Contextual factors and G6PD diagnostic testing: a scoping review and evidence and gap map.

BACKGROUND: Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency is an important consideration regarding treatment for malaria. G6PD deficiency may lead to haemolytic anaemia during malaria treatment and, therefore, determining G6PD deficiency in malaria treatment strategies is extremely important. METHODS: This report presents the results of a scoping review and evidence and gap map for consideration by the Guideline Development Group for G6PD near patient tests to support radical cure of Plasmodium vivax. This scoping review has investigated common diagnostic tests for G6PD deficiency and important contextual and additional factors for decision-making. These factors include six of the considerations recommended by the World Health Organization (WHO) handbook for guideline development as important to determining the direction and strength of a recommendation, and included 'acceptability', 'feasibility,' 'equity,' 'valuation of outcomes,' 'gender' and 'human rights'. The aim of this scoping review is to inform the direction of future systematic reviews and evidence syntheses, which can then better inform the development of WHO recommendations regarding the use of G6PD deficiency testing as part of malaria treatment strategies. RESULTS: A comprehensive search was performed, including published, peer-reviewed literature for any article, of any study design and methodology that investigated G6PD diagnostic tests and the factors of 'acceptability', 'feasibility,' 'equity,' 'valuation of outcomes,' 'gender' and 'human rights'. There were 1152 studies identified from the search, of which 14 were determined to be eligible for inclusion into this review. The studies contained data from over 21 unique countries that had considered G6PD diagnostic testing as part of a malaria treatment strategy. The relationship between contextual and additional factors, diagnostic tests for G6PD deficiency and study methodology is presented in an overall evidence and gap, which showed that majority of the evidence was for the contextual factors for diagnostic tests, and the 'Standard G6PD (SD Biosensor)' test. CONCLUSIONS: This scoping review has produced a dynamic evidence and gap map that is reactive to emerging evidence within the field of G6PD diagnostic testing. The evidence and gap map has provided a comprehensive depiction of all the available literature that address the contextual and additional factors important for decision-making, regarding specific G6PD diagnostic tests. The majority of data available investigating the contextual factors of interest relates to quantitative G6PD diagnostic tests. While a formal qualitative synthesis of this data as part of a systematic review is possible, the data may be too heterogenous for this to be appropriate. These results can now be used to inform future direction of WHO Guideline Development Groups for G6PD near patient tests to support radical cure of P. vivax malaria.

A 3-year-old Tanzanian Female with Glucose-6-Phosphate Dehydrogenase A- and a Novel Heterozygous PIEZO1 Mutation (2744A>G, N915S) Presenting with Severe Hemolytic Anemia.

A 3-year-old Tanzanian female presented with severe hemolytic anemia of unknown etiology, necessitating multiple red blood cell transfusions. The patient was found to have glucose-6-phosphate dehydrogenase (G6PD) deficiency A- and a heterozygous Piezo-type mechanosensitive ion channel component 1 (PIEZO1) mutation (2744A>G, N915S). This case identifies a novel PIEZO1 mutation implicated in erythrocyte channelopathies occurring in conjunction with an X-linked enzymopathy in a female patient. This underscores the importance of keeping X-linked disorders in the differential diagnosis of hemolytic anemia in females, as well as presents the possibility for novel coexisting mutations to augment the phenotype.

RésuméUne Tanzanienne de 3 ans a présenté une anémie hémolytique sévère d'étiologie inconnue, nécessitant de multiples transfusions de globules rouges. Le patient présentait un déficit en glucose-6-phosphate déshydrogénase (G6PD) A- et un mécanosensible hétérozygote de type piézo.mutation du composant 1 du canal ionique (PIEZO1) (2744A>G, N915S). Ce cas identifie une nouvelle mutation PIEZO1 impliquée dans les érythrocytes canalopathies survenant en conjonction avec une enzymopathie liée à l'X chez une patiente. Cela souligne l'importance de garder troubles liés à l'X dans le diagnostic différentiel de l'anémie hémolytique chez les femmes, et présente la possibilité de nouvelles mutations coexistantes pour augmenter le phénotype.

Serum microRNAs as new biomarkers for detecting subclinical hemolysis in the nonacute phase of G6PD deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common enzymopathies worldwide. Patients with G6PD deficiency are usually asymptomatic throughout their life but can develop acute hemolysis after exposure to free radicals or certain medications. Several studies have shown that serum miRNAs can be used as prognostic biomarkers in various types of hemolytic anemias. However, the impact of G6PD deficiency on circulating miRNA profiles is largely unknown. The present study aimed to assess the use of serum miRNAs as biomarkers for detecting hemolysis in the nonacute phase of G6PD deficiency. Patients with severe or moderate G6PD Viangchan (871G > A) deficiency and normal G6PD patients were enrolled in the present study. The biochemical hemolysis indices were normal in the three groups, while the levels of serum miR-451a, miR-16, and miR-155 were significantly increased in patients with severe G6PD deficiency. In addition, 3D analysis of a set of three miRNAs (miR-451a, miR-16, and miR-155) was able to differentiate G6PD-deficient individuals from healthy individuals, suggesting that these three miRNAs may serve as potential biomarkers for patients in the nonhemolytic phase of G6PD deficiency. In conclusion, miRNAs can be utilized as additional biomarkers to detect hemolysis in the nonacute phase of G6PD deficiency.

Implementation of Universal Screening for G6PD Deficiency in Newborns.

We describe the implementation of universal glucose-6-phosphate dehydrogenase (G6PD) screening during the first year of New York State mandated testing, as well as operational challenges and clinical knowledge gained. All infants born at or transferred to our center between June 21, 2022 and June 30, 2023, underwent testing for G6PD enzyme deficiency and were included in the study cohort. Infant blood samples were collected and sent to a reference laboratory for quantitative assay. After initiation of universal screening, a quality improvement initiative was launched to: monitor and improve the suitability of blood sample collection to ensure timely return of results;improve the reliability and validity of the reference laboratory enzyme assay; andestablish accurate reference ranges for G6PD deficiency in newborns.A total of 5601 newborns were included. Within the first year of implementation, the percentage of samples yielding any test result increased from 76% to 85%, and most patients had a G6PD result available within 1 day of discharge. We established a more accurate threshold for G6PD deficiency in newborns of <4.9 U/g Hb and G6PD intermediate of <10.0 U/g Hb. Using the updated reference ranges, 224 patients in our cohort were identified as G6PD deficient or intermediate (4.0%). Through a quality-sensitive process, we identified the importance of a standardized approach, improved sample collection processes, decreased sample turnaround time, and established more accurate reference ranges. We hope our experiences will help others seeking to improve processes and implement similar programs at other institutions.

An Unexpected Finding of Klinefelter Syndrome during Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) Genetic Analysis.

BACKGROUND: Klinefelter syndrome is a common sex chromosome abnormality in males, characterized by an extra X chromosome compared to normal males. Glucose-6-phosphate dehydrogenase deficiency (G6PD) is an X-linked incomplete dominant defect disorder. In this study, we reported the unexpected detection of Klinefelter syndrome in a patient with G6PD. METHODS: G6PD enzyme activity was measured by immunoenzyme assay, and genetic analysis was performed using a fluorescent PCR melting curve method (PCR-melting curve). Sex chromosome number abnormalities were detected by multiplex ligation-dependent probe amplification (MLPA). The patient also underwent peripheral blood chromosome karyotype analysis. RESULTS: The patient's G6PD and 6PGD enzyme activities were 21.34 U/L and 22.85 U/L, respectively, and their ratio was below the reference range (0.93). The PCR-melting curve displayed a c.1388 heterozygous mutation in this boy, and the Sanger sequencing provided the same results. MLPA results suggested the presence of approxi-mately two copies of the X-chromosome in the boy. Finally, chromosome karyotype analysis confirmed that the boy had Klinefelter syndrome with a karyotype of 47, XXY. CONCLUSIONS: Klinefelter syndrome was accidentally detected during G6PD genetic analysis in a male. X-chromosomes can interfere with the results of G6PD genetic analysis and should be noted.

Perspectives of healthcare professionals on training for quantitative G6PD testing during implementation of tafenoquine in Brazil (QualiTRuST Study).

Effective radical cure of Plasmodium vivax malaria is essential for malaria elimination in Brazil. P. vivax radical cure requires administration of a schizonticide, such as chloroquine, plus an 8-aminoquinoline. However, 8-aminoquinolines cause hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, requiring prior screening to exclude those at risk. Brazil is pioneering the implementation of tafenoquine, a single-dose 8-aminoquinoline indicated for P. vivax patients with >70% of normal G6PD activity. Tafenoquine implementation in Manaus and Porto Velho, two municipalities located in the western Brazilian Amazon, included comprehensive training of healthcare professionals (HCPs) on point-of-care quantitative G6PD testing and a new treatment algorithm for P. vivax radical cure incorporating tafenoquine. Training was initially provided to higher-level facilities (phase one) and later adapted for primary care units (phase two). This study analyzed HCP experiences during training and implementation and identified barriers and facilitators. In-depth interviews and focus discussion groups were conducted 30 days after each training for a purposive random sample of 115 HCPs. Thematic analysis was employed using MAXQDA software, analyzing data through inductive and deductive coding. Analysis showed that following the initial training for higher-level facilities, some HCPs did not feel confident performing quantitative G6PD testing and prescribing the tafenoquine regimen. Modifications to the training in phase two resulted in an improvement in understanding the implementation process of the G6PD test and tafenoquine, as well as in the knowledge acquired by HCPs. Additionally, knowledge gaps were addressed through in situ training, peer communication via a messaging app, and educational materials. Training supported effective deployment of the new tools in Manaus and Porto Velho and increased awareness of the need for pharmacovigilance. A training approach for nationwide implementation of these tools was devised. Implementing quantitative G6PD testing and tafenoquine represents a significant shift in P. vivax malaria case management. Consistent engagement with HCPs is needed to overcome challenges in fully integrating these tools within the Brazilian health system.

Exploring Appropriate Reference Intervals and Clinical Decision Limits for Glucose-6-Phosphate Dehydrogenase Activity in Individuals From Guangzhou, China.

Background: Quantitative detection of glucose-6-phosphate dehydrogenase (G6PD) is commonly done to screen for G6PD deficiency. However, current reference intervals (RIs) of G6PD are unsuitable for evaluating G6PD-activity levels with local populations or associating G6PD variants with hemolysis risk to aid clinical decision-making. We explored appropriate RIs and clinical decision limits (CDLs) for G6PD activity in individuals from Guangzhou, China. Methods: We enrolled 5,852 unrelated individuals between 2020 and 2022 and screened their samples in quantitative assays for G6PD activity. We conducted further investigations, including G6PD genotyping, thalassemia genotyping, follow-up analysis, and statistical analysis, for different groups. Results: In Guangzhou, the RIs for the G6PD activities were 11.20-20.04 U/g Hb in male and 12.29-23.16 U/g Hb in female. The adjusted male median and normal male median (NMM) values were 15.47 U/g Hb and 15.51 U/g Hb, respectively. A threshold of 45% of the NMM could be used as a CDL to estimate the probability of G6PD variants. Our results revealed high hemolysis-risk CDLs (male: <10% of the NMM, female: <30% of the NMM), medium hemolysis-risk CDLs (male: 10%-45% of the NMM, female: 30%-79% of the NMM), and low hemolysis-risk CDLs (male: ≥ 45% of the NMM, female: ≥ 79% of the NMM). Conclusions: Collectively, our findings contribute to a more accurate evaluation of G6PD-activity levels within the local population and provide valuable insights for clinical decision-making. Specifically, identifying threshold values for G6PD variants and hemolysis risk enables improved prediction and management of G6PD deficiency, ultimately enhancing patient care and treatment outcomes.

The PreQuine Platform: A novel diagnostic tool for measuring glucose-6-phosphate dehydrogenase (G6PD) activity and hemoglobin concentration.

Quantitative diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is essential for the safe administration of 8-aminoquinoline based radical cure for the treatment of Plasmodium vivax infections. Here, we present the PreQuine Platform (IVDS, USA), a quantitative biosensor that uses a dual-analyte assay for the simultaneous measurement of Hemoglobin (Hgb) levels and G6PD enzyme activity within the same sample. The platform relies on a downloadable mobile application. The device requires 10µl of whole blood and works with a reflectance-based meter. Comparing the G6PD measurement normalized by Hgb of 12 samples from the PreQuine Platform with reference measurements methods (spectrophotometry, Pointe Scientific, USA and hemoglobin meter, HemoCue, Sweden) showed a positive and significant agreement with a slope of 1.0091 and an intercept of -0.0379 under laboratory conditions. Next steps will be to conduct field trials in Bangladesh, Cambodia, and the USA to assess diagnostic performance, user friendliness and acceptance.

Field evaluation of a novel semi-quantitative point-of-care diagnostic for G6PD deficiency in Indonesia.

BACKGROUND: The WHO recommends routine testing of G6PD activity to guide radical cure in patients with Plasmodium vivax malaria. Females may have intermediate G6PD enzyme activity and to date, only complex diagnostics are able to reliably identify them. The semi-quantitative G6PD diagnostic "One Step G6PD Test" (Humasis, RoK; "RDT") is a lateral flow assay that can distinguish deficient, intermediate, and normal G6PD status and offers a simpler diagnostic alternative. METHODS: G6PD status of participants enrolled in Malinau and Nunukan Regencies and the capital Jakarta was assessed with the RDT, and G6PD activity was measured in duplicate by reference spectrophotometry. The adjusted male median (AMM) of the spectrophotometry measurements was defined as 100% activity; 70% and 30% of the AMM were defined as thresholds for intermediate and deficient G6PD status, respectively. Results were compared to those derived from spectrophotometry at the clinically relevant G6PD activity thresholds of 30% and 70%. RESULTS: Of the 161 participants enrolled, 10 (6.2%) were G6PD deficient and 12 (7.5%) had intermediate G6PD activity by spectrophotometry. At the 30% threshold, the sensitivity of the RDT was 10.0% (95%CI: 0.3-44.5%) with a specificity of 99.3% (95%CI: 96.4-100.0%); the positive predictive value was 50.0% (95%CI: 1.3-98.7%) and the negative predictive value 94.3% (95%CI: 89.5-97.4%). The corresponding figures at the 70% threshold were 22.7% (95%CI: 7.8-45.4%), 100.0% (95%CI: 97.4-100.0%), 100.0% (95%CI: 47.8-100.0%) and 89.1% (95%CI: 83.1-93.5%), respectively. CONCLUSION: While there is a dire need for an easy-to-use, economical, semi-quantitative diagnostic for the point of care, the observed performance of the "One Step G6PD Test" in its current form was insufficient to guide antimalarial treatment.

Newborn screening in Colombia: The experience of a private program in Bogotá / Tamizaje neonatal en Colombia: la experiencia de un programa privado en Bogotá.

Introduction. The first neonatal screening program in Colombia ­ PREGEN ­ was set up in the medical private sector of Bogotá in 1988. We report the results from recent years that, given the scarcity of similar information in our country, may help estimate the frequency of the evaluated neonatal disorders and which ones should be included in the neonatal screening programs in our country. Objective. To describe the results of PREGEN´s newborn screening program between 2006 and 2019. Materials and methods. We analyzed databases and other informative documents preserved in PREGEN from the 2006-2019 period. Results. One in every 164 newborns screened in our program had an abnormal hemoglobin variant, and one in every 194 carried some hemoglobin S variant. Glucose-6- phosphate dehydrogenase deficiency and congenital hypothyroidism are next as the more common disorders. Conclusions. Abnormal hemoglobin causes the most frequent monogenic disorder in the world. Glucose-6-phosphate dehydrogenase deficiency is the most common enzymopathy affecting nearly 400 million individuals worldwide. Since both disorders are more common in people of African descent and confer some resistance to malaria, we believe that screening for both disorders may be more relevant in the areas with African ancestry in our country.

Introducción. En Colombia, el primer programa de tamizaje neonatal, PREGEN, inició labores en el sector privado de Bogotá en 1988. En este artículo se presentan los resultados obtenidos en los últimos años, que, dada la carencia de estos estudios en el país, pueden servir para evaluar la frecuencia de aparición de los trastornos congénitos evaluados y estimar cuáles de ellos deben ser objeto de tamizaje neonatal a nivel nacional. Objetivos. Reportar los resultados del programa de tamizaje PREGEN entre el 2006 y el 2019. Materiales y métodos. Para este análisis se examinaron las bases de datos y otros documentos informativos de PREGEN para el periodo 2006-2019. Resultados. Uno de cada 164 recién nacidos tamizados en el programa PREGEN en Bogotá presentó una variante anormal de la hemoglobina y uno de cada 194 es portador de hemoglobina S. Los siguientes dos trastornos más frecuentes encontrados fueron la deficiencia de la enzima glucosa-6-fosfato deshidrogenasa (frecuencia 1:2.231) y el hipotiroidismo congénito (frecuencia 1:3.915). Conclusiones. Las hemoglobinopatías mostraron ser uno de los desórdenes monogénicos más comunes, seguidos por la deficiencia de glucosa-6-fosfato deshidrogenasa y el hipotiroidismo congénito. Se calcula que cerca de 400 millones de personas en el mundo están afectadas por la deficiencia de glucosa-6-fosfato deshidrogenasa, por lo cual es la enzimopatía más común en el mundo. Como ambos desórdenes son más frecuentes en poblaciones de origen africano y confieren algún grado de resistencia a la malaria, es de prever que su tamizaje debe ser de mayor importancia en las zonas con ancestros africanos en Colombia.

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Gia Lai Province, Vietnam.

Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) deficiency is one of the most common X-linked hereditary disorders worldwide. G6PD deficiency provides resistance against severe malaria, but paradoxically, G6PD deficiency is also a stumbling block in fighting against malaria. Primaquine (PQ), a drug for the radical cure of Plasmodium vivax, can cause lethal acute hemolytic anemia in malaria patients with inherited G6PD deficiency. In this study, we analyzed the phenotypic and genotypic G6PD deficiency status in 1721 individuals (963 males and 758 females) residing in three malaria-endemic areas within the Gia Lai province, Vietnam. The G6PD activity in individuals ranged from 3.04 to 47.82 U/g Hb, with the adjusted male median (AMM) of 7.89 U/g Hb. Based on the G6PD activity assay results, no phenotypic G6PD deficiency was detected. However, the multiplex polymerase chain reaction to detect G6PD variations in the gene level revealed that 26 individuals (7 males, 19 females) had Viangchan mutations (871 G > A). Sequencing analyses suggested that all the males were hemizygous Viangchan, whereas one was homozygous, and 18 were heterozygous Viangchan in females. These results suggested a relatively low prevalence of G6PD deficiency mutation rate (1.51%) in the minor ethnic populations residing in the Gia Lai province, Vietnam. However, considering these areas are high-risk malaria endemic, concern for proper and safe use of PQ as a radical cure of malaria is needed by combining a G6PD deficiency test before PQ prescription.

Glucose-6-phosphate dehydrogenase deficiency with coinherited Gaucher disease: A rare association.

ABSTRACT: Anemia coexisting with Gaucher disease (GD) is often associated with non-hemolytic processes. Few cases of GD with autoimmune hemolytic anemia have been reported. However, literature on GD with concomitant nonimmune hemolytic anemia is scarce. A 1-year 6-month-old male child presented in 2018 with complaints of palpable mass in left upper abdomen, fever, cough, and vomiting. On examination, he had pallor, hepatosplenomegaly of 2 cm and 8 cm below costal margin, respectively. A clinical diagnosis of hemolytic anemia was suspected. Complete blood count revealed Hb---6.7 g/dL, TLC---8.9 × 10 3 /µL, platelet count---180 × 10 3 /µL. Peripheral smear showed predominantly microcytic hypochromic anemia with moderate degree of anisocytosis, many nucleated red blood cells, few schistocytes, polychromatophils and corrected reticulocyte count 7.89%. S. Bilirubin was 1.1 mg/dL. Hb high-performance liquid chromatography (HPLC) of the child and his parents was within normal limit. Hematological work up revealed negative results for direct Coombs' test, osmotic fragility test, and sickling test. Test for Glucose-6-phosphate dehydrogenase deficiency was positive (39 units/trillion RBC, normal 146--376). He was transfused intermittently and given steroids to manage his anemia. He was on regular follow up during which his blood counts revealed persistent anemia and thrombocytopenia. In view of this, bone marrow was performed to exclude myelofibrosis. Aspirate smears were cellular and showed normoblastic erythroid hyperplasia. Numerous large histiocytes with basophilic fibrillary cytoplasm exhibiting "crumpled tissue paper" appearance were seen. Similar findings were seen on bone marrow trephine biopsy. Genetic testing revealed pathogenic variations in the GBA gene. Beta glucosidase enzyme levels were low while chitotriosidase was raised (1109.19 nmol/hr/mL). A final diagnosis of G6PD with GD was made. The present study shows rare association of GD with Glucose-6-phosphate dehydrogenase deficiency.

Genetic analysis and molecular basis of G6PD deficiency among malaria patients in Thailand: implications for safe use of 8-aminoquinolines.

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 (< 30% activity) was 6.13% (25/408) and intermediate deficiency (30-70% activity) was found in 15.20% (62/408) of participants. Several G6PD genotypes with newly discovered double missense variants were identified by HRM assays, including G6PD Gaohe + Viangchan, G6PD Valladolid + Viangchan and G6PD Canton + Viangchan. A significantly high frequency of synonymous (c.1311C>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.

Field assessment of the operating procedures of a semi-quantitative G6PD Biosensor to improve repeatability of routine testing.

In remote communities, diagnosis of G6PD deficiency is challenging. We assessed the impact of modified test procedures and delayed testing for the point-of-care diagnostic STANDARD G6PD (SDBiosensor, RoK), and evaluated recommended cut-offs. We tested capillary blood from fingerpricks (Standard Method) and a microtainer (BD, USA; Method 1), venous blood from a vacutainer (BD, USA; Method 2), varied sample application methods (Methods 3), and used micropipettes rather than the test's single-use pipette (Method 4). Repeatability was assessed by comparing median differences between paired measurements. All methods were tested 20 times under laboratory conditions on three volunteers. The Standard Method and the method with best repeatability were tested in Indonesia and Nepal. In Indonesia 60 participants were tested in duplicate by both methods, in Nepal 120 participants were tested in duplicate by either method. The adjusted male median (AMM) of the Biosensor Standard Method readings was defined as 100% activity. In Indonesia, the difference between paired readings of the Standard and modified methods was compared to assess the impact of delayed testing. In the pilot study repeatability didn't differ significantly (p = 0.381); Method 3 showed lowest variability. One Nepalese participant had <30% activity, one Indonesian and 10 Nepalese participants had intermediate activity (≥30% to <70% activity). Repeatability didn't differ significantly in Indonesia (Standard: 0.2U/gHb [IQR: 0.1-0.4]; Method 3: 0.3U/gHb [IQR: 0.1-0.5]; p = 0.425) or Nepal (Standard: 0.4U/gHb [IQR: 0.2-0.6]; Method 3: 0.3U/gHb [IQR: 0.1-0.6]; p = 0.330). Median G6PD measurements by Method 3 were 0.4U/gHb (IQR: -0.2 to 0.7, p = 0.005) higher after a 5-hour delay compared to the Standard Method. The definition of 100% activity by the Standard Method matched the manufacturer-recommended cut-off for 70% activity. We couldn't improve repeatability. Delays of up to 5 hours didn't result in a clinically relevant difference in measured G6PD activity. The manufacturer's recommended cut-off for intermediate deficiency is conservative.

Screening results and mutation frequency analysis of G6PD deficiency in 1,291,274 newborns in Huizhou, China: a twenty-year experience.

OBJECTIVES: This study aimed to investigate the incidence rate and spectrum of gene mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Huizhou city of southern China to provide a scientific basis for disease prevention and control in the area. METHODS: From March 2003 to December 2022, newborn screening for G6PD enzyme activity was carried out in Huizhou city using the fluorescence quantitative method. Infants who tested positive during the initial screening were diagnosed using the nitroblue tetrazolium ratio method, while a subset of infants received further gene mutation analysis using the multicolor probe melting curve analysis method. RESULTS: A total of 1,291,274 newborns were screened and the screening rate has increased from 20.39% to almost 100%. In the 20-year period, 57,217 (4.43%) infants testing positive during the initial screening. Out of these infants, 49,779 (87%) were recalled for confirmatory testing. G6PD deficiency was confirmed in 39,261 of the recalled infants, indicating a positive predictive value of 78.87%. The estimated incidence rate of G6PD deficiency in the region was 3.49%, which was significantly higher than the average incidence rate of 2.1% in southern China. On the other hand, seven pathogenic G6PD variants were identified in the analysis of the 99 diagnosed infants with the most common being c.1388 G > A (48.5%), followed by c.95 A > G (19.2%), c.1376 G > T (15.2%), c.871 G > A (9.1%), c.1360 C > T (3.0%), c.392 G > T (3.0%), and c.487 G > A (1.0%). CONCLUSION: The incidence of G6PD deficiency in newborns in the Huizhou city was higher than the southern China average level, while the types and frequencies of gene mutations were found to vary slightly from other regions. Our findings suggested that free government screening and nearby diagnosis strategies could reduce the incidence of G6PD deficiency in the area.

Glucose-6-phosphate dehydrogenase deficiency and psychotic disorders: A systematic review.

OBJECTIVES: Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) is the most common enzymopathy globally. Early studies suggested an association with severe psychotic illness; however, changes to laboratory testing and diagnostic classification renders the association unclear. This study aims to explore the interaction between G6PD deficiency and psychotic symptoms, in particular to identify specific patterns of presentation or impact on outcomes. METHODS: Pubmed, Embase, and PsycInfo databases were searched from inception to May 2023. Descriptive statistics and narrative review of were used to synthesise data on demographics, mental and physical health diagnoses, investigations, treatment, and outcomes. RESULTS: No clear link was found in published data (eight case reports, case series of n = 29) with a high rate (63%) of haemolytic crisis at the time of psychiatric presentation suggested delirium as an alternative diagnosis. Four case control studies found no significant difference in the prevalence of G6PD deficiency. However, catatonic presentation was reported in 40% of the case series and a higher prevalence of G6PD deficiency in catatonic schizophrenia was noted in case control studies. CONCLUSIONS: Based on the information available there was no clear association between G6PD deficiency and psychotic illness or treatment resistance, although paucity of studies and risk of bias limit strong conclusions.

Prevalence and molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Senoi Malaysian Orang Asli population.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder characterized by reduced G6PD enzyme levels in the blood. This condition is common in populations exposed to malaria; an acute febrile disease caused by Plasmodium parasites. G6PD-deficient individuals may suffer from acute hemolysis following the prescription of Primaquine, an antimalarial treatment. The population at risk for such a condition includes the Senoi group of Orang Asli, a remote indigenous community in Malaysia. This study aimed to elucidate the G6PD molecular heterogeneity in this subethnic group which is important for malaria elimination. A total of 662 blood samples (369 males and 293 females) from the Senoi subethnic group were screened for G6PD deficiency using a quantitative G6PD assay, OSMMR2000-D kit with Hb normalization. After excluding the family members, the overall prevalence of G6PD deficiency in the studied population was 15.2% (95% CI: 11-19%; 56 of 369), with males (30 of 172; 17.4%) outnumbering females (26 of 197; 13.2%). The adjusted male median (AMM), defined as 100% G6PD activity, was 11.8 IU/gHb. A total of 36 participants (9.6%; 26 male and 10 female) were deficient (<30% of AMM) and 20 participants (5.4%; 4 male and 16 female) were G6PD-intermediate (30-70% of AMM). A total of 87 samples were genotyped, of which 18 showed no mutation. Seven mutations were found among 69 genotyped samples; IVS11 T93C (47.1%; n = 41), rs1050757 (3'UTR +357A>G)(39.1%; n = 34), G6PD Viangchan (c.871G>A)(25.3%; n = 22), G6PD Union (c.1360C>T)(21.8%; n = 19), c.1311C>T(20.7%; n = 18), G6PD Kaiping (c.1388G>A)(8.0%; n = 7), and G6PD Coimbra (c.592C>T)(2.3%; n = 2). Our analysis revealed 27 hemizygote males, 18 heterozygote females, 7 homozygote females, and 2 compound heterozygote females. This study confirms the high prevalence of G6PD deficiency among the Senoi Malaysian Orang Asli, with a significant degree of molecular heterogeneity. More emphasis should be placed on screening for G6PD status and proper and safe use of Primaquine in the elimination of malaria among this indigenous population.