Clinical and biochemical characteristics and genotype-phenotype correlation in 143 Finnish and Russian patients with acute intermittent porphyria

Medicine (Baltimore). 2005 Jan;84(1):35-47. doi: 10.1097/


Acute intermittent porphyria (AIP), resulting from a deficiency of porphobilinogen deaminase (PBGD) in heme biosynthesis, is genetically heterogeneous and manifests with variable penetrance. The clinical outcome, prognosis, and correlation between PBGD genotype and phenotype were investigated in 143 Finnish and Russian AIP patients with 10 mutations (33G-->T, 97delA, InsAlu333, R149X, R167W, R173W, R173Q, R225G, R225X, 1073delA). Thirty-eight percent of the patients had experienced 1 or more acute attacks during their lives. The proportion of symptomatic patients has decreased dramatically from 49% to 17% among patients diagnosed before and after 1980, respectively. Patients with the R167W and R225G mutations showed lower penetrance (19% and 11%, respectively) and recurrence rate (33% and 0%, respectively) than patients with other mutations (range, 36%-67% and 0%-66%, respectively). Moreover, urinary excretions of porphyrins and their precursors were significantly lower in these patients (porphobilinogen [PBG], 47 +/- 10 vs. 163 +/- 21 micromol/L, p < 0.001; uroporphyrin, 130 +/- 40 vs. 942 +/- 183 nmol/d, p < 0.001). Erythrocyte PBGD activity did not correlate with PBG excretion in remission or with the clinical severity of the disease. Mutations R167W and R225G resulted in milder biochemical abnormalities and clinical symptoms indicating a milder form of AIP in these patients. In all AIP patients, normal PBG excretion predicted freedom from acute attacks. The risk of symptoms was highest for female patients with markedly increased PBG excretion (>100 micromol/L). Proper counseling contributed to the prevention of subsequent attacks in 60% of previously symptomatic and in 95% of previously symptom-free patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Pain / etiology
  • Adolescent
  • Adult
  • Analysis of Variance
  • Erythrocytes / metabolism
  • Female
  • Genotype
  • Humans
  • Hydroxymethylbilane Synthase / metabolism
  • Hydroxymethylbilane Synthase / urine*
  • Logistic Models
  • Male
  • Middle Aged
  • Phenotype
  • Porphyria, Acute Intermittent / complications
  • Porphyria, Acute Intermittent / genetics*
  • Porphyria, Acute Intermittent / metabolism
  • Precipitating Factors
  • Statistics, Nonparametric


  • Hydroxymethylbilane Synthase