MyMedR

Displaying all 11 publications

Abstract:

Sort:

Modification to reporting of qualitative fluorescent spot test results improves detection of glucose-6-phosphate dehydrogenase (G6PD)-deficient heterozygote female newborns

Nadarajan V, Shanmugam H, Sthaneshwar P, Jayaranee S, Sultan KS, Ang C, et al.

Int J Lab Hematol, 2011 Oct;33(5):463-70.
PMID: 21501392 DOI: 10.1111/j.1751-553X.2011.01309.x

INTRODUCTION:
The glucose-6-phosphate dehydrogenase (G6PD) fluorescent spot test (FST) is a useful screening test for G6PD deficiency, but is unable to detect heterozygote G6PD-deficient females. We sought to identify whether reporting intermediate fluorescence in addition to absent and bright fluorescence on FST would improve identification of mildly deficient female heterozygotes.

METHODS:
A total of 1266 cord blood samples (705 male, 561 female) were screened for G6PD deficiency using FST (in-house method) and a quantitative enzyme assay. Fluorescence intensity of the FST was graded as either absent, intermediate or normal. Samples identified as showing absent or intermediate fluorescence on FST were analysed for the presence of G6PD mutations using TaqMan@SNP genotyping assays and direct nucleotide sequencing.

RESULTS:
Of the 1266 samples, 87 samples were found to be intermediate or deficient by FST (49 deficient, 38 intermediate). Of the 49 deficient samples, 48 had G6PD enzyme activity of ≤ 9.5 U/g Hb and one sample had normal enzyme activity. All 38 intermediate samples were from females. Of these, 21 had G6PD activity of between 20% and 60%, and 17 samples showed normal G6PD activity. Twenty-seven of the 38 samples were available for mutation analysis of which 13 had normal G6PD activity. Eleven of the 13 samples with normal G6PD activity had identifiable G6PD mutations.

CONCLUSION:
Glucose-6-phosphate dehydrogenase heterozygote females cannot be identified by FST if fluorescence is reported as absent or present. Distinguishing samples with intermediate fluorescence from absent and bright fluorescence improves detection of heterozygote females with mild G6PD deficiency. Mutational studies confirmed that 85% of intermediate samples with normal enzyme activity had identifiable G6PD mutations.

Matched MeSH terms: Glucosephosphate Dehydrogenase/metabolism
Biochemical characteristics of glucose-6-phosphate dehydrogenase variants among the Malays of Singapore with report of a new non-deficient (GdSingapore) and three deficient variants

Saha N, Hong SH, Wong HA, Jeyaseelan K, Tay JS

Jinrui Idengaku Zasshi, 1991 Dec;36(4):307-12.
PMID: 1811096 DOI: 10.1007/BF01883603

Biochemical characteristics of one non-deficient fast G6PD variant (GdSingapore) and six different deficient variants (three new, two Mahidol, one each of Indonesian and Mediterranean) were studied among the Malays of Singapore. The GdSingapore variant had normal enzyme activity (82%) and fast electrophoretic mobilities (140% in TEB buffer, 160% in phosphate and 140% in Tris-HCl buffer systems respectively). This variant is further characterized by normal Km for G6P; utilization of analogues (Gal6P, 2dG6P; dAmNADP), heat stability and pH optimum. The other six deficient G6PD variants had normal electrophoretic mobility in TEB buffer with enzyme activities ranging from 1 to 12% of GdB+. The biochemical characteristics identity them to be 2 Mahidol, 1 Indonesian and 1 Mediterranean variants and three new deficient variants.

Matched MeSH terms: Glucosephosphate Dehydrogenase/metabolism
Glucose-6-phosphate dehydrogenase enzyme activity in normal, hemizygote and heterozygote Kelantanese Malays

Normah J, Choo KE, Oppenheimer SJ, Selamah G

J Paediatr Child Health, 1991 Dec;27(6):376-9.
PMID: 1756082

This prospective study was performed to quantify glucose-6-phosphate dehydrogenase (G6PD) enzyme activity in deficient males and female heterozygotes. The methods used in the study were the fluorescent spot test, G6PD enzyme electrophoresis on cellulose acetate and quantitative assays. Forty-seven children who had been detected as spot screen deficient at birth were rescreened. Their first degree relatives were also included in the study. The mean enzyme activity of deficient males was 0.74 iu/g Hb (s.d. +/- 0.8), of female heterozygotes was 6.5 iu/g Hb (s.d. +/- 3.2) and of normal males was 12.1 iu/g Hb (s.d. +/- 3.5). The mean activity in deficient males was 6.1% of normal males. Most (35 of 47) of these fell into class 2 in Beutler's classification of G6PD variants. This indicates a population which may be susceptible to favism. Female heterozygotes had an intermediate enzyme activity with a wide scatter. Using a cut off point of enzyme activity of below 9.0 iu/g Hb gave sensitivity and specificity of 87% and 84% in detecting female heterozygotes. This group could be defined more accurately by combining quantitative assays with family studies.

Matched MeSH terms: Glucosephosphate Dehydrogenase/metabolism*
Glucose-6-phosphate dehydrogenase (G6PD) variants in Malaysian Chinese

Ainoon O, Joyce J, Boo NY, Cheong SK, Zainal ZA, Hamidah NH

Hum Mutat, 1999 Oct;14(4):352.
PMID: 10502785 DOI: 10.1002/(SICI)1098-1004(199910)14:4<352::AID-HUMU1

We screened 38 G6PD-deficient male Chinese neonates for known G6PD mutations using established PCR-based techniques. We found 50.0% (19 of 38) were mutation 1376G>T, 34.2% (13 of 38) were mutation 1388G>A, 5.2% (2 of 38 ) were mutation 95A>G and 2.2% (1 of 38) was mutation 1024C>T. In 7% (3 of 38) of the cases the mutations remained uncharacterised. Sixty three percent (24 of 38) of the G6PD deficient neonates had neonatal jaundice with 28.9 % (11 of 38) developing moderate to severe hyperbilirubinemia. The group of neonates with 1388 mutation showed the highest incidence of moderate to severe hyperbilirubinemia requiring phototherapy and/or exchange transfusion respectively. Majority (70%) of the G6PD deficient neonates showed severe enzyme deficiency. However, there was no meaningful association between the level of enzyme activity and the severity of neonatal jaundice. In summary, four mutations account for more than 90% of the G6PD deficiency cases among the Chinese in Malaysia and the pattern of distribution of the molecular variants is similar to those found among the Chinese in Taiwan and southern mainland China. Our findings also suggest the possible association of nt 1388 mutation with severe neonatal jaundice.

Matched MeSH terms: Glucosephosphate Dehydrogenase/metabolism
Glucose-6-phosphate dehydrogenase (G6PD) variants in Malaysian Malays

Ainoon O, Yu YH, Amir Muhriz AL, Boo NY, Cheong SK, Hamidah NH

Hum Mutat, 2003 Jan;21(1):101.
PMID: 12497642 DOI: 10.1002/humu.9103

We performed DNA analysis using cord blood samples on 86 male Malay neonates diagnosed as G6PD deficiency in the National University of Malaysia Hospital by a combination of rapid PCR-based techniques, single-stranded conformation polymorphism analysis (SSCP) and DNA sequencing. We found 37.2% were 871G>A (G6PD Viangchan), 26.7% were nt 563 C>T (G6PD Mediterranean) and 15.1% were 487G>A (G6PD Mahidol) followed by 4.7% 1376G>T (G6PD Canton), 3.5% 383T>C (G6PD Vanua Lava), 3.5% 592C>T (G6PD Coimbra), 2.3% 1388G>A (G6PD Kaiping), 2.3% 1360C>T (G6PD Union), 2.3% 1003G>A (G6PD Chatham), 1.2% 131C>G (G6PD Orissa) and 1.2% 1361G>A (G6PD Andalus). Seventy-one (82.6%) of the 86 G6PD-deficient neonates had neonatal jaundice. Fifty seven (80%) of the 71 neonates with jaundice required phototherapy with only one neonate progressing to severe hyperbilirubinemia (serum bilirubin >340 micromol/l) requiring exchange transfusion. There was no significant difference in the incidence of neonatal jaundice, mean serum bilirubin level, mean age for peak serum bilirubin, percentage of babies requiring phototherapy and mean number of days of phototherapy between the three common variants. In conclusion, the molecular defects of Malay G6PD deficiency is heterogeneous and G6PD Viangchan, Mahidol and Mediterranean account for at least 80% of the cases. Our findings support the observation that G6PD Viangchan and Mahidol are common Southeast Asian variants. Their presence in the Malays suggests a common ancestral origin with the Cambodians, Laotians and Thais. Our findings together with other preliminary data on the presence of the Mediterranean variant in this region provide evidence of strong Arab influence in the Malay Archipelago.

Matched MeSH terms: Glucosephosphate Dehydrogenase/metabolism
Homozygous state for Hb Constant Spring (slow-moving Hb X components)

Lie-Injo LE, Ganesan J, Clegg JB, Weatherall DJ

Blood, 1974 Feb;43(2):251-9.
PMID: 4810076
Matched MeSH terms: Glucosephosphate Dehydrogenase/metabolism
Distribution of glucose-6-phosphate dehydrogenase mutations in Southeast Asia

Iwai K, Hirono A, Matsuoka H, Kawamoto F, Horie T, Lin K, et al.

Hum Genet, 2001 Jun;108(6):445-9.
PMID: 11499668

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a heterogeneous enzyme abnormality with high frequency in tropical areas. We performed population screening and molecular studies of G6PD variants to clarify their distribution and features in Southeast Asia. A total of 4317 participants (2019 males, 2298 females) from 16 ethnic groups in Myanmar, Lao in Laos, and Amboinese in Indonesia were screened with a single-step screening method. The prevalence of G6PD-deficient males ranged from 0% (the Akha) to 10.8% (the Shan). These G6PD-deficient individuals and 12 G6PD-deficient patients who had been diagnosed at hospitals in Indonesia and Malaysia were subjected to molecular analysis by a combination of polymerase-chain-reaction-based single-strand conformation polymorphism analysis and direct sequencing. Ten different missense mutations were identified in 63 G6PD-deficient individuals (50 hemizygotes, 11 heterozygotes, and 2 homozygotes) from 14 ethnic groups. One missense mutation (1291 G-->A) found in an Indonesian Chinese, viz., G6PD Surabaya, was previously unknown. The 487 G-->A (G6PD Mahidol) mutation was widely seen in Myanmar, 383 T-->C (G6PD Vanua Lava) was specifically found among Amboinese, 871 G-->A (G6PD Viangchan) was observed mainly in Lao, and 592 C-->T (G6PD Coimbra) was found in Malaysian aborigines (Orang Asli). The other five mutations, 95 A-->G (G6PD Gaohe), 1003 G-->A (G6PD Chatham), 1360 C-->T (G6PD Union), 1376 G-->T (G6PD Canton), and 1388 G-->A (G6PD Kaiping) were identified mostly in accordance with distributions reported previously.

Matched MeSH terms: Glucosephosphate Dehydrogenase/metabolism
Genetic red cell abnormalities in Trengganu and Perlis (West Malaysia)

Eng LI, McKay DA, Govindasamy S

Southeast Asian J Trop Med Public Health, 1971 Jun;2(2):133-9.
PMID: 5002823
Matched MeSH terms: Glucosephosphate Dehydrogenase/metabolism
Genetic Factors and Delayed TSB Monitoring and Treatment as Risk Factors Associated with Severe Hyperbilirubinemia in Term Neonates Admitted for Phototherapy

Boo NY, Sin S, Chee SC, Mohamed M, Ahluwalia AK, Ling MM, et al.

J Trop Pediatr, 2020 12 01;66(6):569-582.
PMID: 32577754 DOI: 10.1093/tropej/fmaa016

OBJECTIVES: This study aimed to determine whether maternal-fetal blood group isoimmunization, breastfeeding, birth trauma, age when first total serum bilirubin (TSB) was measured, age of admission, and genetic predispositions to hemolysis [due to genetic variants of glucose-6-phosphate dehydrogenase (G6PD) enzyme], and reduced hepatic uptake and/or conjugation of serum bilirubin [due to genetic variants of solute carrier organic anion transporter protein family member 1B1 (SLCO1B1) and uridine diphosphate glucuronosyltransferase family 1 member A1 (UGT1A1)] were significant risk factors associated with severe neonatal hyperbilirubinemia (SNH, TSB ≥ 342µmol/l) in jaundiced term neonates admitted for phototherapy.
METHODS: The inclusion criteria were normal term neonates (gestation ≥ 37 weeks). Parents/care-givers were interviewed to obtain data on demography, clinical problems, feeding practice and age when first TSB was measured. Polymerase chain reaction-restriction fragment length polymorphism method was used to detect common G6PD, UGT1A1 and SLCO1B1 variants on each neonate's dry blood specimens.
RESULTS: Of 1121 jaundiced neonates recruited, 232 had SNH. Logistic regression analysis showed that age (in days) when first TSB was measured [adjusted odds ratio (aOR) = 1.395; 95% confidence interval (CI) 1.094-1.779], age (in days) of admission (aOR = 1.127; 95% CI 1.007-1.260) and genetic mutant UGT1A1 promoter A(TA)7TAA (aOR = 4.900; 95% CI 3.103-7.739), UGT1A1 c.686C>A (aOR = 6.095; 95% CI 1.549-23.985), SLCO1B1 c.388G>A (aOR = 1.807; 95% CI 1.242-2.629) and G6PD variants and/or abnormal G6PD screening test (aOR = 2.077; 95% CI 1.025-4.209) were significantly associated with SNH.
CONCLUSION: Genetic predisposition, and delayed measuring first TSB and commencing phototherapy increased risk of SNH.

Matched MeSH terms: Glucosephosphate Dehydrogenase/metabolism
Fulltext Vernonia amygdalina simultaneously suppresses gluconeogenesis and potentiates glucose oxidation via the pentose phosphate pathway in streptozotocin-induced diabetic rats

Atangwho IJ, Yin KB, Umar MI, Ahmad M, Asmawi MZ

BMC Complement Altern Med, 2014;14:426.
PMID: 25358757 DOI: 10.1186/1472-6882-14-426

This study evaluated the impact of Vernonia amygdalina (VA) on the transcription of key enzymes involved in cellular modulation of glucose in streptozotocin-induced diabetic rats in a bid to understand the possible anti-diabetic mechanism of VA.

Matched MeSH terms: Glucosephosphate Dehydrogenase/metabolism
Diazinon-induced oxidative stress and renal dysfunction in rats

Shah MD, Iqbal M

Food Chem Toxicol, 2010 Dec;48(12):3345-53.
PMID: 20828599 DOI: 10.1016/j.fct.2010.09.003

Diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphoro thioate), an organo-phosphate insecticide, has been used worldwide in agriculture and domestic for several years, which has led to a variety of negative effects in non target species including humans. However, its nephrotoxic effects and mechanism of action has not been fully elucidated so far. Therefore, the present study was aimed at evaluating the nephrotoxic effects of diazinon and its mechanism of action with special reference to its possible ROS generating potential in rats. Treatment of rats with diazinon significantly enhances renal lipid peroxidation which is accompanied by a decrease in the activities of renal antioxidant enzymes (e.g. catalase, glutathione peroxidise, glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione S-transferase) and depletion in the level of glutathione reduced. In contrast, the activities of renal γ-glutamyl transpeptidase and quinone reductase were increased. Parallel to these changes, diazinon treatment enhances renal damage as evidenced by sharp increase in blood urea nitrogen and serum creatinine. Additionally, the impairment of renal function corresponds histopathologically. In summary, our results indicate that diazinon treatment eventuates in decreased renal glutathione reduced, a fall in the activities of antioxidant enzymes including the enzymes involved in glutathione metabolism and excessive production of oxidants with concomitant renal damage, all of which are involved in the cascade of events leading to diazinon-mediated renal oxidative stress and toxicity. We concluded that in diazinon exposure, depletion of antioxidant enzymes is accompanied by induction of oxidative stress that might be beneficial in monitoring diazinon toxicity.

Matched MeSH terms: Glucosephosphate Dehydrogenase/metabolism