89 MOLECULAR CHARACTERISATION OF G6PD DEFICIENCY Address for correspondence and reprint requests: Professor Ainoon Othman, Haematology Unit, Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia. Malaysian J Pathol 2004; 26(2) : 89 – 98 Complete molecular characterisation of glucose-6-phosphate dehydrogenase (G6PD) deficiency in a group of Malaysian Chinese neonates Othman AINOON, MBBS,DCP, *Nem Yun BOO, MBBS, FRCP, Yuang Hong YU, BBiomed Sc (Hons),MSc, Soon Keng CHEONG, FRCP,FRCPA, Hussin Noor HAMIDAH, MBBch, DCP and Jee Hiang LIM BBiomed Sc (Hons), MSc. Haematology Unit, Department of Pathology and *Department of Paediatrics, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur. Abstract We performed DNA analysis on cord blood samples of 128 Chinese male neonates diagnosed as G6PD deficiency in Hospital Universiti Kebangsaan Malaysia by a combination PCR-restriction enzyme digest technique, Single Stranded Conformation Polymorphism analysis and DNA sequencing. We found 10 different G6PD-deficient mutations exist. The two commonest alleles were G6PD Canton 1376 G>T (42.3%) and Kaiping 1388 G>A (39.4%) followed by G6PD Gaohe 592 G>A (7.0%), Chinese-5 1024 C>T, Nankang 517 T>C (1.5%), Mahidol 487 G>A (1.6%), Chatham 1003 G>T (0.8%), Union 1360 C>T (0.8%), Viangchan 871 G>A (0.8%) and Quing Yang 392 G>T (0.8%). Sixty eight percent (88/125) neonates in this study had neonatal jaundice and 29.7% developed hyperbilirubinemia >250 μmol/l. The incidence of hyperbilirubinemia >250 μmol/l was higher in G6PD Kaiping (43.8%) than G6PD Canton (22%) (p< 0.05). There was no significant difference in the incidence of neonatal jaundice, mean serum bilirubin, mean age for peak serum bilirubin, percentage of babies requiring phototherapy and mean duration of phototherapy between the two major variants. None of the 88 neonates required exchange transfusion. In conclusion we have completely characterized the molecular defects of a group of Chinese G6PD deficiency in Malaysia. The mutation distribution reflects the original genetic pool and limited ethnic admixture with indigenous Malays. Key words: Glucose-6-phosphate dehydrogenase, G6PD, molecular variants, Chinese INTRODUCTION Glucose-6-phosphate dehydrogenase deficiency is the commonest enzymopathy in humans, estimated to affect 400 million individuals worldwide. G6PD-deficient individuals are usually asymptomatic but acute haemolysis may occur with oxidative stress induced by ingestion of drugs, certain types of food, exposure to certain chemical substances or when there is accompanying infection or hypoxia. Rarely, it may cause chronic non-spherocytic haemolytic anemia. One of the most important complications of G6PD deficiency is severe neonatal hyperbilirubinemia and the risk of developing kernicterus, a problem especially seen in G6PD- deficient individuals in the Mediterranean and Asia. 1,2,3,4 To date at least 130 mutations have been identified to cause G6PD deficiency in various populations in the world. 5 Advances in molecular techniques have allowed the molecular characterisation of G6PD gene in any population to be carried out with ease. G6PD deficiency is common in Malaysia with an overall incidence of 3.1% among males and is more prevalent in ethnic Malays and Chinese and less common among the Indians. 6,7 It is an important cause of severe neonatal jaundice and kernicterus. All newborn babies are screened for G6PD deficiency as part of a national programme to prevent complications of severe hyperbilirubinemia and kernicterus. Earlier, we reported the existence of 4 mutations in a small group of Malaysian Chinese male G6PD-deficient individuals and subsequently reported G6PD mutations in Malays. 8,9,10 We present here the results of a complete characterization of the molecular defects of Chinese G6PD deficiency in 128 Malaysian Chinese male neonates.