α-thalassaemia

Abstract

Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia.It is probably the most common monogenic gene disorder in the world and is especially frequent in Mediterranean countries, South-East Asia, Africa, the Middle East and in the Indian subcontinent. During the last few decades the incidence of alpha thalassaemia in North-European countries and Northern America has increased because of demographic changes. Compound heterozygotes and some homozygotes have a moderate to severe form of alpha thalassaemia called HbH disease. Hb Bart's hydrops foetalis is a lethal form in which no alpha-globin is synthesized. Alpha thalassaemia most frequently results from deletion of one or both alpha genes from the chromosome and can be classified according to its genotype/phenotype correlation. The normal complement of four functional alpha-globin genes may be decreased by 1, 2, 3 or all 4 copies of the genes, explaining the clinical variation and increasing severity of the disease. All affected individuals have a variable degree of anaemia (low Hb), reduced mean corpuscular haemoglobin (MCH/pg), reduced mean corpuscular volume (MCV/fl) and a normal/slightly reduced level of HbA2. Molecular analysis is usually required to confirm the haematological observations (especially in silent alpha-thalassaemia and alpha-thalassaemia trait). The predominant features in HbH disease are anaemia with variable amounts of HbH (0.8-40%). The type of mutation influences the clinical severity of HbH disease. The distinguishing features of the haemoglobin Bart's hydrops foetalis syndrome are the presence of Hb Bart's and the total absence of HbF. The mode of transmission of alpha thalassaemia is autosomal recessive. Genetic counselling is offered to couples at risk for HbH disease or haemoglobin Bart's Hydrops Foetalis Syndrome. Carriers of alpha+- or alpha0-thalassaemia alleles generally do not need treatment. HbH patients may require intermittent transfusion therapy especially during intercurrent illness. Most pregnancies in which the foetus is known to have the haemoglobin Bart's hydrops foetalis syndrome are terminated due to the increased risk of both maternal and foetal morbidity.

An investigation of the protective effect of alpha+‐thalassaemia against severe Plasmodium falciparum amongst children in Kumasi, Ghana

“…However, there appears to be no cure for Hb Bart's Hydrops Foetalis Syndrome and the HbH disease. (Harteveld and Higgs 2010) The best treatment available today consists of frequent blood transfusions (every two to three weeks) with iron chelation therapy (e.g. deferoxamine)…”

“…These regulate the normal individual alpha globin synthesis (Galanello et al, 1998). However the expression of these genes is dependent on a Multispecies Conserved Sequences (MCS-R2) or the erythroid-specific DNAsel hypersensitivity sites (HS-40) located 40 kb upstream from the alpha globin clusters which have been shown to express alpha globin genotype (Harteveld and Higgs 2010) and appears to be the major regulator. The deletion of MCS-R2 (HS-40) therefore results in an alpha-thalassaemia phenotype.…”

“…The non-deletional forms of α-thalassaemias have been described where these conditions have been observed to present with a more severe reduction in α chain synthesis than the deletional types (Harteveld and Higgs 2010 (Bain, 2006).…”

“…These are the α-thalassaemia mental retardation syndrome on chromosome 16 (ATR16), the α-thalassaemia mental retardation X-linked syndrome (ATR-X) and α-thalassaemia myelodysplastic syndrome (ATMDS). In these conditions, deletions remove not only the  globin genes but also a number of other genes around them (Harteveld and Higgs 2010) (Weatherall, 2001a) Alpha+-thalassaemia is predominant in the tropics and sub-tropics, with its prevalence ranging between 1% and 98% (Higgs et al, 1989).…”

Normal cognitive functioning in a patient with Hb Bart’s hydrops successfully cured by hematopoietic SCT

“…1 Abolition of a-globin chains, which are critically required for fetal erythropoiesis to produce Hb F (a2g2), causes affected fetuses to die in utero or shortly after birth, and is associated with several maternal complications. 2,3 In Thailand, over 5000 pregnancies each year are at risk of this condition, with 1250 new cases expected, because approximately 5-10% of Thailand's population are carriers of a 0 -thalassemia traits. 4,5 A program for prevention and control of severe thalassemia syndromes, including Hb Bart's hydrops, was initiated in Thailand 1994.…”