WITHIN-SUBJECT BIOLOGICAL VARIATION OF THE URINARY EXCRETION OF ALA, PBG AND PORPHYRINS IN ACUTE INTERMITTENT PORPHYRIA

Acute intermittent porphyria (AIP) is characterised by attacks of abdominal, neurological and mental symptoms. The diagnosis of an acute AIP attack is based on the assumption that it is accompanied by an increased excretion of urinary porphobilinogen (PBG). However, many AIP patients have a baseline excretion of PBG 5-10 folds the upper reference value even when in remission. To be able to distinguish an increase in u-PBG caused by a porphyria attack from the natural variation of PBG excretion, it is important to know the within-subject variation of porphyrins and porphyrin precursors in urine. Fifteen patients with latent AIP or AIP in remission without symptoms for the past two years, collected morning urine samples once a week for a period of ten weeks. The urine samples were stored in -80° C, and samples from each patient were analysed in duplicates in the same runs for the heme precursors PBG, d-aminolevulinic acid (ALA), total porphyrins in addition to creatinine. The within-subject variation (CV) of PBG, ALA and porphyrins per creatinine are 18%, 20% and 28% respectively. This means that for an AIP patient with a u-PBG baseline excretion of 40.0 µmol/mmol creatinine, changes to a value between 19.6 - 60.4 PBG µmol/mmol creatinine can be explained by biological and analytical variation with a certainty of 95%.