| dc.description.abstract | Objectives: To examine associations between the alpha-thalassemia (-Thal) genotypes and the S gene cluster haplotypes (S haplotypes) with clinical and hematological features in a population of children derived from the Newborn Screening Program of Minas Gerais (NSPMG) and followed-up at the Blood Center of Belo Horizonte (HBH) of HEMOMINAS Foundation. Methods: children with electrophoretic profile compatible with sickle cell anemia (SS or S0-thalassemia) screened by NSP-MG between 01/01/1999 to 12/31/2006 and followed-up at HBH were included in a randomized retrospective cohort study. Data were collected from patients medical records at HBH. All patients were followed-up for a minimum of two years and a half, up to 6/30/2009. Genotyping of -Thal was performed by multiplex PCR (alleles: -3.7; -4.2; --SEA; --FIL; --MED; -()20.5 e --THAI). S haplotypes were determined by PCR-RFLP. Results: 221 children were analyzed, 119 (53.8%) females and 102 (46.2%) males. The age ranged from 2.5 to 10.4 years. Two hundred and eight (94.1%) were homozygous for the S allele and 13 (5,9%) were S0-thal. Of the 208 SS subjects, 58 (27.9%) were heterozygous (-3.7/) and three (1.4%) homozygous for -Thal (-3.7/-3.7). Of the 13 S0-thal subjects, five (38.5%) were heterozygous (-3.7/). Among the 208 SS subjects, 82 (39.43%) were CAR/CAR, 69 (33.17%) Ben/CAR, 49 (23.56%) Ben/Ben, two (0.96%) CAR/Atp, two (0.96%) Ben/Atp, two (0.96%) Arab-Indian/Ben and two (0.96%) could not be genotyped. Of 412 S chromosomes genotyped in homozygous subjects for S hemoglobin (SS), 57% were CAR type, 41.5% were Ben, 0.5% were Arab-Indian e 1% were atypical. In homozygous subjects for S hemoglobin, the presence of -Thal was significantly associated with decreased levels of MCV, MCH, WBC and reticulocytes, and not with the levels of total Hb, Hb F and platelets. There was no significant association between S haplotypes and total Hb, Hb F, MCV, MCH, WBC and reticulocyte levels. Platelet count was significantly higher in the group with Ben/CAR genotype when compared with the Ben/Ben and CAR/CAR. There was no significant association between the presence of -Thal and the frequency of episodes of acute chest syndrome, blood transfusions and acute splenic sequestration. The presence of -Thal was strongly associated with decreased risk of cerebrovascular disease (abnormal transcranial Doppler or clinical stroke; P=0.007). There was no significant association between S haplotypes and the frequency of episodes of acute xiv chest syndrome, blood transfusions, acute splenic sequestration and cerebrovascular disease. Conclusions: The most important significant association found was between co-inheritance of -Thal and decreased risk of cerebrovascular disease. Neither the presence/absence of - Thal nor S haplotypes can alone predict the clinical course of the disease. Other modulating factors should be investigated to subphenotype the disease and thus be used together as a clinical tool in monitoring patients. It should be noted that the sample of children has come from a single source and was randomized; follow-up was uniform and done in a single blood center, what reinforces the conclusions of the study. | |
