Jordi To-Figueras, Gregori Casals, Carlos Muñoz, Cristina Carrera, Carmen Herrero

Porphyria Unit. Biochemistry Unit. Hospital Clinic. University of Barcelona, Villarroel 170. 08036 Barcelona. Spain

Some patients with acute intermittent porphyria (AIP) present recurrently increased urinary values of porphobilinogen (PBG) and aminolevulinic acid (ALA). Therefore, the diagnose of an acute attack and the optimization of heme therapy may be problematical given the difficulty to interpret the laboratory results. In order to determine  individual reference values, we have selected six of these patients and we have (a): analyzed in duplicate the concentration of PBG, ALA and porphyrins in urine collected once a week for a period of  seven consecutive weeks; (b): studied the recorded  basal values  of PBG and ALA in urine during a three-year period; In addition, we have analyzed during 45 consecutive days the urine of one patient treated with heme-arginate. These urinary data have been contrasted with the enzymatic (erythrocyte PBG deaminase); genetic  (mutation in the AIP gene) and clinical status of the patients. The results show that, during long periods of time, the urinary time course of PBG and ALA does not present an intermittent peak/baseline pattern but a profile of regular high excretion. The within-subject biological variation (CV) of PBG, ALA and major urinary porphyrins was calculated;  This allowed to identify some  patients with  PBG reference values  20-50 folds the  upper normal limit  with a CV < 15%.  PBG and ALA concentrations  showed a good correlation but  some of the major porphyrins did not always correlated with the precursors. The three-year recorded data suggest that each  AIP patient approaches  a steady-state of  high ALA/PBG production  as a probable consequence of an enduring up-regulation of the ALA-S gene. The set point value of this steady-state appears to be independent of the activity of PBGD; the type of AIP mutation and even ,to a certain degree, the clinical status of the disease (supported by grant FIS/03/ 0489/Spain).