Acute hepatic porphyrias for the neurologist: current concepts and perspectives

ABSTRACT

Background: Acute hepatic porphyrias represent an expanding group of complex inherited metabolic disorders due to inborn errors of metabolism involving heme biosynthesis. Objective: We aimed to review the main clinical and therapeutic aspects associated with acute hepatic porphyrias. Methods: The authors provided a wide non-systematic review of current concepts and recently acquired knowledge about acute hepatic porphyrias. Results: Acute neurovisceral attacks are the most common and life-threatening presentation of this group and are often considered the main clinical manifestation by clinicians during differential diagnosis and the start of proper diagnostic work-up for acute porphyrias. However, atypical presentations with central nervous system involvement, neuropsychiatric disturbances, and some subtypes with photosensitivity usually make the definite diagnosis difficult and late. Early therapeutic interventions are essential during emergency treatment and intercritical periods to avoid recurrent severe presentations. The availability of new disease-modifying therapeutic proposals based on small interfering RNA (siRNA)-based therapies, complementary to the classic intravenous glucose infusion and hemin-based treatments, emphasizes the importance of early diagnosis and genetic counseling of patients. Conclusions: This review article highlights the main biochemical, pathophysiological, clinical, and therapeutic aspects of acute hepatic porphyrias in clinical practice.

RESUMO

Introdução: As porfirias hepáticas agudas representam um grupo de doenças metabólicas hereditárias complexas em expansão, decorrentes de erros inatos do metabolismo, envolvendo a via de biossíntese do grupamento heme. Objetivo: realizar revisão dos principais aspectos clínicos e terapêuticos associados com as porfirias hepáticas agudas. Métodos: Os autores realizaram ampla revisão não-sistemática sobre conceitos atuais e conhecimentos recentemente adquiridos. Resultados: Ataques neuroviscerais agudos representam a apresentação clínica mais comum e de maior risco, e são comumente considerados como principal manifestação na prática clínica durante o diagnóstico diferencial e início apropriado da investigação diagnóstica para porfirias agudas. Entretanto, apresentações atípicas com envolvimento do sistema nervoso central, alterações neuropsiquiátricas e alguns subtipos com fotossensibilidade fazem com que o diagnóstico definitivo seja comumente difícil e tardio. As intervenções terapêuticas precoces são essenciais durante o tratamento emergencial e em período intercrítico evitando formas recorrentes graves. A disponibilidade de novas propostas terapêuticas modificadoras de doença baseadas em terapias com pequenas moléculas de RNA de interferência (siRNA) complementares aos clássicos tratamentos com infusão de glicose intravenosa e à base de hemina enfatiza a importância do diagnóstico precoce de tais pacientes e do aconselhamento genético. Conclusões: Este artigo de revisão destaca os principais aspectos bioquímicos, fisiopatológicos, clínicos e terapêuticos das porfirias hepáticas agudas na prática clínica.

Keywords:

Neuromuscular Diseases - Porphyria - Inborn Errors of Metabolism - Acute Intermittent Porphyria - Hepatic Porphyrias

Palavras-chave:

Doenças Neuromusculares - Porfirias - Erros Inatos do Metabolismo - Porfiria Aguda Intermitente - Porfirias Hepáticas

Authors’ contributions:

PVSS: manuscript project: conception, organization, execution (leading role in all steps); manuscript: writing of the first draft, review and critique (leading role for both). BMLB: manuscript project: conception, organization, execution (main participation in conception and organization steps); manuscript: writing of the first draft, review and critique (mild contribution in all steps). IBF: manuscript project: conception, organization, execution (leading role in conception and organization); manuscript: writing of the first draft, review and critique (main participation in writing step). EAG: manuscript project: conception, organization, execution (leading role in conception and organization); manuscript: writing of the first draft, review and critique (mild contribution for both). WBVRP: manuscript project: conception, organization, execution (leading role in all steps); manuscript: writing of the first draft, review and critique (leading role for both). ASBS: manuscript project: conception, organization, execution (leading role in all steps); manuscript: writing of the first draft, review and critique (leading role as reviewer).

Publikationsverlauf

Eingereicht: 31. März 2020

Angenommen: 07. Juni 2020

Artikel online veröffentlicht:
01. Juni 2023

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