Alpha-thalassemia is likely the most commonly occurring genetic disorder, affecting persons in many parts of the world. It is the result of an underproduction of alpha chains which can be determined by measuring the relative in vitro synthesis of alpha and non-alpha (beta+gamma+delta) chains (alpha/non-alpha = <1). The duplication of the alpha-globin gene results in the presence of the alpha2 and alpha1 genes; this duplication complicates the genetics of the alpha-thal syndrome. A normal individual has four alpha-globin genes which is indicated as alphaalpha/alphaalpha. The deletion of one alpha-globin gene (-alpha/alphaalpha) is indicated as an alpha-thal-2 heterozygosity; the same nomenclature is used for mutations in either the alpha2- or alpha1-globin gene [alpha(T)alpha/alphaalpha or alphaalpha(T)/alphaalpha]. Homozygosities for alpha-thal-2 deletions or mutations are indicated as -alpha/-alpha or alpha(T)alpha/alpha(T)alpha, alphaalpha(T)/alphaalpha(T), and compound heterozygosities as -alpha/alpha(T)alpha, -alpha/alphaalpha(T), or alpha(T)alpha/alphaalpha(T). The deletion of two alpha-globin genes from one chromosome is indicated as - -/alphaalpha and referred to as an alpha-thal-1 heterozygosity; a homozygosity (- -/- -) is a condition without alpha chain synthesis and is referred to as Hb Bart's hydrops fetalis. Combinations of alpha-thal-1 and alpha-thal-2 alleles, thus -alpha/- -, or alpha(T)alpha/- -, or alphaalpha(T)/- -, lead to a condition with only one active alpha-globin gene, or Hb H disease. The two clinically most important syndromes are hydrops fetalis and Hb H disease. The first condition is not compatible with life; the fetus or stillborn produces large quantities of Hb Bart's (gamma4), 5-20% of embryonic Hbs (mainly zeta2gamma2, zeta2beta2, zeta2delta2) and some Hb H. Hb H disease is characterized by a moderate anemia (7-10 g/dl) with severe microcytosis, hypochromia, Heinz bodies, and 5-30% Hb H (beta4) in the adult and large quantities of Hb Bart's at birth (10-25%). The detection of alpha-thalassemia was first made through the recognition of these two syndromes.
Occasionally, the nomenclature alpha°- and alpha+-thal is used. This can lead to considerable confusion: some authors name alpha-thal-1 (- -/alphaalpha) alpha°-thal and alpha-thal-2 (-alpha/alphaalpha) alpha+-thal, while others apply this nomenclature to the nondeletional alpha-thal-2 for partial (alpha+) or complete (alpha°) suppression of the synthesis of the alpha chain by the affected chromosome. This nomenclature is, therefore, not used in this compendium.
The alpha-thalassemia syndrome is complex and its description here is divided into five sections:
while a sixth section (f) reviews the various forms of Hb H disease.
a) the nondeletional alpha-thal alleles, b) the deletional alpha-thal alleles, c) alpha-globin gene mutants occurring on a chromosome with the alpha-thal-2 (-alpha/alphaalpha) deletion, d) the deletional alpha-thal-1 (- -/alphaalpha) alleles, e) the alpha-thal-1 alleles with intact alpha2- and alpha1-globin genes,