Thalassemia variants that may present as beta thalassemia intermedia

General principles: The pathophysiology of beta (β) thalassemia depends absolutely on the amount of excess unpaired alpha globin chains. Therefore, any genetic variant that increases or decreases the amount of these unpaired alpha chains (eg, by altering the rate of alpha or beta chain production or by substituting for the missing beta chains) will modify the phenotype. Disorders that present as β thalassemia intermedia, rather than as the major or minor variants, are listed below:

Homozygosity for mild forms of β+ thalassemia

Compound heterozygosity for β+/βº thalassemia

Compound heterozygosity for β thalassemia and another beta chain variant (eg, β-thal/HbE)

Coinheritance of homozygous β thalassemia with genes for increased gamma chain synthesis (ie, HPFH)

Coinheritance of homozygous β+ thalassemia with alpha thalassemia (eg, β+/β+ with -a/-a, --/aa, -a/aa, or --/-a)

Coinheritance of heterozygous β thalassemia and triplicated or quadruplicated alpha genes (eg, aa/aaa or aa/aaaa)

Dominant forms of β thalassemia^[1,2]

β+ thalassemia: reduced production of beta chains (may be mild, moderate, or severely reduced); βº thalassemia: no production of beta chains; HbE: hemoglobin E; HPFH: hereditary persistence of fetal hemoglobin.

References:

Thein SL. Is it dominantly inherited beta thalassemia or just a beta-chain variant that is highly unstable. Br J Haematol 1999; 107:12.
Thein SL. Structural Variants with a β thalassemia phenotype. In: Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management, Steinberg MH, Forget BG, Higgs DR, Nagel RL (Eds), Cambridge University Press, Cambridge 2001.

Courtesy of Stanley L. Schrier, MD.

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Thalassemia variants that may present as beta thalassemia intermedia