Molecular Characterization in Two Families Bearing Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) IN Rosario, Argentina.

Abstract 5093 Introduction: G6PD deficiency is a frequent worldwide enzymopathy, with sex-linked inheritance, the gene that codifies the enzyme localizes at the X chromosome. Males are hemizygous (Hem) for disease, while women are heterozygous (Het), i.e. carriers, and very rarely homozygous, or double heterozygous and consequently, develop disease. There are over 120 deficient molecular variants observed in Afro-Americans and in the malaria endemic region of the Mediterranean Basin. In previous studies in Argentina we have reported a low prevalence, 0,2-0,3 %, although the predominant molecular variants are unknown. Most of deficiencies are clinically detected when the patient is submitted to oxidative stress produced by infections, therapeutic drugs, or Vicia fava ingestion, develops an acute hemolytic anemia (AHA) of variable severity. Materials and Methods: Two male patients and their families were studied. 1) A1: 45y aged male, with AHA after bean ingestion, as well as the following relatives: mother (M1); sister (S1); three nephews (N1, N2, N3) and a niece (N4) without positive AHA history. 2) A2: 55y aged male, with two AHA episodes in childhood and adolescence, one of them associated with an infection, and the mother (M2). The evaluation clinical and hematological of the patients were normal Laboratory assays: Hemogram, Hemoglobin (Hb) (Coulter AcT10); Reticulocytes (Ret); Brewer test (B.T.); Heinz bodies (HB); Cytochemical method modified (Gurbuz, N; et al): NV: 86,8 % positive cells (CYT); Enzymatic activity (EA) Kinetic Method (Beutler-OMS): NV: 8.0±1.6 G6PD/gHb IU and Polymerase Chain Reaction with Enzyme Restriction (PCR-ER) for characterization of different variants: G6PDMed(563G□T), G6PD A376(A□G), G6PD A376(A□G) 202(G□A); G6PD A 376(A□G) 680 (G□T) y G6PD A 376(A□G) 968 (T□C). Results: Conclusions: The EA confirmed the deficit of probands and nephews N1 and N3 without previous AHA history. The heterozygous character of females was not defined by this method but PCR-ER and CYT mod. supported the obliged carriers heterozygosis and the potential ones, demonstrating that CYT is more sensitive for carrier detection than other screening techniques or EA. The deficient phenotype was correlated with the detected variants, since the Mediterranean G6PD: G6PD Med(563G□T) (Type II, OMS) and G6PD A376(A□G) 202(G□A) (Type III, OMS) are associated with AHA induced by infections or Vicia Fava ingestion. The finding in Argentina of these two variants, that are frequent in the Mediterranean region, it is in accordance with the fact that our population has mainly Italian, Spanish (family 1) and Jewish (family 2) ancestors. The detection of deficient without hemolysis, as well as carriers is of the utmost importance in genetic counseling. Disclosures: No relevant conflicts of interest to declare.