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

Abstract

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 β-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 α-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 13.21g/dL±1.69, 73.06±4.48fL and 24.71±1.82pg, respectively. None had evidence of haemolysis or thromboembolic complications. Six genotypes were identified; ßG-Makassar/ß,αα/αα (n=19, 50.0%), ßG-Makassar/ßE,αα/αα (n=4, 10.5%), ßG-Makassar/ßNewYork,αα/αα (n=1, 2.6%), ßG-Makassar/ß,αα/-α (n=11, 28.9%), ßG-Makassar/ß,αα/αAdanaα (n=2, 5.3%) and ßG-Makassar/ß,αα/-SEA (n=1, 2.6%). The ßG-Makassar/ß,αα/αα showed that features of thalassaemia trait with mean±SD for Hb, MCV and MCH were 13.74g/dL±2.40, 76.18±6.02fL and 25.79±2.41pg, 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.