The pathogenesis of acute porphyria

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 precu...

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Detalles Bibliográficos
Autores: Prauchner, Carlos André, Tatiana Emanuelli
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:Brasil
Institución:Universidade Federal do Rio Grande do Sul (UFRGS)
Repositorio:Clinical and Biomedical Research
Idioma:portugués
OAI Identifier:oai:seer.ufrgs.br:article/126050
Acceso en línea:https://seer.ufrgs.br/index.php/hcpa/article/view/126050
Access Level:acceso abierto
Palabra clave:Porfirias agudas
patogênese
ácido 5-aminolevulínico
heme
Acute porphyria
pathogenesis
5-aminolevulinic acid
Descripción
Sumario: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.