Hb Stanleyville-II [α78(EF7)Asn→Lys (α2); HbA2: c.237C>A]: Incidence of 1:11,500 in a Newborn Screening Program in Brazil

Abstract

Almost 3 million babies were tested in a newborn screening program in Minas Gerais, Brazil (1998-2008); 128 who have S-like hemoglobins (Hbs) were tested for the β(S) allele and 112 were identified through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or sequencing. Hb Stanleyville-II [α78(EF7)Asn→Lys (α2); HbA2: c.237C>A] was present in 96 children (85.7%), two in a homozygous state and 94 in a heterozygous state. Its estimated prevalence was 1:11,500. Hbs Hasharon [α47(CE5)Asp→His, GAC>CAC (α2)], Ottawa [α15(A13)Gly→Arg (GGT>CGT) (α2 or α1)], G-Ferrara [β57(E1)Asn→Lys (AAC>AAA or AAG)], St. Luke's [α95(G2)Pro→Arg, C CG>C GG (α1)], Maputo [β47(CD6)Asp→Tyr (GAT>TAT)] and Etobicoke [α84(F5)Ser→Arg (AG C>AG G or CGC or AGA) (α2 or α1)] were also identified. Many children with Hbs Stanleyville-II and Hasharon also co-inherited the -α(3.7) thalassemia gene. African ancestry was recognized by parents of all 31 children with Hb Stanleyville-II who were interviewed. Mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) values were significantly lower in children with α-thalassemia (α-thal). We came to the conclusion that Hb Stanleyville-II is not so uncommon in Brazil and seems to have originated from the African slave trade. This study reinforces the importance of an accurate diagnosis of variants that have electrophoretic mobility similar to Hb S [β6(A3)Glu→Val, GAG>GTG] so that false diagnoses are avoided.

Hemoglobin variants identified in the Uganda Sickle Surveillance Study

“…Its geographic distribution encompasses many regions of Africa including Uganda, the Democratic Republic of Congo, Sudan, Kenya, and Angola, but is not restricted to these areas, reflecting worldwide African migration. 18,19 It has been described in non-African individuals as well, suggesting several points of origin. 19,20 In many cases, this Hb variant is found in association with -a 3.7 -thalassemia (rightward) deletion.…”

“…18,19 It has been described in non-African individuals as well, suggesting several points of origin. 19,20 In many cases, this Hb variant is found in association with -a 3.7 -thalassemia (rightward) deletion. 19 Historically, Hb Stanleyville II has not been shown to impact hematological indices or clinical phenotype when occurring in isolation.…”

“…19,20 In many cases, this Hb variant is found in association with -a 3.7 -thalassemia (rightward) deletion. 19 Historically, Hb Stanleyville II has not been shown to impact hematological indices or clinical phenotype when occurring in isolation. 19,21 Hb G-Pest is an a-chain variant that is the result of a single base substitution (Asp74Asn) in the second exon of a-1.…”

“…19 Historically, Hb Stanleyville II has not been shown to impact hematological indices or clinical phenotype when occurring in isolation. 19,21 Hb G-Pest is an a-chain variant that is the result of a single base substitution (Asp74Asn) in the second exon of a-1. Hb G-Pest was first identified in conjunction with another a-chain variant-Hb J-Buda-and helped demonstrate the presence of 2 a-globin genes.…”

Comments on: “Clinical, hematological and genetic data of a cohort of children with hemoglobin SD”

“…However, the Brazilian Government Directive MS # 822/01 that regulates newborn screening for hemoglobinopathies, has promoted an increase of data about hemoglobinopathies in different Brazilian regions 9, 10, 11. This associated with the use of isoelectric focusing electrophoresis (IEF) and high-pressure liquid chromatography (HPLC) as diagnostic methods, has enabled the identification of an increasing number of abnormal Hbs as well as compound heterozygous states of Hb S 12, 13, 14. An example is a paper published in this issue of the Revista Brasileira de Hematologia e Hemoterapia that shows data on a cohort of children with hemoglobin SD pattern 15 …”