Acute Intermittent Porphyria in Argentina: An Update

Abstract

Porphyrias are a group of metabolic diseases that arise from deficiencies in the heme biosynthetic pathway. A partial deficiency in Hydroxymethylbilane synthase (HMBS) produces the hepatic disorder named Acute Intermittent Porphyria (AIP), the acute porphyria more frequent in Argentina. Identification of patients with an overt AIP is absolutely important because treatment depends on an accurate diagnosis but more critical is the identification of asymptomatic relatives to avoid acute attacks which may progress to death. In this paper we review the results obtained for 101 Argentinean AIP families and 6 AIP families from foreign neighbour countries studied at molecular level at CIPYP. Thirty five different mutations were found of which 14 were described for the first time in our population. The most prevalent type of mutations were the missense mutations (43%) followed by splice defects (26%) and small deletions (20%). An odd case of a double heterozygous presentation of AIP in a foreing family from Paraguay is discussed. Moreover it can be noted that 38 new families carrying the frequent mutation in Argentine, p.G111R, increased to 55,66% the prevalence of this genetic change in our population adding further support to our previous hypothesis of a founder effect for this mutation in Argentina.