Alpha-Thalassemia Carrier due to –α^3.7 Deletion: Not So Silent

Abstract

Background/Objective: Alpha-thalassemia is one of the most prevalent genetic diseases, with the-α 3.7 deletion being the most common mutation. Molecular studies have suggested mechanisms to explain the mild phenotype of "silent carrier" heterozygotes. However, the correlation between the clinical laboratory picture and the-α 3.7 heterozygous state remains unclear, thus we chose to investigate. Methods: We analyzed the medical files of 192 children evaluated for microcytosis at our tertiary center between 2007 and 2017 and diagnosed as heterozygotes for the-α 3.7 deletion. Additional α-thalassemia mutations, iron deficiency anemia, and β-thalassemia were ruled out. Laboratory parameters were compared to age-and sex-matched reference values. Results: The-α 3.7 carriers had significantly lower Hb and mean corpuscular volume (MCV) than the reference population, and significantly higher red blood cell counts across all age groups. The greatest reduction in Hb level appeared among male adolescents, while MCV was consistently 2 SDs lower than normal in most patients older than 2 years. Conclusion: Heterozygosity for the-α 3.7 deletion was associated with clinically significant microcytosis and mild anemia in our pediatric population. In the absence of iron deficiency and β-thalassemia, this finding provides a diagnosis for mild microcytic anemia, making additional investigations of microcytosis unnecessary.

Characterization of the Molecular Spectrum of a-Thalassemia Mutations in the Western Province of Saudi Arabia and Recommendation for Premarital Screening

“…Mean Hb was 12.3g/dL, mean RBC was 5.6 x1012/l, mean MCV was 67 fl, mean MCH was 21.9pg as shown in Table (1). The HGB H disease cases were significantly associated with lower Hb, RBC, when compared to α -Thalathemia minor/trait cases while, there was non significant differences between both groups regarding age, gender, MCV, MCH as shown in Table (2). Our study estimates the type of α -thalassemia mutations genotype and allele frequencies in a total of 39 patients with α -thalassemia as introduced in Table (3).…”

“…Mutations involving 3 α-globin genes (--/-α), give rise to Hb H disease. Deletion of all 4 alpha-genes (--/--) causes Hb Bart'shydrops fetalis, a condition that results in fetal death [2]. People with genotype α0-thalassemia(--/αα) or 3 genes deletion (--/-α), are carriers of Hb Bart hydrops fetalis.…”

Secondary hemophagocytic syndrome in an acquired immunodeficiency syndrome and Alpha-thalassemia patient infected with Talaromyces marneffei: A case report and literature review

“…Thalassemia is a hereditary disorder characterized by the production of an unbalanced globin chain, which results in ineffective erythropoiesis, increased hemolysis, and deranged iron homoeostasis [3] . The – α 3.7 deletion represents the most common mutation in Alpha -thalassemia, causing clinically significant microcytosis and mild anemia [10] . Considering the presence of small cell hypochromic anemia and the patient's origin from the Guangxi province, a region with a high prevalence of thalassemia, genetic analysis was performed.…”

Random forest classifiers trained on simulated data enable accurate short read-based genotyping of structural variants in the alpha globin region at Chr16p13.3

“…The α -thalassemia genetic trait consists of any of a group of mutations, mainly deletions, that occur within the α -globin locus in the human chromosome 16 (16p13.3)(1,2). In general, these mutations result in reduced expression of the α globin genes HBA1 and HBA2 , and can sometimes lead to severe anemia requiring blood transfusion or even cause death in-utero(3,4). There is evidence that loss of any one of the four copies of the α globin genes, resulting in an α -thalassemia silent carrier state, is protective against severe malaria, suggesting that higher allele frequencies observed for these mutations in tropical and subtropical climates (malaria belt) may be the result of natural selection(5,6).…”

“…The 𝛼-thalassemia genetic trait consists of any of a group of mutations, mainly deletions, that occur within the 𝛼-globin locus in the human chromosome 16 (16p13.3) (1,2). In general, these mutations result in reduced expression of the 𝛼 globin genes HBA1 and HBA2, and can sometimes lead to severe anemia requiring blood transfusion or even cause death in-utero (3,4).…”