Clinical and haematological characteristics of 38 individuals with Hb G-Makassar in Malaysia

Haemoglobin (Hb) G-Makassar is a rare Hb variant. It presents a diagnostic challenge as it imitates sickle Hb (Hb S) in standard electrophoresis and high-performance liquid chromatography assays requiring DNA analysis to confirm diagnosis. Both have point mutations in codon 6, exon 1 in the beta-globin (HBB) gene with different pathogenicities. This study describes the clinical phenotype, haematology and genotype of Hb G-Makassar. Clinical and laboratory data of 38 cases of Hb G-Makassar over 8 years were analysed. Hb G-Makassar was confirmed by a direct sequencing of HBB gene and co-inheritance of alpha-thalassaemia determined through multiplex gap-PCR and multiplex Amplification Refractory Mutation System polymerase chain reaction. All cases were Malays, predominantly from Terengganu (n = 20, 52.6%). There were 14 (36.8%) males and 24 (63.2%) females with median age of 25 years. Majority (n = 33, 86.8%) had features of thalassaemia trait with mean +/- SD for Hb, mean cell volume (MCV) and mean cell haemoglobin (MCH) as 13.21 g/dL +/- 1.69, 73.06 +/- 4.48 fL and 24.71 +/- 1.82 pg, respectively. None had evidence of haemolysis or thromboembolic complications. Six genotypes were identified; ssG-Makassar/ss,alpha alpha/alpha alpha (n = 19, 50.0%), ssG-Makassar/ssE,alpha alpha/alpha alpha (n = 4, 10.5%), ssG-Makassar/ssNewYork,alpha alpha/alpha alpha (n = 1, 2.6%), ssG-Makassar/ss,alpha alpha/-alpha (n = 11, 28.9%), ssG-Makassar/ss,alpha alpha/alpha Adana alpha (n = 2, 5.3%) and ssG-Makassar/ss,alpha alpha/-SEA (n = 1, 2.6%). The ssG-Makassar/ss,alpha alpha/alpha alpha showed that features of thalassaemia trait with mean +/- SD for Hb, MCV and MCH were 13.74 g/dL +/- 2.40, 76.18 +/- 6.02 fL and 25.79 +/- 2.41 pg, respectively. This is the largest study reporting a significant number of Hb G-Makassar in Malaysia. Although the mutation is similar to Hb S, the phenotype is benign. image