The effects of old and recent migration waves in the distribution of HBB*S globin gene haplotypes

Sickle cell hemoglobin is the result of a mutation at the sixth amino acid position of the beta () globin chain. The HBB*S gene is in linkage disequilibrium with five main haplotypes in the -globin-like gene cluster named according to their ethnic and geographic origins: Bantu (CAR), Benin (BEN), Senegal (SEN), Cameroon (CAM) and Arabian-Indian (ARAB). These haplotypes demonstrated that the sickle cell mutation arose independently at least five times in human history. The distribution of S haplotypes among Brazilian populations showed a predominance of the CAR haplotype. American populations were clustered in two groups defined by CAR or BEN haplotype frequencies. This scenario is compatible with historical records about the slave trade in the Americas. When all world populations where the sickle cell gene occurs were analyzed, three clusters were disclosed based on CAR, BEN or ARAB haplotype predominance. These patterns may change in the next decades due to recent migrations waves. Since these haplotypes show different clinical characteristics, these recent migrations events raise the necessity to develop optimized public health programs for sickle cell disease screening and management

Twenty years of neonatal screening for sickle cell disease in Brazil : the challenges of a continental country with high genetic heterogeneity

Sickle cell disease (SCD) is the most common inherited hematological disease worldwide. The benefits of diagnosis and early intervention have led to the wide dissemination of public health programs worldwide. Through neonatal screening programs, it is possible to reduce morbidity and mortality in the first 5 years of life. The prophylactic use of penicillin, the anti-pneumococcal vaccine and other intensive care, increase the survival and quality of life of people with SCD. The aim of this study is to present the 20-year history of screening for hemoglobinopathies in Brazil and its challenges. From 2001 to 2019, an average of 2,400,000 children were screened per year nationwide, with the coverage being of 82,16%. The screening of 54,9% of newborns is collected up to their 5th day of life. The prevalence of SCD was 1:2,263 newborns; therefore, it was the second most-common disease detected by the program of Brazil, being only after hypothyroidism (1/2,175 live births). The healthcare system should provide the necessary infrastructure to confirm the diagnosis of newborns and to provide appropriate counseling and treatment. The early diagnosis and treatment, as well as the follow-up with a multidisciplinary team, are fundamental to the survival rate and the quality of life of patients

Neonatal screening for congenital adrenal hyperplasia in Southern Brazil : a population based study with 108,409 infants

Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder associated with inborn errors of steroid metabolism. 21-hydroxylase enzyme deficiency occurs in 90 to 95% of all cases of CAH, with accumulation of 17 hydroxyprogesterone (17-OHP). Early diagnosis of CAH based on newborn screening is possible before the development of symptoms and allows proper treatment, correct sex assignment, and reduced mortality rates. This study describes the results obtained in the first year of a public CAH screening program in the state of Rio Grande do Sul, Brazil. Methods: We reviewed the screening database in search of babies with suspected CAH, that is, altered birthweight adjusted 17-OHP values at screening. The following data were analyzed for this population: screening 17-OHP values, retest 17-OHP values, serum 17-OHP values for those with confirmed CAH on retest, maternal and newborn data, and family history of CAH. For the screening program, 17-OHP levels are determined on dried blood spots obtained in filter paper with GSP solid phase time-resolved immunofluorescence. Results: Of 108,409 newborns screened, eight were diagnosed with CAH (four males, four females). The incidence of CAH in the state was 1:13,551. Six cases were identified as classic salt-wasting CAH and two were cases of virilizing CAH. The positive predictive value (PPV) of the initial screening (before diagnostic confirmation) was 1.6%. The overall rate of false positive results was 0.47%. The number of false positive results was higher among newborns with birth weight < 2000 g. Conclusion: The present results support the need for CAH screening by the public health care system in the state, and show that the strategy adopted is adequate. PPV and false positive results were similar to those reported for other states of Brazil with similar ethnic backgrounds