The pathogenesis of acute porphyria
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | |
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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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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1799767057502306304 |