An overview of pathogenic variants in Acute Intermittent Porphyria in Argentina.

VARELA L; CABALLERO ALEJANDRA; GUOLO MARCELO; BUZALEH, ANA MARIA; PARERA VICTORIA

Mar del Plata

Congreso; LXXI Congreso de la Asociación Argentina de Investigación ClínicaLXX; 2023

Sociedad Argentina de Investigación Clinica

Acute Intermittent Porphyria (AIP), an autosomal dominant disorderresulting from hydroxymethylbilane synthase (HMBS) deficiency,presents with life-threatening neuroabdominal crises. More than520 variants in the HMBS gene were identified worldwide. This study aimed to analyze patients with AIP from unrelated families,focusing on genetic heterogeneity and pathogenic variants. We examined127 AIP patients diagnosed at CIPYP. Diagnosis involvedbiochemical measurements (urinary 5-aminolevulinic acid and porphobilinogen,urinary and plasma porphyrins, and blood HMBS activity)and genetic studies for identifying pathogenic variants. In thepopulation analyzed, 49 different pathogenic variants were detected.Notably, p.G111R (49%), p.Q34P (5.5%), p.R173W (4%), andc.202_203delCT (1.6%) were prominent variants. Other variationswere private to specific families. This study revealed the identificationof 4 new pathogenic variants for the Argentinian population,among them, p.(Leu49Cysfs*49) has not been previously reported.Moreover, compound heterozygosity was evident in 3 families, anddual PAI/PCT (Porphyria Cutanea Tarda) was found in another family.This study provides insights into the genetic landscape of AIP,highlighting the significance of genetic analysis for accurate diagnosisand informed medical guidance. The identification of novelvariants further enriches our understanding of the genetic basis ofAIP in the Argentinean population. Genetic analysis is indispensablein some cases to confirm AIP diagnosis. It is also relevant for theidentification of latent patients and for counseling about triggeringfactors, thereby avoiding the clinical manifestation of the disease.