The Hemoglobin E Thalassemias

Abstract

Hemoglobin E (HbE) is an extremely common structural hemoglobin variant that occurs at high frequencies throughout many Asian countries. It is a b-hemoglobin variant, which is produced at a slightly reduced rate and hence has the phenotype of a mild form of b thalassemia. Its interactions with different forms of a thalassemia result in a wide variety of clinical disorders, whereas its coinheritance with b thalassemia, a condition called hemoglobin E b thalassemia, is by far the most common severe form of b thalassemia in Asia and, globally, comprises approximately 50% of the clinically severe b-thalassemia disorders.

The Role of the Inherited Disorders of Hemoglobin, the First “Molecular Diseases,” in the Future of Human Genetics

“…HbE is an extremely common structural variant that occurs at a very high frequency in the eastern half of the Indian subcontinent and throughout Southeast Asia, reaching carrier frequencies of up to 70% of the population in parts of northeastern Thailand (109). Because the underlying mutation, in addition to producing a structural hemoglobin variant, activates a cryptic splice site (75) (33). Another feature of this disease is its phenotypic instability during the early years of development; some babies and young children who appear to have mild disease switch to a much more severe form later in their development.…”

A Journey in Science: Early Lessons from the Hemoglobin Field

“…One of the best examples of the remarkable phenotypic diversity of the hemoglobin disorders is Hb E β thalassemia, which, globally, accounts for approximately 50% of all severe cases of β thalassemia and which reaches its highest frequency in the eastern half of south Asia and throughout southeast Asia (41). It results from compound heterozygosity for Hb E and a variety of different β thalassemia mutations.…”

“…In a survey of over 200 patients with this condition in Sri Lanka over the last 15 years, and by a detailed analysis of the clinical phenotypes of these patients at least four times a year, it has been possible to make some progress toward an understanding of the reasons for the remarkable heterogeneity of the condition. It ranges from a severe form of thalassemia similar to β thalassemia major, requiring lifelong transfusion, to a disorder characterized by relatively normal growth and development and quality of life (albeit at a relatively low hemoglobin level, which is not much different than in individuals with the severe phenotype) (41,42).…”

Diagnostic difficulties in homozygous hemoglobin E disorders

“…It might go undiagnosed in Hb E trait as Hb A is expected to be present. However, this could be an instrument related issue as there are no reports of this occurrence in other analyzers [6,7]. The second problem associated with homozygous Hb E disorder is the amount of Hb E present.…”