alteration could be the cause of the nausea, abdominal pain and psychomotor disturbances presented by patients.
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spelling The pathogenesis of acute porphyriaA patogênese das porfirias agudasPorfirias agudaspatogêneseácido 5-aminolevulínicohemeAcute porphyriapathogenesis5-aminolevulinic acidhemeAcute porphyria is a disorder characterized by neurological dysfunctions such as autonomic neuropathy, peripheral neuropathy and encephalopathy. Such dysfunctions arise from an enzymatic defect in the heme biosynthetic pathway leading to decreased heme biosynthesis and accumulation of the heme precursors 5-aminolevulinic acid (ALA) and porphobilinogen. ALA accumulation seems to be responsible for the reduced plasma melatonin levels observed in porphyria patients. This could be related to the intermittent and cyclical nature of porphyria attacks, as well as to psychological alterations observed in the prodromal phase (insomnia, depression, emotional variations). Moreover, it has been proposed that ALA-induced DNA oxidation may explain the higher incidence of primary liver carcinoma in porphyria patients who have experienced a series of acute crises when compared to asymptomatic carriers. On the other hand, it has been suggested that peripheral neuropathy may be related to heme depletion, leading to a dysfunction of nervous system heme proteins. In addition, there is evidence supporting the notion that a depletion of hepatic heme may increase tryptophan plasma levels leading to enhanced serotonin levels in the central nervous system. Such alteration could be the cause of the nausea, abdominal pain and psychomotor disturbances presented by patients.As porfirias agudas são causadas por uma deficiência na via de biossíntese do heme, que provoca ataques caracterizados por disfunções neuroviscerais (neuropatiaautonômica, neuropatia periférica e encefalopatia) e produção excessiva dos precursores porfirínicos, ácido 5-aminolevulínico e porfobilinogênio. O acúmulo de ácido 5- aminolevulínico parece estar envolvido na redução dos níveis de melatonina no plasma dos pacientes, o que poderia estar relacionado com o caráter intermitente e cíclico das crises de porfiria, bem como com algumas alterações psicológicas observadas na fase prodrômica (insônia, depressão, alterações emocionais). Também tem sido sugerido que efeitos oxidantes do ácido 5-aminolevulínico no DNA poderiam explicar a maior suscetibilidade de pacientes que sofreram vários ataques de porfiria ao desenvolvimento de carcinomas hepáticos. No entanto, a neuropatia periférica apresentada pelos pacientes parece não estar relacionada com os aumentos na produção de ácido 5-aminolevulínico. Sugere-se que ela possa estar relacionada a uma depleção de heme que poderia prejudicar o funcionamento de hemoproteínas no sistema nervoso. Além disso, existem evidências convincentes de que a depleção do heme hepático nos pacientes pode provocar um aumento nos níveis de triptofano circulantes, com possíveis conseqüências no sistema nervoso central, tais como aumento nos níveis de serotonina, provocando náuseas, dores abdominais e distúrbios psicomotores e psiquiátricos.HCPA/FAMED/UFRGS2022-07-22info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPeer-reviewed Article"A Convite dos Editoresapplication/pdfhttps://seer.ufrgs.br/index.php/hcpa/article/view/126050Clinical & Biomedical Research; Vol. 22 No. 1 (2002): Revista HCPAClinical and Biomedical Research; v. 22 n. 1 (2002): Revista HCPA2357-9730reponame:Clinical and Biomedical Researchinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSporhttps://seer.ufrgs.br/index.php/hcpa/article/view/126050/85609http://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessPrauchner, Carlos André Tatiana Emanuelli2022-09-16T16:34:06Zoai:seer.ufrgs.br:article/126050Revistahttps://www.seer.ufrgs.br/index.php/hcpaPUBhttps://seer.ufrgs.br/index.php/hcpa/oai||cbr@hcpa.edu.br2357-97302357-9730opendoar:2022-09-16T16:34:06Clinical and Biomedical Research - Universidade Federal do Rio Grande do Sul (UFRGS)false
dc.title.none.fl_str_mv The pathogenesis of acute porphyria
A patogênese das porfirias agudas
title The pathogenesis of acute porphyria
spellingShingle The pathogenesis of acute porphyria
Prauchner, Carlos André
Porfirias agudas
patogênese
ácido 5-aminolevulínico
heme
Acute porphyria
pathogenesis
5-aminolevulinic acid
heme
title_short The pathogenesis of acute porphyria
title_full The pathogenesis of acute porphyria
title_fullStr The pathogenesis of acute porphyria
title_full_unstemmed The pathogenesis of acute porphyria
title_sort The pathogenesis of acute porphyria
author Prauchner, Carlos André
author_facet Prauchner, Carlos André
Tatiana Emanuelli
author_role author
author2 Tatiana Emanuelli
author2_role author
dc.contributor.author.fl_str_mv Prauchner, Carlos André
Tatiana Emanuelli
dc.subject.por.fl_str_mv Porfirias agudas
patogênese
ácido 5-aminolevulínico
heme
Acute porphyria
pathogenesis
5-aminolevulinic acid
heme
topic Porfirias agudas
patogênese
ácido 5-aminolevulínico
heme
Acute porphyria
pathogenesis
5-aminolevulinic acid
heme
description Acute porphyria is a disorder characterized by neurological dysfunctions such as autonomic neuropathy, peripheral neuropathy and encephalopathy. Such dysfunctions arise from an enzymatic defect in the heme biosynthetic pathway leading to decreased heme biosynthesis and accumulation of the heme precursors 5-aminolevulinic acid (ALA) and porphobilinogen. ALA accumulation seems to be responsible for the reduced plasma melatonin levels observed in porphyria patients. This could be related to the intermittent and cyclical nature of porphyria attacks, as well as to psychological alterations observed in the prodromal phase (insomnia, depression, emotional variations). Moreover, it has been proposed that ALA-induced DNA oxidation may explain the higher incidence of primary liver carcinoma in porphyria patients who have experienced a series of acute crises when compared to asymptomatic carriers. On the other hand, it has been suggested that peripheral neuropathy may be related to heme depletion, leading to a dysfunction of nervous system heme proteins. In addition, there is evidence supporting the notion that a depletion of hepatic heme may increase tryptophan plasma levels leading to enhanced serotonin levels in the central nervous system. Such alteration could be the cause of the nausea, abdominal pain and psychomotor disturbances presented by patients.
publishDate 2022
dc.date.none.fl_str_mv 2022-07-22
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Peer-reviewed Article"
A Convite dos Editores
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://seer.ufrgs.br/index.php/hcpa/article/view/126050
url https://seer.ufrgs.br/index.php/hcpa/article/view/126050
dc.language.iso.fl_str_mv por
language por
dc.relation.none.fl_str_mv https://seer.ufrgs.br/index.php/hcpa/article/view/126050/85609
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv HCPA/FAMED/UFRGS
publisher.none.fl_str_mv HCPA/FAMED/UFRGS
dc.source.none.fl_str_mv Clinical & Biomedical Research; Vol. 22 No. 1 (2002): Revista HCPA
Clinical and Biomedical Research; v. 22 n. 1 (2002): Revista HCPA
2357-9730
reponame:Clinical and Biomedical Research
instname:Universidade Federal do Rio Grande do Sul (UFRGS)
instacron:UFRGS
instname_str Universidade Federal do Rio Grande do Sul (UFRGS)
instacron_str UFRGS
institution UFRGS
reponame_str Clinical and Biomedical Research
collection Clinical and Biomedical Research
repository.name.fl_str_mv Clinical and Biomedical Research - Universidade Federal do Rio Grande do Sul (UFRGS)
repository.mail.fl_str_mv ||cbr@hcpa.edu.br
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