Hb Adana [HBA2: c179G>A ( or HBA1); p. Gly60Asp] is a rare hemoglobin ( Hb) variant due to a mutation at codon 59 of the alpha 2- or alpha 1-globin gene resulting in a glycine to aspartic acid substitution. Two siblings with a unique coinheritance of Hb Adana and Hb Constant Spring (Hb CS, alpha 142, Term -> Gln, TAA>CAA; HBA2: c.427 T>C) (alpha(codon) (59)alpha/alpha(CS)alpha), were compared phenotypically with another two siblings carrying the Hb Adana mutation and a 3.7 kb deletion (alpha(codon) (59)alpha/-alpha(3.7)). Although they all had alpha-thalassemia intermedia ( alpha-TI), the former were clinically more severe than the latter. The first pair of siblings presented at a much younger age than the second pair and showed lower Hb levels and significant extramedullay hemopoiesis. Another case of a hydropic fetus as a result of Hb H/Hb Adana is also described. Their clinical phenotypes and hematological parameters are all presented for comparison.

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is the commonest cause of neonatal jaundice in Malaysia. Recently, OSMMR2000-D G6PD Assay Kit has been introduced to quantitate the level of G6PD activity in newborns delivered in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). As duration of sample storage prior to analysis is one of the matters of concern, this study was conducted to identify the stability of G6PD enzyme during storage. A total of 188 cord blood samples from normal term newborns delivered at UKMMC were selected for this study. The cord bloods samples were collected in ethylene-diamine-tetra-acetic acid (EDTA) tubes and refrigerated at 2-8 degrees C. In addition, 32 out of 188 cord blood samples were spotted on chromatography paper, air-dried and stored at room temperature. G6PD enzyme activities were measured daily for 7 days using the OSMMR2000-D G6PD Assay Kit on both the EDTA blood and dried blood samples. The mean value for G6PD activity was compared between days of analysis using Student Paired T-Test. In this study, 172 out of 188 cord blood samples showed normal enzyme levels while 16 had levels corresponding to severe enzyme deficiency. The daily mean G6PD activity for EDTA blood samples of newborns with normal G6PD activity showed a significant drop on the fourth day of storage (p < 0.005) while for samples with severely deficient G6PD activity, significant drop was seen on third day of storage (p = 0.002). Analysis of dried cord blood showed a significant reduction in enzyme activity as early as the second day of storage (p = 0.001). It was also noted that mean G6PD activity for spotted blood samples were lower compared to those in EDTA tubes for all days (p = 0.001). Thus, EDTA blood samples stored at 2-8 degrees C appeared to have better stability in terms of their G6PD enzyme level as compared to dried blood samples on filter paper, giving a storage time of up to 3 days.

Aim: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a recognised cause of severe neonatal hyperbilirubinaemia, and identifying which infants are at risk could optimise care and resources. In this study, we determined if G6PD enzyme activity (EA) and certain gene variants were associated with neonatal hyperbilirubinaemia requiring phototherapy during the first week after birth. Methods: Newborn infants with G6PD deficiency and a group with normal results obtained by the fluorescent spot test were selected for analyses of G6PD EA and the 10 commonly encountered G6PD mutations in this region, relating these with whether the infants required phototherapy before discharge from the hospital in the first week. Results: A total of 222 infants with mean gestation and birth weight of 38.3 +/- 1.8 weeks and 3.02 +/- 0.48 kg, respectively, were enrolled. Of these, n = 121 were deficient with EA = 6.76 U/g Hb, and approximately half (43%) received phototherapy in the first week after birth. The mean EA level was 3.7 U/g Hb. The EA had good accuracy in predicting phototherapy use, with area under the receiver-operating-characteristic curve of 0.81 +/- 0.05. Infants on phototherapy more commonly displayed World Health Organization Class II mutations (<10% residual EA). Logistic regression analysis showed that deficiency in EA and mutation at c. 1388G>A (adjusted odds ratio, 1.5 and 5.7; 95% confidence interval: 1.31-1.76 and 1.30-25.0, respectively) were independent risk factors for phototherapy. Conclusion: Low G6PD EA (< 6.76 U/g Hb) and the G6PD gene variant, c. 1388G>A, are risk factors for the need of phototherapy in newborn infants during the first week after birth.

Haemoglobin (Hb) Lepore is a variant Hb consisting of two alpha-globin and two delta beta-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/beta-thalassaemia and co-inheritance alpha(+)-thalassaemia (-alpha(3.7)). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.

Orang Asli are the minority indigenous people in Peninsular Malaysia and can be divided into 3 main groups (Negrito, Senoi and Proto Malay) with different six sub-ethnics under each group. Within the Senoi group, the six sub-ethnics are sub-ethnic Mah Meri, Semoq Beri, Che Wong, Jah Hut, Semai and Temiar. This study was aimed to investigate the current prevalence of alpha- and beta-thalassemia and hemoglobinopathies and their mutation types among all six sub-ethnics of Senoi Orang Asli. Blood samples from 685 Senoi participants were collected and sent immediately for routine full blood count analysis and hemoglobin sub-typing. Of 378 subjects screened, 7 subjects were found to be Hemoglobin E (HbE) beta thalassemia carriers, 13 beta thalassaemic, 35 Hemoglobin Constant Spring (HbCS) carriers, 6 compound HbE and HbCS carriers, 32 with HbE disease and 163 HbE heterozygote carriers. The findings of high HbE among Temiars and Jah Huts and high HbCS exclusively in Jah Huts in this study suggest distinct differences across sub-ethnics under Senoi group. Understanding of prevalence and wide spectrum of thalassemia and hemoglobinopathies among Senoi and Orang Asli is essential for national thalassaemia awareness and prevention program, especially in Orang Asli communities.

Erythrocytes require glucose-6-phosphate dehydrogenase (G6PD) to generate NADPH and protect themselves against hemolytic anemia induced by oxidative stress. Peroxiredoxin 2 (Prx2) is a major antioxidant enzyme that requires NADPH to recycle its oxidized (disulfide-bonded) form. Our aims were to determine whether Prx2 is more highly oxidized in G6PD-deficient erythrocytes and whether these cells are able to recycle oxidized Prx2 after oxidant challenge. Blood was obtained from 61 Malaysian neonates with G6PD deficiency (average 33% normal activity) and 86 controls. Prx2 redox state was analyzed by Western blotting under nonreducing conditions. Prx2 in freshly isolated blood was predominantly reduced in both groups, but the median level of oxidation was significantly higher (8 vs 3%) and the range greater for the G6PD-deficient population. When treated with reagent H2O2, the G6PD-deficient erythrocytes were severely compromised in their ability to recycle oxidized Prx2, with only 27 or 4% reduction after 1 h treatment with 0.1 or 1 mM H2O2 respectively, compared with > 97% reduction in control erythrocytes. The accumulation of oxidized Prx2 in oxidatively stressed erythrocytes with common G6PD variants suggests that impaired antioxidant activity of Prx2 could contribute to the hemolysis and other complications associated with the condition.

Thalassaemia is a public health problem in Malaysia, with each ethnic group having their own common mutations. However, there is a lack on data on the prevalence and common mutations among the indigenous people. This cross-sectional study was performed to determine the common mutations of - and -thalassaemia among the subethnic groups of Senoi, the largest Orang Asli group in Peninsular Malaysia. Blood samples collected from six Senoi subethnic groups were analysed for full blood count and haemoglobin analysis (HbAn). Samples with abnormal findings were then screened for - and -globin gene mutations. Out of the 752 samples collected, 255 showed abnormal HbAn results, and 122 cases showing abnormal red cell indices with normal HbAn findings were subjected to molecular screening. DNA analysis revealed a mixture of - and -globin gene mutations with 25 concomitant cases. The types of gene abnormalities detected for -thalassaemia were termination codon (T>C) Hb CS ((CS)), Cd59 (G>A) haemoglobin Adana (Hb Adana) ((Cd59)), initiation codon (ATG>A-G) ((IniCd)), two-gene deletion (-(SEA)), and single-gene 3.7-kb deletion (-(3.7)). For -thalassaemia, there were Cd26 (G>A) Hb E ((E)), Cd19 (A>G) Haemoglobin Malay (Hb Malay) ((Cd19)), and IVS 1-5 (G>C) ((IVS 1-5)).

Short tandem repeat (STR) analysis is used in chimerism monitoring after allogeneic hematopoietic stem cell transplantation (HSCT) for patients with various hematologic malignancies. Commercial forensic STR kits often contain loci with huge differences in power of discrimination (PD) across populations, causing some loci to be less informative for chimerism analysis in certain populations. This study aimed to construct a new STR multiplex panel with highly informative loci for efficient chimerism analysis. Thirteen STR markers which exhibit high PD (> 0.9) in at least 80% of 50 populations globally were selected to form a new panel and used in STR analysis of 253 Malaysian subjects. Cumulative power of discrimination (CPD) and combined power of exclusion (CPE) were determined from 253 Malaysian individuals. Loci informativity was assessed and compared to the commercial AmpFLSTR Identifiler PCR Amplification kit in 14 donor-recipient pairs. The new panel had detected 202 unique alleles including five novel alleles from the 253 individuals with high CPD and CPE (> 0.99999999999999999 and > 0.999999997 respectively). All loci from the new panel in the donor-recipient pair analysis showed higher than 50% informativity, while five loci from the commercial kit demonstrated lower than 50% informativity. Four loci from the new panel ranked the highest informativity. A sequenced allelic ladder which consists of 202 unique alleles from the 253 subjects was also developed to ensure accurate allele designation. The new 13-loci STR panel, thus, could serve as an additional powerful, accurate, and highly informative panel for chimerism analysis for HSCT patients.

A systematic review of literature was conducted to examine the effects of date fruit (Phoenix dactylifera) interventions aimed at alleviating neurological diseases in animal models. Searches were conducted on electronic databases including EMBASE, PubMed, Scopus and Web of Science as well as hand searching. Retrieved studies represented a variety of intervention approaches (types of extraction, parts of plant used) with animal models of ischemic stroke, Alzheimer's disease, and substance -induced brain damage. Phoenix dactylifera interventions were associated with reduced degeneration of neurons, reduced oxidative stress markers, improved antioxidant status and neuronal histological changes in ischemic stroke.and brain damage when compared to the control. Phoenix dactylifera was also found to reduce oxidative stress level and improve endogenous antioxidant status, lower plasma level of beta-amyloid and neuroinflammatory cytokine, improved neurobehavioral deficits and cognitive performances in the Alzheimer's group. This review suggests that there is an association between Phoenix dactylifera and improvement of neurological disease markers in animal models of neurological diseases. The effects of Phoenix dactylifera by reducing oxidative stress level and improving antioxidant status in neurological diseases render it as a potential neuroprotective agent. However, further studies are needed to confirm the role of Phoenix dactylifera in conferring neuroprotective activity.

Methods: A prospective study was conducted to investigate the effects of glucose-6-phosphate dehydrogenase (G6PD) mutation, variant uridine diphosphate glucuronosyltransferase UGT1A1 gene and hepatic organic anion transporter protein (OATP2) gene on a group of neonates. Hyperbilirubinemia was defined as a total serum bilirubin level of epsilon 250 mu mol/l. Results: Of 318 neonates, 52 (16.4%) had hyperbilirubinemia. The incidence of G6PD mutation was 5.4% (15/280) among these infants. The incidence of G6PD mutation was significantly higher in the male neonates with hyperbilirubinemia (7.8%) when compared with the normal male neonates without hyperbilirubinemia (1.8%; p = 0.03). Logistic regression analysis showed that the significant risk factors for neonatal hyperbilirubinemia were Malay ethnicity [adjusted odds ratio (OR), 2.77; 95% confidence interval (CI): 1.31-5.86; p = 0.007] and G6PD mutation (adjusted OR, 3.29; 95% CI: 1.06-10.1820; p = 0.039). The gender, birth weight and gestation age of neonates, variant c.211G > A and variant of OATP2 gene were not significant. Conclusions: Neonates with Malay ethnicity and G6PD mutation were at risk for hyperbilirubinemia.