title: Molecular and biochemical studies of acute intermittent porphyria in 196 patients and their families.
abstract: BACKGROUND
  Acute intermittent porphyria (AIP) is a metabolic disease with clinical manifestations that mimic other abdominal, neurologic, or mental crises. We studied the diagnostic accuracy of current laboratory tests during an acute attack and in remission.
  
  
  METHODS
  Since 1966, we have studied all known Finnish AIP patients (n = 196) and their families (n = 45) and identified the porphobilinogen deaminase (PBGD) mutation in each family. Diagnoses or exclusions of AIP were based on clinical data (including family history), biochemical tests, and in 239 cases, mutation testing. We retrospectively evaluated the diagnostic accuracy of erythrocyte PBGD activity, urinary excretion of porphobilinogen (PBG) and delta-aminolevulinic acid, and urinary and fecal excretion of porphyrins in these patients.
  
  
  RESULTS
  Measurement of urinary PBG identified all 35 AIP patients studied during an acute attack. The mean excretion of PBG was 50-fold above the reference interval, although the intraindividual increases were modest (1.6- to 4.0-fold). In the mutation-screened population, urinary PBG analysis identified only 85% of 81 AIP patients studied during remission, but by ROC curve analysis it was nonetheless the best of the biochemical tests. It was increased <or=2-fold in 29% of healthy relatives. Erythrocyte PBGD activity was decreased in only 84% of AIP patients, with results within the reference interval mainly in the variant form of AIP; it was decreased in 23% of healthy relatives.
  
  
  CONCLUSIONS
  Measurement of urinary PBG is the best biochemical test for AIP, although it is unspecific and does not distinguish AIP from other acute porphyrias. Because the acute increase in PBG is often modest, the medical history, signs, and symptoms must be evaluated carefully during an acute attack. In addition, because biochemical analyses often remain indeterminate in remission, mutation analysis is needed to exclude or confirm the diagnosis of AIP.
authors.affiliation: Department of Medicine, Division of Endocrinology, University Hospital of Helsinki, 00029 HUS Helsinki, Finland. raili.kauppinen@hus.fi
authors.forename: Raili
authors.initials: R
authors.lastname: Kauppinen
authors.forename: Mikael
authors.initials: M
authors.lastname: von und zu Fraunberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000652:urine; D004247:DNA / Q000097:blood; D005190:Family; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011162:Porphobilinogen / Q000652:urine; D017118:Porphyria, Acute Intermittent / Q000175:diagnosis* / Q000235:genetics*; D011166:Porphyrins / Q000032:analysis / Q000652:urine; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA
chemical_list: D011166:Porphyrins; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D004247:DNA; D011163:Hydroxymethylbilane Synthase