Twelve Cases of Hb Manitoba [α102(g9)ser→arg]: the Fluctuation in the Variant Expression.

Hb Manitoba [alpha 102(G9)Ser -> Arg] is a rare alpha chain variant with diverse ethnic origins. It is mildly unstable with an expression of around 10.0-14.2% in the heterozygous state in most literature. In this study, 12 cases of Hb Manitoba [11 cases carried Hb Manitoba II (HBA1: c.309C>A) and one case carried Hb Manitoba IV (HBA1: c.307A>C)] were detected during a wide-spectrum study of alpha chain variants in the UK. Fluctuation in variant expression from 6.9 to 15.2% of total Hb on high performance liquid chromatography (HPLC) would pose a diagnostic dilemma in routine laboratories. Focusing on the variant expression, the median of Hb Manitoba was around 11.5% of total Hb in three cases, apparently with normal hemoglobin (Hb), and normal red blood cell (RBC) indices. Two cases showed a higher expression (13.9 and 15.2%) and five cases showed a lower expression (6.9-9.9%). The common alpha-thalassemia (alpha-thal) -alpha(3.7) (rightward) deletion coexisted with one case of increased Hb Manitoba expression. Iron (or other nutrient) deficiency was likely the cause of decreased Hb Manitoba percentage in this study. The alpha 73(EF2)Val -> Val (alpha 2) (HBA2: c.222G>T) polymorphism is published for the first time and coexisted with two cases. The Cap +14 (C>G) (HBA2: c.-24C>G) polymorphism coexisted with another case in a heterozygous state. In conclusion, the fluctuation in variant expression can cause a diagnostic dilemma, especially in routine laboratories. Screening for the common -alpha(3.7) deletion and iron deficiency is recommended when an alpha chain variant is suspected.