Pathophysiology of attacks in acute hepatic porphyrias

Introduction

Hepatic heme biosynthesis has an autoregulatory system that responds to the requirements of this substance. The presence of intracellular heme exerts an inhibitory effect on the activity of the first enzyme in the heme biosynthetic chain, the enzyme ALA synthase 1 (ALAS1), thereby decreasing heme biosynthesis (Fig. 1). On the contrary, at the moment when the heme requirement increases, the low intrahepatocyte concentration results in an intense

Pathophysiology of attacks

In PHA, due to the lower activity of the enzymes involved in heme synthesis, the amount of heme produced may be insufficient to meet the needs in situations where increased heme production is required. Intense stimulation of ALAS1 activity leads to pathological accumulation of heme precursors (Fig. 1), especially delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). These precursors can be detected in elevated concentration in 

Conclusions and therapeutic aspects

From what has already been said, the treatment of acute attack of porphyria is based, in addition to symptomatic treatment (pain, neurological symptoms, etc.), on the withdrawal of the triggering factors and the rapid suppression of heme biosynthesis through the exogenous supply of hemin. As of the date of writing of this manuscript, there are preclinical data proposing the use of messenger RNA of the PBDG enzyme as an etiologic treatment aimed at normalizing heme biosynthesis....

CITATION Med Clin (Barc). 2023 Sep:159 Suppl 1:S12-S14. doi: 10.1016/j.medcli.2023.05.029. Epub 2023 Oct 10.