Percorrer por autor "Faria, Teresa"
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- Deciphering the genetic modifiers of sickle cell anemia in children: the role of CYB5R3 genePublication . Nascimento, Djanira; Lopes, Pedro; Kjollerstrom, Paula; Maia, Raquel; Faria, Teresa; Faustino, PaulaIntroduction: Sickle cell anemia (SCA) is an autosomal recessive disorder caused by the c.20A>T alteration in the beta-globin gene (HBB), leading the synthesis of abnormal hemoglobin S (HbS). Under hypoxic conditions, HbS polymerizes within red blood cells (RBCs), causing them to adopt the characteristic sickle shape. This results in a clinically heterogenous disease, characterized by chronic hemolytic anemia, vaso-occlusive crises, and multi-organ damage. The CYB5R3 gene encodes the enzyme NADH-cytochrome b5 reductase 3, which plays a crucial role in protecting hemoglobin (Hb) from oxidative damage to unfunctional methemoglobin. Patients with SCA may develop methemoglobinemia, particularly under conditions of oxidative stress. This study aimed to evaluate the potential modulatory effects of a CYB5R3 variant, along with other well-established genetic modifiers within the globin genes, on the phenotypic variability of SCA in pediatric age. Methodology: Eighty-one children with SCA were followed by pediatricians at two hospitals in the Greater Lisbon area, who characterized their clinical, hematological, and biochemical phenotypes. For this specific study, CYB5R3, HBG2, HBA1, and HBA2 genes were genotyped using PCR, Sanger sequencing, and Gap-PCR. Association analyses were performed using SPSS. Results and Discussion: Co-inheritance of α-thalassemia with SCA was observed in 43.2% of the children and proved to be beneficial, as it was associated with higher RBC counts, milder anemia, and a significant reduction in hemolysis biomarkers (bilirubin and reticulocyte counts). Similarly, elevated fetal Hb levels (HbF ≥10%) were also beneficial, leading to less severe hemolytic anemia. In the HBG2 gene, the rs7482144_T allele had a frequency of 15% and was associated with higher HbF, reduced hemolytic parameters, lower HbS level, milder anemia, and a lower frequency of clinical comorbidities, except for heart disease. In the CYB5R3 gene, the rs1800457_G allele showed a very high allelic frequency of 35% and appears to exert a deleterious effect because patients carrying this allele presented with more severe anemia, elevated hemolysis biomarkers, and a greater tendency toward hepatomegaly and cardiac comorbidities. This study contributes to understanding how genetic modifiers influence SCA severity, complication risk and eventually treatment response. Identifying these factors supports personalized medicine and may help uncover new therapeutic targets.
- Newborn Screening for Sickle Cell Disease: Results from a Pilot Study in the Portuguese PopulationPublication . Rodrigues, Diogo; Marcão, Ana; Lopes, Lurdes; Ventura, Ana; Faria, Teresa; Ferrão, Anabela; Gonçalves, Carolina; Kjöllerström, Paula; Castro, Ana; Fraga, Sofia; Almeida, Marta; Maia, Tabita; Gomes, João; Lachado, Ana; Guerra, Isabel; Ferreira, Fátima; Trigo, Fernanda; Bento, Celeste; Vilarinho, LauraThe Portuguese Newborn Screening Program currently includes 28 pathologies: congenital hypothyroidism, cystic fibrosis, 24 inborn errors of metabolism, sickle cell disease and spinal muscular atrophy. This pilot study for sickle cell disease newborn screening, including 188,217 samples, was performed between May 2021 and December 2023, with phase I, including 24,130 newborns, in the Lisbon and Setubal districts and phase II, including 164,087 newborns, in the whole country. DBS samples were analyzed through capillary electrophoresis. In phase I, a high birth incidence of sickle cell disease was found (1:928 NBs), resulting from the identification of 24 HbSS and 2 HbSC patients. This birth incidence decreased but remained significant when the pilot study for sickle cell disease newborn screening was expanded to a national level, with the identification of 67 sickle cell disease patients (59 HbSS and 8 HbSC), revealing a birth incidence of 1:2449 NBs. These data suggest that this condition is becoming increasingly relevant in Portugal, thus reflecting a general European trend, where sickle cell disease is already recognized as a public health problem. Therefore, it highlights the importance of its integration into the Portuguese National Newborn Screening Program panel in January 2024, thus allowing the early identification and clinical follow-up of these patients.