RESUMEN
Background: Human hemoglobin of G-Makassar and hemoglobin E (Hb E) are hemoglobin variants that affect Beta (ß) globin. Hb G-Makassar is a very rare variant while Hb E is estimated to affect at least one million people worldwide. Both Hb G-Makassar and Hb E can be inherited in the heterozygous, homozygous or compound heterozygous state. This case series describes the characteristics of four individuals with compound heterozygosity for Hb G-Makassar/Hb E cases in Malaysia. To the best of our knowledge, these are the only four individuals with this genotype reported in the literature. Case Series: We present four cases of compound heterozygosity for Hb G-Makassar/Hb E identified from October 2014 to January 2021. All the cases were incidental findings whereby the screening Hb analysis showed the presence of peaks in both Hb S and Hb E zones on capillary electrophoresis (CE) and cation-exchange high-performance liquid chromatography (HPLC). Molecular analysis confirmed the findings of compound heterozygous Hb G-Makassar/Hb E. Two cases had a history of anemia secondary to unrelated conditions that resolved with treatment of the underlying cause. The other two cases were asymptomatic individuals who were detected through Malaysia's National Thalassemia Screening program. On the last follow-up, all the individuals were well, non-transfusion dependent, and had no reported history of chronic anemia, bleeding, hemolysis or thromboembolism complications. Conclusion: The cases reported here highlight the possibilities for rare compound heterozygous states in multi-ethnicity populations such as Malaysia. Compound heterozygous Hb G-Makassar/Hb E individuals are clinically silent with laboratory values suggesting microcytic and hypochromic red blood cells. Further local epidemiology or population studies with genotyping tests are required for a better understanding of the diversity of its clinical phenotype.
RESUMEN
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 ß-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 13.21 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,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 13.74 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.
RESUMEN
Human hemoglobin of G-Makassar variant has been reported very rarely with Beta Thalassemia. In year 1969 Hb GMakassar was first identified in Makassar, Sulawesi (Celebes), Republic of Indonesia. The disease was first published in 1969 and 33 years later it has been reported at a family of Thailand origin. We report a 45-yearold Malay man who was investigated for anemia and thrombocytopenia then diagnosed with Hb G-Makassar. This finding describes as a new Hemoglobin GMakassar discovered in Malaysia after 14 years diagnosed in Thailand.