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 a hepatic disorder named Acute Intermittent Porphyria (AIP); the acute porphyria is more frequent in Argentina. 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 Centro de Investigaciones sobre Porfirinas y Porfirias (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 was 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 foreign family from Paraguay is discussed. Moreover, it can be noted that 38 new families were found carrying the most frequent mutation in Argentina (p.G111R), increasing to 55.66% the prevalence of this genetic change in our population and adding further support to our previous hypothesis of a founder effect for this mutation in Argentina. Identification of patients with an overt AIP is 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.

Molecular Analysis of 55 Spanish Patients with Acute Intermittent Porphyria

“…In our series, no correlation between genotype-phenotype was observed, which is in agreement with previous studies [37,38]. Intragenic polymorphisms were studied elsewhere so as to establish a possible relation with clinical manifestation, however no association was found [37].…”

Acute Intermittent Porphyria: Predicted Pathogenicity ofHMBSVariants Indicates Extremely Low Penetrance of the Autosomal Dominant Disease

“…However, only six of these had <3% of WT expressed activity or reduced thermostability. Review of the original reports for the other six variants identified 13 reportedly symptomatic AIP patients who had variants encoding p.T59I [Schneider‐Yin et al., ], p.E86V [Floderus et al., ], p.R225Q [Floderus et al., ; von Brasch et al., ], or p.R321H [Schuurmans et al., ; von Brasch et al., ; Anyaegbu et al., ; Cerbino et al., ]. However, the pathogenicity of most of these patients was not verified by elevated urinary ALA or PBG levels with the exception of (1) three patients with p.R321H who also had a second and pathogenic HMBS mutation [von Brasch et al., ; Cerbino et al., ]; and (2) one patient with p.R321H who had significantly increased urinary ALA or PBG concentrations, suggesting the presence of an unidentified second and pathogenic mutation [Anyaegbu et al., ] (Supp.…”

Acute intermittent porphyria precipitated by atazanavir/ritonavir

“…Of the acute porphyrias, which include variegate porphyria, hereditary coproporphyria and δ-aminolevulinic acid (ALA) dehydratase deficiency porphyria, AIP is the most common. 1–4…”