Urinary excretion of porphyrins, porphobilinogen and δ-aminolaevulinic acid following an attack of acute intermittent porphyria

Abstract

Our study highlights the difficulties of using urinary analysis for diagnosing recurrent attacks, and also raises important questions about the pathophysiology of the condition.

High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria

“…18 When stained with the vital dyes Hoechst 33342 and propidium iodine, HRECs appeared more frequently apoptotic compared with the vehicle-treated cells (Figure 4a). In addition, ALA+PBG induced PARP (polyADP ribose polymerase) cleavage 19 (Figure 4b), and HRECs were more frequently positive for TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining (Figure 4c), which confirms that apoptosis is activated in human epithelial cells in culture by ALA+PBG.…”

Phase I open label liver-directed gene therapy clinical trial for acute intermittent porphyria

“…The differences in the residual endogenous PBGD activity among the participants may also explain the lack of a dose-effect relation observed in this clinical trial. It should also be noted that some AIP patients may be asymptomatic despite marked elevation of heme precursors (12,13).…”

“…The standard cut-off scores of BDI-II are: minimal depression (0-9), mild depression (10)(11)(12)(13)(14)(15)(16)(17)(18); moderate depression (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) and severe depression . The standard cutoff scores of BAI are low anxiety (0-21), moderate anxiety (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and severe anxiety (36-63).…”

“…These episodes are triggered by factors that activate hepatic heme synthesis including exposure to drugs (like barbiturates, sulfonamides), hormonal changes, infections or starvation (1,2,7). Clinical disease occurs with very low prevalence (1 in 185,000) (8), but epidemiologic figures based on the incidence of acute attacks greatly underestimate the number of individuals with the genetic defect, which in Sweden is as high as 1 in 10,000 (9, 10) and 1 in 1,675 in France (11), indicating that a large proportion of affected individuals exhibit an asymptomatic form of the disease, in some cases with high ALA and PBG levels in urine (12,13).…”

Molecular characterisation of acute intermittent porphyria in a cohort of South African patients and kinetic analysis of two expressed mutants

“…This is facilitated by the dipyrromethane (DPM) cofactor, which is covalently linked to the enzyme in its active site cleft 1. In AIP, porphyrins and their precursors PBG and 5-aminolevulinic acid may be produced in excess and excreted in urine during and for many years after an acute attack 2. Biochemical diagnosis of AIP is based on the measurement of these urinary precursors, the presence of a plasma porphyrin fluorescence peak at 619 nm when excited at ±400 nm and the determination of erythrocyte HMBS activity.…”