AN OVERVIEW OF PATHOGENIC VARIANTS IN ACUTE INTERMITTENT PORPHYRIA IN ARGENTINA

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

Mar del Plata

Congreso; CONGRESO DE BIOCIENCIAS 2023; 2023

Sociedad Argentina de Investigación Clínica

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. Thisstudy 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.135. 603. ANALYSIS OF THE ROLE OF NR1I2 GENE VARIANTSIN HEPATIC PORPHYRIAS ONSETKiara Martínez Yucovsky1, Isabella Moltrasio1, ElizabethWoo1, Tomas Santillán2, Sebastián Yun2, Viviana Melito2,3,Laura Varela2, Victoria Parera2, Ana Buzaleh2,3, Johanna Zuccoli21 Escuelas Técnicas ORT2 CIPYP, UBA-CONICET3 Departamento de Química Biológica, FCEN, UBAPorphyrias are due to heme enzymes deficiencies: Porphobilinogendeaminase in Acute Intermittent Porphyria (AIP), and Uroporphyrinogendecarboxylase in Porphyria Cutanea Tarda (PCT).Several factors, as therapeutic drugs, are needed for the onset ofthese hepatic diseases. NR1I2 gene encodes for PXR transporter;NM_022002.3:c.196C>T and NM_003889.4:c.-22-7659C>T variantsaffect the expression of many proteins like ABCB1 and CYP3A4.The aim was to evaluate the role of PXR SNVs in AIP andPCT triggering. Cohorts studied: Control, symptomatic AIP (S-AIP),asymptomatic AIP (L-AIP) and PCT. Individuals signed informedconsent. PCR-RFLP was used for genotyping. S-AIP allelic frequencyfor c.196C>T (0.13, p