DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia

Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional alpha-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable alpha-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-alpha(3.7)), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Pakse (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional alpha-thalassaemia mutations. Duplex-PCR was used to confirm Hb Pakse and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (alpha(codon59)alpha/alpha(CS)alpha) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Pakse for the first time in a Malaysian patient (alpha(codon59)alpha/alpha(Pakse)alpha) after nine years of being misdiagnosis with Hb Adana and HbCS (alpha(codon59)alpha/alpha(CS)alpha). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations.