ACUTE INTERMITTENT PORPHYRIA IN CATALONIA (SPAIN)

Acute intermittent porphyria (AIP) is an autosomal dominant disorder with incomplete penetrance, caused by a deficiency of porphobilinogen deaminase (PBG-D) enzyme and characterised by acute neuropathic attacks. High prevalence is known in Sweden and in other areas of Europe. In Spain AIP occurs with very low prevalence but it may be underestimated. Material: Since 1992 fourteen patients with PAI attended the Hospital Clinic of Barcelona. We present the clinical, biochemical, enzymatic and genetic analysis of 8 of these patients and 17 close relatives. Methods: We analysed (a): urinary excretion of porphobilinogen (PBG) and delta-aminolevulinic acid (ALA); (b) erythrocyte PBG-D activity; (c) DNA analysis through SSCP and sequencing the PBG-D gene. Results: Increased PBG and ALA urinary excretion and decreased erythrocyte PBG-D activity were observed in all the AIP patients. Moreover, seven cases of asymptomatic AIP were found in the relatives by means of these techniques. Five PBG-D gene mutations have been identified. Three of the mutations detected in four of the families have been previously reported in other countries (730delCT in exon 12, 340insT and G11R in exon 7). Two of the mutations identified correspond to novel mutations; one of them is present in 3 of the 8 families studied (37.5%). A strong correlation between the presence of any of the mutations and a low PBG-D activity has been observed. Conclusions: The prevalence of AIP in Spain may be much higher than previously estimated. Therefore porphyrin, enzymatic and genetic analysis must be performed in the relatives in order to detect asymptomatic carriers. AIP in Spain is also a heterogeneous disease and two novel mutations have been identified, one of them could be particularly prevalent in this area.