The 1985 version of WHO G6PD variation classification is no longer suitable for the development of modern medicine, and it has been revised by the WHO G6PD Technical Advisory Group. According to the genetic variation classification of G6PD by WHO in 2024, G6PD deficiency is divided into four categories: Class A: enzyme activity < 20% with chronic hemolytic anemia; Class B: enzyme activity < 45% in association with acute hemolysis caused by inducement; Class C: enzyme activity > 60%, no hemolysis; Class U: for those with incomplete clinical phenotypic information, and will be classified again with new clinical evidence obtained. The clinical implications of the new classification include: (1) To guide the prevention and treatment of G6PD deficiency; (2) To better understand the pathological and non-pathological status of G6PD deficiency, which lays a foundation for re-determining the birth defect rate in China; (3) To guide the safe use of anti-malarial drugs and related oxidizing drugs in G6PD deficient patients; (4) To promote the hierarchical health management of G6PD deficient individuals throughout their life cycle; (5) To guide the pathogenicity rating of G6PD gene variation; (6) To unify the diagnostic criteria for global G6PD deficiency, promote the homogenization, comparability and data sharing of global relevant data, and lay the foundation for the application of artificial intelligence.
Humans ; Glucosephosphate Dehydrogenase Deficiency/diagnosis* ; Glucosephosphate Dehydrogenase/genetics* ; Genetic Variation ; World Health Organization ; China

OBJECTIVE: To determine the incidence and genotypes of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Dongguan region of Guangdong Province and assess the efficacy and feasibility of flow-through hybridization. METHODS: Peripheral blood samples were randomly selected and detected by modified G6PD/6PGD ratio method. Flow-through hybridization was used to detect 14 G6PD mutations among all samples. RESULTS: In total 1005 samples were collected, the detection rate for modified G6PD/6PGD ratio method and flow-through hybridization were 2.79% and 20.90%, respectively. The consistency of the two methods was poor(Kappa=0.187). When c.1311C>T mutation is excluded, the consistency of the two methods was good for males (Kappa=0.952) but still poor for females (Kappa=0.194). The most common mutations were c.1376G>T, c.1388G>A and c.95A>G. No G6PD deficiency was found among those only carrying the c.1311C>T mutation. CONCLUSION Flow-through hybridization can simultaneously detect 14 loci, covering over 90% of common mutations in Chinese population, and can be easily expanded. The routine method may miss many females carrying homozygous, compound heterozygous and heterozygous mutations, but the detection rate for male hemizygous mutation was much higher.
China ; DNA Mutational Analysis ; Female ; Genetic Testing ; Genotype ; Glucosephosphate Dehydrogenase ; genetics ; Glucosephosphate Dehydrogenase Deficiency ; diagnosis ; Humans ; Male ; Mutation

OBJECTIVESince glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary hemolytic erythrocyte enzyme deficiency, most cases have single nucleotide mutations in the coding region, and current test methods for gene mutation have some missed detections, this study aimed to investigate the feasibility of RT-PCR sequencing in the detection of gene mutation in G6PD deficiency.

METHODSAccording to the G6PD/6GPD ratio, 195 children with anemia of unknown cause or who underwent physical examination between August 2013 and July 2014 were classified into G6PD-deficiency group with 130 children (G6PD/6GPD ratio <1.00) and control group with 65 children (G6PD/6GPD ratio≥1.00). The primer design and PCR amplification conditions were optimized, and RT-PCR sequencing was used to analyze the complete coding sequence and verify the genomic DNA sequence in the two groups.

RESULTSIn the G6PD-deficiency group, the detection rate of gene mutation was 100% and 13 missense mutations were detected, including one new mutation. In the control group, no missense mutation was detected in 28 boys; 13 heterozygous missense mutations, 1 homozygous same-sense mutation (C1191T) which had not been reported in China and abroad, and 14 single nucleotide polymorphisms of C1311T were detected in 37 girls. The control group showed a high rate of missed detection of G6PD deficiency (carriers) in the specimens from girls (35%, 13/37).

CONCLUSIONSRT-PCR sequencing has a high detection rate of G6PD gene mutation and a certain value in clinical diagnosis of G6PD deficiency.

Adolescent ; Child ; Child, Preschool ; Female ; Glucosephosphate Dehydrogenase ; genetics ; Glucosephosphate Dehydrogenase Deficiency ; diagnosis ; genetics ; Humans ; Infant ; Male ; Mutation ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Sequence Analysis, DNA

A 23-year-old man presented with abdominal pain after suffering blunt trauma caused by a seatbelt injury. His low platelet count of 137 × 10(9)/L was initially attributed to trauma and his underlying hypersplenism due to glucose-6-phosphate dehydrogenase (G6PD) deficiency. Despite conservative management, his platelet count remained persistently reduced even after his haemoglobin and clotting abnormalities were stabilised. After a week, follow-up imaging revealed an incidental finding of a pseudoaneurysm (measuring 9 mm × 8 mm × 10 mm) adjacent to a splenic laceration. The pseudoaneurysm was successfully closed via transcatheter glue embolisation; 20% of the spleen was also embolised. A week later, the platelet count normalised, and the patient was subsequently discharged. This case highlights the pitfalls in the detection of a delayed occurrence of splenic artery pseudoaneurysm after blunt injury via routine delayed phase computed tomography. While splenomegaly in G6PD may be a predisposing factor for injury, a low platelet count should arouse suspicion of internal haemorrhage rather than hypersplenism.
Abdominal Pain ; diagnosis ; etiology ; Accidents, Traffic ; Aneurysm, False ; diagnostic imaging ; etiology ; therapy ; Embolization, Therapeutic ; methods ; Follow-Up Studies ; Glucosephosphate Dehydrogenase Deficiency ; complications ; diagnosis ; Humans ; Injury Severity Score ; Male ; Rare Diseases ; Risk Assessment ; Seat Belts ; adverse effects ; Splenic Artery ; injuries ; Tomography, X-Ray Computed ; methods ; Treatment Outcome ; Wounds, Nonpenetrating ; complications ; diagnosis ; Young Adult

OBJECTIVETo study the feasibility of genetic diagnosis for female carriers of human glucose-6-phosphate dehydrogenase (G6PD) deficiency by reverse transcriptase-PCR-denaturing gradient gel electrophoresis (RT-PCR-DGGE).

METHODSBlood samples were collected from suspected 54 female carriers of G6PD deficiency. Total RNAs of peripheral blood were prepared and reverse-transcripted into cDNA. Design of 6 primer pairs for DGGE was based on 17 mutation sites of G6PD cDNA described in the Chinese population. Mutations in the coding region of G6PD gene were screened and genotyped by combination of PCR-DGGE and DNA sequencing.

RESULTSOne case of 1024C/T, 20 cases of 1376G/T and 12 cases of 1388G/A were detected in the 54 samples. The total detection rate was 66.1% (33/54).

CONCLUSIONSHeterozygous mutation rate in female carriers of G6PD deficiency detected by RT-PCR-DGGE is high. RT-PCR-DGGE is value of clinical diagnosis for G6PD-deficiency female carriers.

Adolescent ; Adult ; Child ; Child, Preschool ; Electrophoresis, Polyacrylamide Gel ; Female ; Glucosephosphate Dehydrogenase Deficiency ; diagnosis ; genetics ; Heterozygote ; Humans ; Infant ; Reverse Transcriptase Polymerase Chain Reaction ; methods

OBJECTIVETo develop a new stable and efficient reagent for methemoglobin reduction test.

METHODSThe results of methemoglobin reduction test using the new reagent were compared with those by G6P/6PG ratio method and classic methemoglobin reduction test.

RESULTSThe new reagent was stable for at least 6 months at room temperature and 12 months at 2-8 degrees celsius;. The results of the test using this new reagent were stable and reliable.

CONCLUSIONThe new reagent for methemoglobin reduction test allows easy operation with well reproducible results and can be used in clinical screening of glucose-6-phosphate dehydrogenase deficiency.

Glucosephosphate Dehydrogenase ; analysis ; Glucosephosphate Dehydrogenase Deficiency ; diagnosis ; Humans ; Mass Screening ; Methemoglobin ; metabolism ; Oxidation-Reduction ; Reagent Kits, Diagnostic ; Reproducibility of Results

INTRODUCTIONThe nationwide neonatal screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency in Taiwan was started on 1 July 1987. A network of G6PD referral hospitals distributed all around Taiwan was organised for follow-up, confirmatory testing, medical care and genetic counselling. To assess the reliability of confirmatory and screening tests, an external quality assurance (QA) programme for G6PD assay was developed.

MATERIALS AND METHODSLyophilised quality control (QC) materials and dried blood spots were prepared from erythrocytes and whole blood for confirmatory and screening tests, respectively. The external QA surveys were carried out every 1 to 2 months. The QA results were evaluated and compared to the consensus result and reference value. The test results were submitted through internet by participating laboratories and the summary reports were published on a webpage (http:// www.g6pd.tw) within 2 weeks.

RESULTSTwenty-one referral laboratories in Taiwan and 16 screening laboratories in Germany, Lebanon, Mainland China, Philippines, Thailand, Taiwan, Turkey, and Vietnam have been participating in the QA programme. From 1988 to 2007, 144 QA surveys for confirmatory testing were sent to referral laboratories. Among the 2,622 reports received, 292 (11.1%) were found to be abnormal. Interlaboratory coefficient of variation (CV) for the confirmatory test has reached below 10% in recent years. The significant improvement in interlaboratory CV was found to be correlated with the preventive site visits to the referral laboratories since November 2004. From 1999 to 2007, 52 external QA surveys for the screening test were performed. Among 504 reports received, 97 (19.2%) were found to be abnormal. From the 5040 blood spots tested by the screening laboratories, 95 false negative (1.9%) and 187 false positive (3.7%) results were reported.

CONCLUSIONSThe external QA programme has been useful for monitoring the performance of the referral hospitals and screening laboratories and helpful for the participating laboratories to improve their test quality.

Glucosephosphate Dehydrogenase Deficiency ; diagnosis ; Humans ; Infant, Newborn ; Neonatal Screening ; standards ; Quality Assurance, Health Care

INTRODUCTIONThis study aims to compare and assess usefulness of day 3 and 4 (49 to 96 hours) pre-phototherapy total serum bilirubin (TSB) in predicting subsequent significant hyperbilirubinaemia (SHB) in glucose-6-phosphate dehydrogenase (G6PD) deficient neonates.

MATERIALS AND METHODSThis prospective study was on all the G6PD deficient newborns weighing >2500 g. Day 3 and 4 pre-phototherapy TSB and phototherapy requirements in their first 2 weeks of life were analysed for its value in predicting subsequent SHB.

RESULTSThe frequency of G6PD deficiency was 2.4%, 1 per 42 live births (1.3% in males and 1.1% in females). Phototherapy was required in 51% of G6PD deficient infants, all within the first week of life. In the absence of SHB in the first week, the probability of its development in the second week was zero (95% confidence interval, 0 to 0.051). The day 4 pre-phototherapy TSB of <160 micromol/L predicted no measurable risk of subsequent SHB (sensitivity, 94%; 95% confidence interval, 83.5% to 97.9%; specificity 82.8%; 95% confidence interval, 71.1% to 90.4%).

CONCLUSIONSG6PD deficient newborns without SHB in their first week of life were at no measurable risk of its development in the second week. Day 4 pre-phototherapy has better sensitivity and specificity compared to day 3 pre-phototherapy TSB in predicting the risk of subsequent SHB. Low-risk infants, thus identified, may be eligible for discharge on or before day 7 of life. Infants with Day 4 TSB <160 can be even discharge on day 4 with follow-up appointment. Evidence-based early discharge can decrease the social, emotional and financial burden of G6PD deficiency in Singapore.

Bilirubin ; blood ; Female ; Glucosephosphate Dehydrogenase ; Glucosephosphate Dehydrogenase Deficiency ; diagnosis ; economics ; psychology ; Humans ; Hyperbilirubinemia, Neonatal ; diagnosis ; etiology ; prevention & control ; Infant, Newborn ; Jaundice, Neonatal ; Male ; Patient Discharge ; Phototherapy ; Prognosis ; Prospective Studies ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome

Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder worldwide, it has rarely been reported among Korean. The patient was previously healthy 39 yr old male who showed severe hemolytic anemia and acute renal failure accompanied by hyperbilirubinemia after hepatitis A infection. The additional studies for differential diagnosis of hemolytic anemia showed a moderate deficiency of G6PD enzyme. Because hepatitis A infection in patient with G6PD deficiency present much more severe clinical symptoms, G6PD enzyme should be examined in patients with triggering factors of hemolysis such as hepatitis A infection.
Adult ; Diagnosis, Differential ; Glucosephosphate Dehydrogenase/genetics ; Glucosephosphate Dehydrogenase Deficiency/*complications/diagnosis ; *Hemolysis ; Hepatitis A/*complications/diagnosis ; Hepatitis A Virus, Human/isolation & purification ; Humans ; Hyperbilirubinemia/etiology ; Kidney Failure, Acute/*diagnosis/etiology ; Male

OBJECTIVETo detect gene mutations of children with glucose-6-phosphorate dehydrogenase (G-6-PD) deficiency and of carriers of G-6-PD deficiency gene with the technique of polymerase chain reaction and denatured gradient gel electrophoresis (PCR-DGGE), and to explore the value of the technique in the diagnosis of G-6-PD deficiency and G-6-PD deficiency gene carrying.

METHODScDNAs were harvested by reverse transcription method after RNAs had been extracted from peripheral blood of 43 children with G-6-PD deficiency and of their family members (36 lineages). Electrophoresis behaviors of the fragment from exons 11-12 of G-6-PD cDNA were detected with the technique of PCR-DGGE. Gene sequencing was then performed for the abnormal electrophoresis bands.

RESULTSAbnormal electrophoresis bands were found in the 1304-1520 fragment of G-6-PD cDNA in 33 out of 36 family lineages. The G-6-PD/6-PGD ratio was below 1.00 in 9 mothers of patients. Three of them had the G-6-PD/6-PGD ratio lower than 0.50. The PCR-DGGE bands were the same in the 3 mothers. Gene sequencing showed double heterozygote in the 3 mothers, but the maternal carriers of G-6-PD deficiency gene who had normal G-6-PD/6-PGD ratio showed mono-heterozygote in gene sequencing. Three mutational sites were found in the 1304-1520 fragment, i.e., C1311TG1376T and G1388A. The electrophoresis behaviors were different among the 3 gene mutational sites.

CONCLUSIONSPCR-DGGE is a sensitive and reliable technique in the screening of gene mutations. It is useful in the diagnosis of G-6-PD deficiency, especially in the diagnosis of female G-6-PD deficiency gene carrying.

Base Sequence ; Electrophoresis, Polyacrylamide Gel ; Female ; Glucosephosphate Dehydrogenase Deficiency ; diagnosis ; genetics ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; methods ; Sequence Analysis, DNA