Acute intermittent porphyria in childhood: a population‐based study

Abstract

To establish age-adjusted reference intervals of urinary delta-aminolaevulinic acid (U-ALA) and porphobilinogen (U-PBG) in children, and to analyse the frequency and type of clinical manifestations of acute intermittent porphyria (AIP) in childhood. Concentrations of U-ALA and U-PBG in healthy children aged 3-16y were analysed. In a population-based study in northern Sweden of 61 children aged < 18 y with DNA-verified AIP, the clinical manifestations of AIP in childhood were analysed prospectively (up to 2.5 y). Initially the children underwent a standardized investigation (anamnesis, physical examination, laboratory tests). Instructions were issued to keep a structured diary and to provide urine samples for ALA and PBG analyses in all situations of suspected AIP attacks (prospectively). Reference intervals for U-ALA and U-PBG showed age-group variations in children. Baseline levels of U-ALA and U-PBG are increased in gene carriers, one-quarter of them exceeding the 90th percentile of age- and gender-matched controls. Baseline levels did not distinguish symptomatic from non-symptomatic children in a short-term perspective. Clinical evidence of AIP attacks was found in 10% of child AIP gene carriers; in all cases the first attack occurred before the age of 15 y. AIP symptoms in children may be vague and of short duration and U-ALA and U-PBG levels are often elevated only slightly or not at all; thus, symptoms and signs may differ from those in adults. Children of AIP gene carriers should be DNA tested, followed up and carefully instructed on preventive measures to avoid developing manifest AIP.