Mutations in Acute Intermittent Porphyria Detected by ELISA Measurement of Porphobilinogen Deaminase

Summary: To study the existence of different mutations in acute intermittent porphyria, erythrocyte por-phobilinogen 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 ^g/gHb) was quantified using a recently developed double-sandwich ELISA. The ratio of enzyme catalytic activity to the concentration of enzyme protein was expressed s the porphobilinogen specific activity (nkat/g). The controls had a mean porphobilinogen deaminase concentration of 160 ± 35 μg/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 μg/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 μg/gHb, and a highly significant reduction in specific activity to 234 ± 48 nkat/g, were found, which indicates the presence of a different mutation. Introduction have a reduced activity of porphobilinogen Acute intennittent porphyria is a dominantly inher- deaminase1). Measurement of the erythrocyte activity ited (1) inborn error of haem biosynthesis characte- of the enzyme has proved to be a valuable tool in th