Clinical and haematological features of Non-Deletional alpha thalassaemia mutations in singapore

Abstract

Aims Non-deletional mutations of the α-globin gene are rare causes of alpha thalassaemia. Our study aims to characterise the frequency, haematological and clinical features of non-deletional forms of alpha thalassemia in patients who presented to the Singapore National Thalassaemia Registry (NTR) from 1997 to 2012. Methods A list of patients with non-deletional α-globin mutations were generated from laboratory records at the NTR. The relevant patient casenotes were retrieved for clinical details. Results There were 83 patients identified. The three most common α-globin chain mutations were Hb Constant-Spring (CS) (47%), Hb Quong Sze (QS) (14.5%) and Hb Adana (CD59) (12%). There were distinct ethnic differences noted in the distribution of the mutations, as the majority of patients with HbCS (46%) and all patients with HbQS were of Chinese ethnicity whereas most patients with Hb Adana (93%) were of Malay ethnicity. The majority of patients were asymptomatic carriers. Most patients with a thalassaemia intermedia phenotype had HbH disease, co-inheriting deletional α-globin mutations with non-deletional mutations, most commonly --SEA/αCS α in 80% of cases. Coinheritance of Hb Adana / Hb CS (αCS α / α a) in particular was associated with considerable clinical heterogeneity, ranging from asymptomatic carriers to transfusion dependence. Discussion Non-deletional α-globin chain mutations are associated with diverse clinical and haematological features, depending on the specific mutation and interaction with other a and β-globin chain mutations.