DIAGNOSIS OF ACUTE INTERMITTENT PORPHYRIA IN NORTHERN SWEDEN - AN EVALUATION OF MUTATION ANALYSIS AND BIOCHEMICAL METHODS

Objective. To validate the use of a recently observed guanine to adeni ne mutation in exon 10 in the porphobilinogen deaminase (PBGD) gene as a diagnostic marker of acute intermittent porphyria (AIP). To evaluat e the efficiency of the traditional biochemical diagnostic methods. De sign. Matched and blinded case-control study (1:4). Setting. A primary health care centre in Arjeplog, the National Porphyria Research Unit and a department of clinical genetics in Stockholm. Subjects. A total of 48/49 (98%) patients over the age of 15 years living in Arjeplog wi th AIP, diagnosed according to standard clinical and biochemical crite ria. For each AIP patient, four controls were matched for age, sex and geographical area and 164/196 (86%) participated. In the validity stu dy, 35 patients were selected as indisputable AIP gene carriers, accor ding to strict biochemical criteria, and 92 matched controls were sele cted with strict exclusion criteria. Main outcome measures. Validity, specificity and sensitivity of DNA diagnosis for this AIP mutation. Sp ecificity and sensitivity of traditional biochemical methods. Results. Validity study: the mutation was found in all 35 individuals classifi ed as carriers of AIP. None of the 92 controls had the mutation. Evalu ation study: all 48 AIP gene carriers, diagnosed by traditional method s, had the mutation, as had one of the control persons. In an inconclu sive group of five persons with heredity for AIP, two had a positive D NA test. Conclusions. The PBGD mutation analysis was found to have ful l specificity and sensitivity and can be used as the sole diagnostic m ethod in the family complex studied, representing the major AIP mutati on in Sweden. The traditional diagnostic methods, used in optimal comb inations, work in most cases, but they do not show high precision. How ever, they must be used when the specific mutation in the PBGD gene is not known.