title: Diagnosis of acute intermittent porphyria in northern Sweden: an evaluation of mutation analysis and biochemical methods.
abstract: OBJECTIVE
  To validate the use of a recently observed guanine to adenine mutation in exon 10 in the porphobilinogen deaminase (PBGD) gene as a diagnostic marker of acute intermittent porphyria (AIP). To evaluate the efficiency of the traditional biochemical diagnostic methods.
  
  
  METHODS
  Matched and blinded case-control study (1:4).
  
  
  METHODS
  A primary health care centre in Arjeplog, the National Porphyria Research Unit and a department of clinical genetics in Stockholm.
  
  
  METHODS
  A total of 48/49 (98%) patients over the age of 15 years living in Arjeplog with AIP, diagnosed according to standard clinical and biochemical criteria. For each AIP patient, four controls were matched for age, sex and geographical area and 164/196 (86%) participated. In the validity study, 35 patients were selected as indisputable AIP gene carriers, according to strict biochemical criteria, and 92 matched controls were selected with strict exclusion criteria.
  
  
  METHODS
  Validity, specificity and sensitivity of DNA diagnosis for this AIP mutation. Specificity and sensitivity of traditional biochemical methods.
  
  
  RESULTS
  Validity study: the mutation was found in all 35 individuals classified as carriers of AIP. None of the 92 controls had the mutation. Evaluation study: all 48 AIP gene carriers, diagnosed by traditional methods, had the mutation, as had one of the control persons. In an inconclusive group of five persons with heredity for AIP, two had a positive DNA test.
  
  
  CONCLUSIONS
  The PBGD mutation analysis was found to have full specificity and sensitivity and can be used as the sole diagnostic method in the family complex studied, representing the major AIP mutation in Sweden. The traditional diagnostic methods, used in optimal combinations, work in most cases, but they do not show high precision. However, they must be used when the specific mutation in the PBGD gene is not known.
authors.affiliation: Primary Health Care Centre, Arjeplog, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Andersson
authors.forename: S
authors.initials: S
authors.lastname: Thunell
authors.forename: Y
authors.initials: Y
authors.lastname: Floderus
authors.forename: C
authors.initials: C
authors.lastname: Forsell
authors.forename: G
authors.initials: G
authors.lastname: Lundin
authors.forename: M
authors.initials: M
authors.lastname: Anvret
authors.forename: L
authors.initials: L
authors.lastname: Lannfelt
authors.forename: L
authors.initials: L
authors.lastname: Wetterberg
authors.forename: F
authors.initials: F
authors.lastname: Lithner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006579:Heterozygote; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics*; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D017354:Point Mutation; D017118:Porphyria, Acute Intermittent / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013548:Sweden
chemical_list: D011163:Hydroxymethylbilane Synthase