Table 4.

Common disorders related to the HBB gene.

HBB disorder	Genotype	Phenotype	% HbA
β-thalassemia minor	ββ0, ββ+ (i.e., carriers)	Asymptomatic or mild microcytic hypochromic anemia may be present.	92–95%
β-thalassemia intermedia	β+β+, β+β0 (typically with alpha gene deletion)	Later onset, microcytic hypochromic anemia, jaundice, hepatosplenomegaly, risk of iron overload.	10–30%
β-thalassemia major	β0β0, β+β+, β+β0	Onset within 2 years of life, severe microcytic hypochromic anemia, hepatosplenomegaly, failure to thrive.	0%
Sickle cell disease	HbS/HbS [homozygous for c.20A>T (p.Glu7Val)]	Onset in infancy, severe anemia, splenomegaly, jaundice, episodes of severe pain including swelling of hands and feet, stroke in childhood	Low to absent

β, wildtype HBB locus; β⁰, pathogenic variant resulting in no production of HBB protein (e.g., deletion); β⁺, pathogenic variant resulting in reduced production of HBB protein (e.g., promoter variant).