ClinVar

Hb Agrinio was discovered by Hall et al. (1993) in 3 individuals of Greek origin with an atypical form of Hb H disease (613978) characterized by a severe hypochromic, microcytic anemia. Hall et al. (1993) indicated that the mutation consisted of a T-to-C transition in codon 29 of the HBA2 gene causing a leucine-to-proline transition. Although each affected individual was a compound heterozygote for Hb Agrinio and a previously described mutation affecting the poly(A) addition signal of the HBB gene (141900.0383), simple heterozygotes for the leu29-to-pro mutation have the phenotype of the alpha-thalassemia trait.

Traeger-Synodinos et al. (1998) reported the first case of homozygosity for Hb Agrinio. The leu29-to-pro amino acid substitution in alpha-2-globin was caused by a CTG-to-CCG transition. The 12-month-old Greek proband presented with marked hypochromic microcytic anemia, a very low level of Hb H, rare Hb H inclusions, and a balanced alpha/non-alpha biosynthesis ratio. At the age of 13 years, the proband had a clinical phenotype compatible with mild thalassemia intermedia with moderate anemia (Hb = 7-8 g/dL), normal growth and development, slight splenomegaly, and minimal bone changes, while Hb H and inclusion bodies were not detected.