Estimation and application of biological variation of urinary delta-aminolevulinic acid and porphobilinogen in healthy individuals and in patients with acute intermittent porphyria.
BACKGROUND
Diagnosis of an attack of acute intermittent porphyria (AIP) is based on the demonstration of increased concentrations of porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) in urine, but many AIP patients also have high baseline concentrations in remission. The aim of this study was to estimate the biological variations of ALA, PBG, and porphyrins in healthy individuals and AIP patients to improve interpretation of test results.


METHODS
Fifteen healthy individuals and 15 AIP patients were included, and biological variations were calculated based on urine samples collected weekly for 10 consecutive weeks. For the AIP patients, long-term variations were also estimated based on 7 samples collected through a 2-year period.


RESULTS
The porphyrin variances were inhomogeneously distributed; biological variations of porphyrins were therefore not calculated. The within-subject biological variations of ALA and PBG were 16%-20% in the short-term settings and for PBG, 25% in the long-term setting, giving reference change values of approximately 50% and 70%, respectively. The probability of detecting a 100% real change in PBG was 97% in the short-term setting and 80% in the long-term setting.


CONCLUSIONS
In an AIP patient, a 2-fold increase in PBG, independent of the baseline concentration, will be detected with a probability >80% and is most likely related to the patient's disease and not caused only by analytical and biological variation. When PBG is used in the assessment of AIP-related symptoms, both the PBG concentration in remission and the length of time since the previous sample must be considered.
Aarsand
Aasne K
AK
Norwegian Porphyria Centre, NAPOS, Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway. aasne.aarsand@helse-bergen.no
Petersen
Per Hyltoft
PH
Sandberg
Sverre
S
D000328:Adult; D000622:Aminolevulinic Acid / Q000652:urine*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011162:Porphobilinogen / Q000652:urine*; D017118:Porphyria, Acute Intermittent / Q000175:diagnosis*; D011336:Probability; D012016:Reference Values
D011162:Porphobilinogen; D000622:Aminolevulinic Acid