Clinical Characteristics and Outcomes of Acute Intermittent Porphyria: Insights From the European Porphyria Registry

Abstract

Background and aims: Acute intermittent porphyria (AIP) is a rare disorder with diverse clinical presentations, ranging from latent at-risk individuals to recurrent acute attacks with severe complications. Differences between clinical states and risk factors for severe outcomes remain incompletely defined.

Approach and results: In this cross-sectional study, personal, biochemical and clinical data were recorded for non-givosiran treated AIP patients across all clinical states by European porphyria expert centres into the European Porphyria Registry during 2012-2018. Logistic regression models assessed associations between clinical factors and outcomes, with disease states defined according to clinical practice at study initiation. Urinary δ-aminolevulinic acid (u-ALA) and porphobilinogen (u-PBG) were normalized to each centre's upper reference limits. Data from 239 participants were included and patients were classified as sporadic attack(s) (n = 61), recurrent (n = 49), in-remission (n = 58), asymptomatic high excreters (n = 23) and latent at-risk (n = 48). Hospitalization for an acute attack was associated with ≥ 10-fold u-PBG increase (adjusted Odds Ratios [aOR] = 22.40, 95% CI = 5.34-94.03), 4-9-fold (6.35 [2.87-14.02]) and ≥ 10-fold (177.50 [8.03-3923]) u-ALA increase, BMI < 18.5 (12.68 [2.86-56.23]) and age 20-39 (4.35 [1.82-10.42]). A 10-fold u-PBG increase (8.22 [2.31-29.28]) and a positive family history at diagnosis (0.30 [0.14-0.64]) were associated with recurrent classification. Recurrent AIP (7.28 [2.77-19.14]) and sporadic heme-treated acute attacks (5.30 [1.89-14.91]) were associated with reduced work capacity and unemployment. Chronic hypertension, chronic kidney disease and primary liver cancer were observed across all clinical groups.

Conclusions: In this multicentre European study, we describe disease burden across all clinical AIP states including non-givosiran treated recurrent patients and identify risk factors associated with hospitalization and recurrent disease.

Keywords: hydroxymethylbilane synthase (HMBS); porphobilinogen (PBG); rare diseases; recurrent acute intermittent porphyria; δ‐ aminolevulinic acid (ALA).