The W198X and R173W mutations in the porphobilinogen deaminase gene in acute intermittent porphyria have higher clinical penetrance than R167W. A population-based study

In northern Sweden, 468 patients with DNA-verified acute intermittent porph yria (AIP) were registered. A higher prevalence of manifest AIP was found i n patients with mutations W198X: and R173W when separately compared with mu tation R167W, indicating higher clinical penetrance; Signs of increased ser iousness of the disease were also found in patients with the W198X and R173 W mutations in relation to the number and duration of attacks, impaired ren al function and chronic disability. One explanation could be lower PBGD enz yme activity resulting from the W198X and R173W mutations than from the R16 7W mutation, though other factors might also be the cause.