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Erythrocytic glucose-6-phosphate dehydrogenase (G6PD) deficiency

Wong HB

Family Practitioner, 1983;6:23-28.

Matched MeSH terms: Glucosephosphate Dehydrogenase Deficiency
Favism and glucose-6-phosphate dehydrogenase deficiency

Winterbourn CC, Cheah FC

N Engl J Med, 2018 03 15;378(11):1067-8.
PMID: 29542310 DOI: 10.1056/NEJMc1801271

Comment on: Luzzatto L, Arese P. Favism and Glucose-6-Phosphate Dehydrogenase Deficiency.
N Engl J Med. 2018 Jan 4;378(1):60-71. Review. PubMed PMID: 29298156.

Matched MeSH terms: Glucosephosphate Dehydrogenase Deficiency*
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/genetics*; Glucosephosphate Dehydrogenase/metabolism; Glucosephosphate Dehydrogenase Deficiency/diagnosis*; Glucosephosphate Dehydrogenase Deficiency/genetics*; Glucosephosphate Dehydrogenase Deficiency/metabolism
Glucose-6-phosphate dehydrogenase (G6PD)-deficient infants: Enzyme activity and gene variants as risk factors for phototherapy in the first week of life

Wong FL, Ithnin A, Othman A, Cheah FC

J Paediatr Child Health, 2017 Jul;53(7):705-710.
PMID: 28376293 DOI: 10.1111/jpc.13509

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.
Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia

Matched MeSH terms: Glucosephosphate Dehydrogenase Deficiency*
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/genetics*; Glucosephosphate Dehydrogenase/metabolism; Glucosephosphate Dehydrogenase Deficiency/enzymology; Glucosephosphate Dehydrogenase Deficiency/genetics*
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/genetics; Glucosephosphate Dehydrogenase/metabolism*; Glucosephosphate Dehydrogenase Deficiency/enzymology; Glucosephosphate Dehydrogenase Deficiency/genetics*
Nine different glucose-6-phosphate dehydrogenase (G6PD) variants in a Malaysian population with Malay, Chinese, Indian and Orang Asli (aboriginal Malaysian) backgrounds

Wang J, Luo E, Hirai M, Arai M, Abdul-Manan E, Mohamed-Isa Z, et al.

Acta Med Okayama, 2008 Oct;62(5):327-32.
PMID: 18985093

The Malaysian people consist of several ethnic groups including the Malay, the Chinese, the Indian and the Orang Asli (aboriginal Malaysians). We collected blood samples from outpatients of 2 hospitals in the State of Selangor and identified 27 glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects among these ethnic groups. In the Malay, G6PD Viangchan (871GA, 1311CT, IVS11 nt93TC) and G6PD Mahidol (487GA) types, which are common in Cambodia and Myanmar, respectively, were detected. The Malay also had both subtypes of G6PD Mediterranean:the Mediterranean subtype (563CT, 1311CT, IVS11 nt93TC) and the Indo-Pakistan subtype (563CT, 1311C, IVS11 nt93T). In Malaysians of Chinese background, G6PD Kaiping (1388GA), G6PD Canton (1376GT) and G6PD Gaohe (95AG), which are common in China, were detected. Indian Malaysians possessed G6PD Mediterranean (Indo-Pakistan subtype) and G6PD Namoru (208TC), a few cases of which had been reported in Vanuatu and many in India. Our findings indicate that G6PD Namoru occurs in India and flows to Malaysia up to Vanuatu. We also discovered 5 G6PD-deficient cases with 2 nucleotide substitutions of 1311CT and IVS11 nt93TC, but without amino-acid substitution in the G6PD molecule. These results indicate that the Malaysian people have incorporated many ancestors in terms of G6PD variants.

Matched MeSH terms: Glucosephosphate Dehydrogenase/genetics*; Glucosephosphate Dehydrogenase Deficiency/blood; Glucosephosphate Dehydrogenase Deficiency/ethnology; Glucosephosphate Dehydrogenase Deficiency/genetics*
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/genetics*; Glucosephosphate Dehydrogenase/metabolism; Glucosephosphate Dehydrogenase Deficiency/diagnosis; Glucosephosphate Dehydrogenase Deficiency/ethnology; Glucosephosphate Dehydrogenase Deficiency/genetics*
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/genetics*; Glucosephosphate Dehydrogenase/metabolism; Glucosephosphate Dehydrogenase Deficiency/enzymology; Glucosephosphate Dehydrogenase Deficiency/genetics*; Glucosephosphate Dehydrogenase Deficiency/epidemiology
Mediterranean glucose-6-phosphate dehydrogenase (G6PD(C563T)) mutation among Jordanian females with acute hemolytic crisis

Al-Alimi AA, Kanakiri N, Kamil M, Al-Rimawi HS, Zaki AH, Yusoff NM

J Coll Physicians Surg Pak, 2010 Dec;20(12):794-7.
PMID: 21205543 DOI: 12.2010/JCPSP.794797

OBJECTIVE:
To evaluate the G6PD(C563T) Mediterranean mutation among Jordanian females who were admitted to Princess Rahma Teaching Hospital (PRTH) with/or previous history of favism.
STUDY DESIGN:
A descriptive study.
PLACE AND DURATION OF STUDY:
Jordanian University of Science and Technology and PRTH, from October 2003 to October 2004.
METHODOLOGY:
After obtaining approval from the Ethics Committee of Jordanian University of Science and Technology, a total of 32 females were included in this study. Samples from 15 healthy individual females were used as a negative control. Blood samples from these patients were collected and analyzed by allele-specific polymerase chain reaction (AS-PCR) to determine the G6PD(C563T) mutation.
RESULTS:
Twenty one out of 32 patients were found to be G6PD(C563T) Mediterranean mutation (65.6%) positive. Three out of 21 patients were homozygous and remaining 18 were heterozygous for G6PD(C563T) Mediterranean mutation. Eleven (34.4%) out of 32 patients were found to be negative for G6PD(C563T) mutation indicating the presence of other G6PD mutations in the study sample.
CONCLUSION:
G6PD(C563T) Mediterranean mutation accounted for 65.6% of the study sample with favism in the North of Jordan. There is likely to be another G6PD deficiency variant implicated in acute hemolytic crisis (favism).

Matched MeSH terms: Glucosephosphate Dehydrogenase/genetics*; Glucosephosphate Dehydrogenase Deficiency/complications; Glucosephosphate Dehydrogenase Deficiency/genetics*
Genotyping of Malaysian G6PD-deficient neonates by reverse dot blot flow-through hybridisation

Alina MF, Azma RZ, Norunaluwar J, Azlin I, Darnina AJ, Cheah FC, et al.

J Hum Genet, 2020 Mar;65(3):263-270.
PMID: 31863082 DOI: 10.1038/s10038-019-0700-7

G6PD deficiency is the commonest enzyme deficiency found in humans. Current diagnostic methods lack sensitivity to detect all cases of G6PD deficiency. We evaluated the reverse dot blot flow-through hybridisation assay designed to detect simultaneously multiple known G6PD mutations in a group of Malaysian neonates. Archival DNA samples from 141 G6PD-deficient neonates were subjected to reverse dot blot flow-through hybridisation assay using the GenoArray Diagnostic Kit (Hybribio Limited, Hong Kong) and DNA sequencing. The method involved PCR amplification of 5 G6PD exons using biotinylated primers, hybridisation of amplicons to a membrane containing oligoprobes designed for G6PD mutations known to occur in the Malaysian population and colour detection by enzyme immunoassay. The assay detected 13 of the 14 G6PD mutations and genotyped 133 (94.3%) out of 141 (102 males, 39 females) cases. Among the 39 female G6PD-deficient neonates, there were 7 homozygous and 6 compound heterozygous cases. The commonest alleles were G6PD Viangchan 871G > A (21%) and G6PD Mahidol 487G > A(20%) followed by G6PD Mediterranean 563C > T, (14%), G6PD Vanua Lava 383T > C (12%), G6PD Canton 1376G > T (10%), G6PD Orissa 131C > G (6.3%) G6PD Coimbra 592C > T (5.6%) plus 6 other mutations. DNA sequencing of remaining cases revealed 6 cases of intron 11 nt 93C > T not previously reported in Malaysia and two novel mutations, one case each of nt 1361G > T and nt 1030G > A. We found the reverse dot blot assay easy to perform, rapid, accurate and reproducible, potentially becoming an improved diagnostic test for G6PD deficiency.

Matched MeSH terms: Glucosephosphate Dehydrogenase/genetics*; Glucosephosphate Dehydrogenase Deficiency/genetics*; Glucosephosphate Dehydrogenase Deficiency/pathology
Fulltext Genetic analysis and molecular basis of G6PD deficiency among malaria patients in Thailand: implications for safe use of 8-aminoquinolines

Boonyuen U, Jacob BAC, Wongwigkan J, Chamchoy K, Singha-Art N, Pengsuk N, et al.

Malar J, 2024 Feb 02;23(1):38.
PMID: 38308253 DOI: 10.1186/s12936-024-04864-8

BACKGROUND: It was hypothesized that glucose-6-phosphate dehydrogenase (G6PD) deficiency confers a protective effect against malaria infection, however, safety concerns have been raised regarding haemolytic toxicity caused by radical cure with 8-aminoquinolines in G6PD-deficient individuals. Malaria elimination and control are also complicated by the high prevalence of G6PD deficiency in malaria-endemic areas. Hence, accurate identification of G6PD deficiency is required to identify those who are eligible for malaria treatment using 8-aminoquinolines.
METHODS: The prevalence of G6PD deficiency among 408 Thai participants diagnosed with malaria by microscopy (71), and malaria-negative controls (337), was assessed using a phenotypic test based on water-soluble tetrazolium salts. High-resolution melting (HRM) curve analysis was developed from a previous study to enable the detection of 15 common missense, synonymous and intronic G6PD mutations in Asian populations. The identified mutations were subjected to biochemical and structural characterisation to understand the molecular mechanisms underlying enzyme deficiency.
RESULTS: Based on phenotypic testing, the prevalence of G6PD deficiency (T) and intronic (c.1365-13T>C and c.486-34delT) mutations was detected with intermediate to normal enzyme activity. The double missense mutations were less catalytically active than their corresponding single missense mutations, resulting in severe enzyme deficiency. While the mutations had a minor effect on binding affinity, structural instability was a key contributor to the enzyme deficiency observed in G6PD-deficient individuals.
CONCLUSIONS: With varying degrees of enzyme deficiency, G6PD genotyping can be used as a complement to phenotypic screening to identify those who are eligible for 8-aminoquinolines. The information gained from this study could be useful for management and treatment of malaria, as well as for the prevention of unanticipated reactions to certain medications and foods in the studied population.

Matched MeSH terms: Glucosephosphate Dehydrogenase/analysis; Glucosephosphate Dehydrogenase/genetics
G6PD deficiency with hemolytic anemia due to a rare gene deletion--a report of the first case in Malaysia

Ainoon O, Boo NY, Yu YH, Cheong SK, Hamidah HN

Hematology, 2006 Apr;11(2):113-8.
PMID: 16753852 DOI: 10.1080/10245330500155184

A 2-year-old Chinese boy was referred to Hospital UKM for investigation of recurrent episodes of dark-coloured urine and pallor since birth. He was born prematurely at 34 weeks gestation and developed severe early-onset neonatal jaundice requiring exchange blood transfusion. Screening at birth showed Glucose-6-phosphate dehydrogenase (G6PD) deficiency. On admission, physical examination revealed pallor, jaundice and mild hepatomegaly. Results of laboratory investigations showed a hemoglobin level of 11.0 g/dl with a hemolytic blood picture, reticulocytosis of 20% and red cell G6PD activity reported as undetectable. The patient's DNA was analysed for G6PD mutations by PCR-based techniques and DNA sequencing and results showed a 24 bp deletion of nucleotide 953-976 in the exon 9 of the G6PD gene. DNA analysis was also performed on blood samples of the patient's mother and female sibling confirming their heterozygous status, although both showed normal red cell G6PD activity levels. The patient was discharged well and his parents were appropriately advised on the condition and the importance of taking folic acid regularly. This is a first case report in Malaysia of G6PD deficiency causing chronic-hemolytic anemia. The rare 24 bp deletion causes the G6PD Nara variant, previously reported only in two other unrelated males, a Japanese and a Portuguese both with chronic hemolytic anemia.

Matched MeSH terms: Glucosephosphate Dehydrogenase/genetics; Glucosephosphate Dehydrogenase Deficiency/diagnosis; Glucosephosphate Dehydrogenase Deficiency/genetics*; Glucosephosphate Dehydrogenase Deficiency/epidemiology
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/genetics*; Glucosephosphate Dehydrogenase/metabolism; Glucosephosphate Dehydrogenase Deficiency/genetics*; Glucosephosphate Dehydrogenase Deficiency/epidemiology
Prevalence and molecular study of G6PD deficiency in Malaysian Orang Asli

Amini F, Ismail E, Zilfalil BA

Intern Med J, 2011 Apr;41(4):351-3.
PMID: 21507164 DOI: 10.1111/j.1445-5994.2011.02456.x

This study aims to define the prevalence and the molecular basis of G6PD deficiency in the Negrito tribe of the Malaysian Orang Asli. Four hundred and eighty seven consenting Negrito volunteers were screened for G6PD deficiency through the use of a fluorescent spot test. DNA from deficient individuals underwent PCR-RFLP analysis using thirteen recognized G6PD mutations. In the instances when the mutation could not be identified by PCR-RFLP, the entire coding region of the G6PD gene was subjected to DNA sequencing. In total, 9% (44/486) of the sample were found to be G6PD-deficient. However, only 25 samples were subjected to PCR-RFLP and DNA sequencing. Of these, three were found to carry Viangchan, one Coimbra and 16, a combination of C1311T in exon 11 and IVS11 T93C. Mutation(s) for the five remaining samples are unknown. The mean G6PD enzyme activity ranged 5.7 IU/gHb in deficient individuals. Our results demonstrate that the frequency of G6PD deficiency is higher among the Negrito Orang Asli than other Malaysian races. The dual presence of C1311T and IVS11 T93C in 64% of the deficient individuals (16/44) could well be a result of genetic drift within this isolated group.

Matched MeSH terms: Glucosephosphate Dehydrogenase/genetics*; Glucosephosphate Dehydrogenase Deficiency/ethnology*; Glucosephosphate Dehydrogenase Deficiency/genetics*; Glucosephosphate Dehydrogenase Deficiency/epidemiology
Fulltext A freeze-dried method for preparation of G6PD reagent tubes

Cheong SK, Lim YC, Mok KL

Malays J Pathol, 1991 Jun;13(1):51-2.
PMID: 1795563

Mixed reagents for the Glucose-6-phosphate dehydrogenase (G6PD) deficiency fluorescent screening test were freeze-dried in plastic tubes. The reagents were then reconstituted with distilled water and the test was performed in the usual way. Initial testing with the freeze-dried mixed reagents gave consistent positive reaction to 12 normal blood samples and negative reaction to 9 G6PD deficient blood samples. This will enable a laboratory with freeze-drying facilities to prepare reagent tubes in bulk. As these tubes can be kept at 4 degrees C and do not require to be stored at -20 degrees C, a major laboratory can prepare these tubes and supply small laboratories for screening purposes.

Matched MeSH terms: Glucosephosphate Dehydrogenase Deficiency/diagnosis*
Screening for G. 6-P.D. deficiency

Robinson MJ, Lau KS, Lin HP, Chan GL

Med J Malaysia, 1976 Jun;30(4):287-90.
PMID: 979730
Matched MeSH terms: Glucosephosphate Dehydrogenase Deficiency/diagnosis*
Glucose-6-phosphate dehydrogenase deficiency in Brunei, Sabah and Sarawak

Lie-Injo LE, Chin J, Ti TS

Ann. Hum. Genet., 1964 Nov;28:173-6.
PMID: 14228004 DOI: 10.1111/j.1469-1809.1964.tb00472.x

A total of 1008 healthy unrelated young adult male police and military recruits, 317 from Brunei, 398 from Sabah and 293 from Sarawak, were examined for G-6-PD deficiency. The frequency in the 317 Brunei recruits, who were all of Malay origin, was 6.3 %. In Sabah the frequencies for the four main ethnic groups were 12.1 % in 165 Kadazans, 4.1% in 73 Malays, 3.4 % in 68 Bajaus and 24.2 % in 33 Muruts. In Sarawak the frequency was 11.6 % in 95 recruits of Malay origin. Three among 56 Ibans and one among 80 Sea Dayaks were found to be enzyme-deficient, but the numbers examined of these groups were too small for estimation of the frequency. The overall frequency for the Malay group in Brunei, Sabah and Sarawak was 7.0% in 485 persons examined.

Matched MeSH terms: Glucosephosphate Dehydrogenase Deficiency*
3'-UTR variations and G6PD deficiency

Amini F, Ismail E

J Hum Genet, 2013 Apr;58(4):189-94.
PMID: 23389243 DOI: 10.1038/jhg.2012.155

The combination of two silent mutations, c.1311C>T in exon 11 and IVS11 T93C (glucose-6-phosphate dehydrogenase (G6PD) 1311T/93C), with unknown mechanism, have been reported in G6PD-deficient individuals in Asian populations including Malaysian aboriginal group, Negrito. Here, we report the screening of G6PD gene in 103 Negrito volunteers using denaturing high-performance liquid chromatography (dHPLC) and direct sequencing. A total of 48 individuals (46.6%) were G6PD deficient, 83.3% of these carried G6PD 1311T/93C with enzyme activity ranging from 1.8 to 4.8 U gHb(-1). Three novel single-nucleotide polymorphisms (SNPs), rs112950723, rs111485003 and rs1050757, were found in the G6PD 3'-untranslated region (UTR). Strong association was observed between haplotype 1311T/93C and rs1050757G, which is located inside the 35 bp AG-rich region. In silico analysis revealed that the transition of A to G at position rs1050757 makes significant changes in the G6PD mRNA secondary structure. Moreover, putative micro (mi)RNA target sites were identified in 3'-UTR of G6PD gene, two of these in the region encompassing rs1050757. It could be speculated that rs1050757 have a potential functional effect on the downregulation of mRNA and consequently G6PD deficiency either by affecting mRNA stability and translation or mirRNA regulation process. This is the first report of biochemical association of an SNP in 3'-UTR of G6PD gene and the possible role of mRNA secondary structure.

Matched MeSH terms: Glucosephosphate Dehydrogenase/genetics*; Glucosephosphate Dehydrogenase Deficiency/genetics*
Fulltext The challenges of introducing routine G6PD testing into radical cure: a workshop report

Ley B, Luter N, Espino FE, Devine A, Kalnoky M, Lubell Y, et al.

Malar J, 2015 Sep 29;14:377.
PMID: 26416229 DOI: 10.1186/s12936-015-0896-8

The only currently available drug that effectively removes malaria hypnozoites from the human host is primaquine. The use of 8-aminoquinolines is hampered by haemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Recently a number of qualitative and a quantitative rapid diagnostic test (RDT) format have been developed that provide an alternative to the current standard G6PD activity assays. The WHO has recently recommended routine testing of G6PD status prior to primaquine radical cure whenever possible. A workshop was held in the Philippines in early 2015 to discuss key challenges and knowledge gaps that hinder the introduction of routine G6PD testing. Two point-of-care (PoC) test formats for the measurement of G6PD activity are currently available: qualitative tests comparable to malaria RDT as well as biosensors that provide a quantitative reading. Qualitative G6PD PoC tests provide a binomial test result, are easy to use and some products are comparable in price to the widely used fluorescent spot test. Qualitative test results can accurately classify hemizygous males, heterozygous females, but may misclassify females with intermediate G6PD activity. Biosensors provide a more complex quantitative readout and are better suited to identify heterozygous females. While associated with higher costs per sample tested biosensors have the potential for broader use in other scenarios where knowledge of G6PD activity is relevant as well. The introduction of routine G6PD testing is associated with additional costs on top of routine treatment that will vary by setting and will need to be assessed prior to test introduction. Reliable G6PD PoC tests have the potential to play an essential role in future malaria elimination programmes, however require an improved understanding on how to best integrate routine G6PD testing into different health settings.

Matched MeSH terms: Glucosephosphate Dehydrogenase/genetics*; Glucosephosphate Dehydrogenase Deficiency/diagnosis*

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