Mutations in acute intermittent porphyria detected by ELISA measurement of porphobilinogen deaminase.

To study the existence of different mutations in acute intermittent porphyria, erythrocyte porphobilinogen deaminase activity and enzyme protein concentration were investigated in 125 porphyria gene carriers from 31 families, and in 121 apparently healthy controls. Porphobilinogen deaminase concentration (micrograms/gHb) was quantified using a recently developed double-sandwich ELISA. The ratio of enzyme catalytic activity to the concentration of enzyme protein was expressed as the porphobilinogen specific activity (nkat/g). The controls had a mean porphobilinogen deaminase concentration of 160 +/- 35 micrograms/gHb and a specific activity of 762 +/- 127 nkat/g. Two different types of mutation causing acute intermittent porphyria were detected. The majority (91%) of gene carriers, from 25 families, had a diminished porphobilinogen deaminase concentration of 102 +/- 18 micrograms/gHb, with a slightly lowered specific activity of 634 +/- 105 nkat/g. In 9% of the gene carriers, representing six different families, an increase in porphobilinogen deaminase concentration to 269 +/- 46 micrograms/gHb, and a highly significant reduction in specific activity to 234 +/- 48 nkat/g, were found, which indicates the presence of a different mutation.