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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. [ABSTRACT FROM AUTHOR]

Background and aims: Newborn screening (NBS) for glucose-6-phosphate dehydrogenase (G6PD) deficiency by biochemical tests is being used worldwide, however, the outcomes arising from combined genetic and biochemical tests have not been evaluated. This research aimed to evaluate the outcomes of application of combined genetic and biochemical NBS for G6PD deficiency and to investigate the molecular epidemiological characteristics, variant spectrum, and genotype-phenotype correlation of G6PD deficiency in China. Methods: A population-based cohort of 29,601 newborns were prospectively recruited from eight NBS centers in China between February 21 and December 30, 2021. Biochemical and genetic NBS was conducted simultaneously. Results: The overall prevalence of G6PD deficiency was 1.12% (1.86% for male, and 0.33% for female; 1.94% for South China and 0.08% for North China). Genetic NBS identified 10 male patients undetected by biochemical NBS. The overall positive predictive values (PPVs) of biochemical and genetic NBS were 79.95% and 47.57%, respectively. A total of 15 variants were identified, with the six most common variants being c.1388G > A, c.1376G > T, c.95A > G, c.871G > A, c.1024C > T and c.392G > T (94.2%). The activity of G6PD was correlated with the type and WHO classification of variants. Conclusion: This study highlighted that combined screening could enhance the efficiency of current NBS for diagnosing G6PD deficiency. The prevalence, variant spectrum and allele frequency of G6PD deficiency vary across different regions. Our data provide valuable references for clinical practice and optimization of future screening strategies for G6PD deficiency. [ABSTRACT FROM AUTHOR]

The article delves into the reconsideration of leukoreduction of whole blood for patients facing life-threatening hemorrhage, particularly in trauma centers and military blood programs. It examines the benefits and limitations of leukoreduction in reducing febrile reactions, CMV transmission, and HLA alloimmunization, as well as the operational challenges and benefits. The text also compares the use of leukoreduced (LR) and non-LR whole blood for transfusion purposes, highlighting cost implications, shelf life differences, and the need for further clinical trials to determine effects on patient outcomes. The article underscores the importance of carefully weighing the potential benefits and risks of using LR versus non-LR whole blood in clinical decision-making for patients with major bleeding. [Extracted from the article]

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders due to pathogenic variants in genes encoding enzymes and cofactors involved in adrenal steroidogenesis. Although 21‐hydroxylase, 11β‐hydroxylase, 3β‐hydroxysteroid dehydrogenase type 2, 17α‐hydroxylase/17,20‐lyase, P450 oxidoreductase, steroidogenic acute regulatory protein, cholesterol side‐chain cleavage enzyme deficiencies are considered within the definition of CAH, the term 'CAH' is often used to refer to '21‐hydroxylase deficiency (21OHD)' since 21OHD accounts for approximately 95% of CAH in most populations. The prevalence of the rare forms of CAH varies according to ethnicity and geographical location. In most cases, the biochemical fingerprint of impaired steroidogenesis points to the specific subtypes of CAH, and genetic testing is usually required to confirm the diagnosis. Despite there are significant variations in clinical characteristics and management, most data about the rare CAH forms are extrapolated from 21OHD. This review article aims to collate the currently available data about the diagnosis and the management of rare forms of CAH. [ABSTRACT FROM AUTHOR]

Background and Objectives: To investigate the prevalence, genotype and haematological characteristics of glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in the blood donor population of Wuxi area (Jiangsu Province, China) and to assess the impact of their red blood cell (RBC) units on clinical transfusion. Materials and Methods: We conducted genotyping and large‐scale screening for G6PD enzyme activity in the blood donors of Wuxi City. In addition, we assessed the haematological parameters of G6PD‐deficient and non‐deficient blood donors, and investigated the adverse transfusion reactions in patients transfused with G6PD‐deficient blood. Results: We investigated 17,113 blood donors, among whom 44 (0.26%) were tested positive for G6PD deficiency. We identified 40 G6PD gene variants, among which c.1388G>A, c.1376G>T, c.1024C>T and c.95A>G were common. In addition, we identified two novel G6PD gene variants, c.1312G>A and c.1316G>A. The G6PD‐deficient and non‐deficient blood samples showed a significant difference in the RBC, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), RBC distribution width, total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) values. However, the two samples showed no significant difference in the haemolysis rate at the end of the storage period. Finally, transfusion with G6PD‐deficient RBC units did not lead to any adverse transfusion reactions. Conclusion: The positive rate of G6PD deficiency in the blood donor population of Wuxi City is 0.26%, and the genetic variants identified in this population are consistent with the common genetic variants observed in the Chinese population. Blood centres can establish a database on G6PD‐deficient blood donors and mark their RBC units to avoid their use for special clinical patients. [ABSTRACT FROM AUTHOR]

Extreme levels of bilirubin in newborn is a major cause of lifelong neurodevelopmental impairment, which places a financial burden on healthcare resources and caregivers. To determine the incidence, aetiology and short-term outcomes of extreme hyperbilirubinaemia in term infants born in a resource-limited setting. This is a retrospective observational study looking at term neonates with a birth weight ≥2500 g, born in the Western health subdistrict of Cape Town, South Africa, between 1 January 2019 and 31 December 2020, who were exposed to a serum bilirubin level of ≥430 μmol/L in the first week of life and received care in the public health system. Extreme hyperbilirubinaemia occurred in 59 term infants. The incidence was 74 cases per 100 000 (<0.01%) live births equating to 1 case in every 1345 live births. The cause of hyperbilirubinaemia was identified in 51 of the cases (86%), the most common being ABO incompatibility (31/51, 61%), followed by glucose-6-phosphate dehydrogenase deficiency (11/51, 22%). Twelve infants (20 %) underwent an exchange transfusion. Six infants were encephalopathic. Forty-seven infants (80%) were readmitted after initial post-natal discharge, with a mean age of readmission of 113 h old (SD 31 h). The incidence of extreme hyperbilirubinaemia in the Western health subdistrict of Cape Town is higher than in high-income settings. Further work should focus on training of healthcare workers and education of caregivers, for the early detection of significant hyperbilirubinaemia to prevent neurological complications caused by bilirubin toxicity. [ABSTRACT FROM AUTHOR]

Plasmodium vivax is a major cause of malaria, which poses an increased health burden on approximately one third of the world's population due to climate change. Primaquine, the preferred treatment for P. vivax malaria, is contraindicated in individuals with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, a common genetic cause of hemolytic anemia, that affects ∼2.5% of the world's population and ∼8% of the population in areas of the world where P. vivax malaria is endemic. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) conducted a structure–function analysis of P. vivaxN‐myristoyltransferase (PvNMT) as part of efforts to develop alternative malaria drugs. PvNMT catalyzes the attachment of myristate to the N‐terminal glycine of many proteins, and this critical post‐translational modification is required for the survival of P. vivax. The first step is the formation of a PvNMT–myristoyl–CoA binary complex that can bind to peptides. Understanding how inhibitors prevent protein binding will facilitate the development of PvNMT as a viable drug target. NMTs are secreted in all life stages of malarial parasites, making them attractive targets, unlike current antimalarials that are only effective during the plasmodial erythrocytic stages. The 2.3 Å resolution crystal structure of the ternary complex of PvNMT with myristoyl‐CoA and a novel inhibitor is reported. One asymmetric unit contains two monomers. The structure reveals notable differences between the PvNMT and human enzymes and similarities to other plasmodial NMTs that can be exploited to develop new antimalarials. [ABSTRACT FROM AUTHOR]

Background/Aims: Glucose-6-phosphate dehydrogenase deficiency worsens the risk of anaemia and complicates gestation and birth if poorly managed. This study investigated the prevalence and factors associated with anaemia and this deficiency in pregnant women. Methods: This cross-sectional study was conducted among 369 pregnant women at the Cape Coast Metropolitan Hospital, Ghana. Multiple logistic regression was used to investigate the relationship between anaemia and various sociodemographic variables. Results: The prevalence of anaemia was 41.2% at 13 weeks' and 66.7% at 36 weeks' gestation. Overall, 29.8% of participants were glucose-6-phosphate dehydrogenase deficient. Age (P=0.024)and marital status (P=0.009) were significantly associated with anaemia at 13 weeks. Gravidity (P=0.014) and employment status (P=0.001) were significantly associated with anaemia at 36 weeks. Conclusions: There was a high prevalence of co-morbid anaemia and glucose-6-phosphate dehydrogenase deficiency at 13 and 36 weeks' gestation. Future studies should consider genetic and dietary factors that may contribute to gestational anaemia. Implications for practice: Clinicians and midwives should be aware of the factors that can affect anaemia and glucose-6-phosphate dehydrogenase deficiency, particularly in areas where deficiency is prevalent. Early detection could allow individualised treatment. [ABSTRACT FROM AUTHOR]

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Summary G6PD deficiency results from mutations in the X‐linked G6PD gene. More than 200 variants are associated with enzyme deficiency: each one of them may either cause predisposition to haemolytic anaemia triggered by exogenous agents (class B variants), or may cause a chronic haemolytic disorder (class A variants). Genotype–phenotype correlations are subtle. We report a rare G6PD variant, discovered in a baby presenting with severe jaundice and haemolytic anaemia since birth: the mutation of this class A variant was found to be p.(Arg454Pro). Two variants affecting the same codon were already known: G6PD Union, p.(Arg454Cys), and G6PD Andalus, p.(Arg454His). Both these class B variants and our class A variant exhibit severe G6PD deficiency. By molecular dynamics simulations, we performed a comparative analysis of the three mutants and of the wild‐type G6PD. We found that the tetrameric structure of the enzyme is not perturbed in any of the variants; instead, loss of the positively charged Arg residue causes marked variant‐specific rearrangement of hydrogen bonds, and it influences interactions with the substrates G6P and NADP. These findings explain severe deficiency of enzyme activity and may account for p.(Arg454Pro) expressing a more severe clinical phenotype. [ABSTRACT FROM AUTHOR]

Background: Radical cure of Plasmodium vivax infections is key to the control of vivax malaria. However, the standard doses of 8-aminoquinoline drugs used for radical cure can cause severe haemolysis in G6PD-deficient patients. The availability of near-patient G6PD tests could increase use of primaquine (PQ), however direct evidence of the impacts that G6PD testing has on downstream patient outcomes, such as haemolysis and recurrence is lacking. Methodology/Principle findings: A linked-evidence model was created to investigate changes in the number of severe haemolysis events and P. vivax recurrences within 6 months of treatment when qualitative G6PD testing was used to guide PQ treatment (0.25mg/kg/day for 14 days and 0.5mg/kg/day for 7 days), compared to prescribing 14-day PQ with no G6PD testing. In the model patients identified as G6PD-deficient received 8-week PQ (0.75mg/kg/week). The model was used to simulate scenarios with 1%, 5% and 10% prevalence of G6PD-deficiency (G6PDd) in theoretical populations of 10,000 male and female P. vivax patients and initially assumed 100% adherence to the prescribed PQ regiment. Results illustrate that G6PD testing to guide the 14-day PQ regiment reduced severe haemolysis by 21–80% and increased recurrences by 3–6%, compared to applying the 14-day PQ regiment without G6PD testing. Results for the 7-day PQ regiment informed by G6PD testing were mixed, dependent on G6PDd prevalence and sex. When adherence to the PQ regiments was less than perfect the model predicted reductions in the number of recurrences at all prevalence levels, provided adherence to 7-day PQ was 5–10% higher than adherence to the 14-day regiment. Conclusions/Significance: Introduction of G6PD testing to guide PQ treatment reduces severe haemolysis events for the 14-day regiment, and the 7-day regiment in higher G6PDd prevalence settings, compared to use of 14-day PQ without G6PD testing when all patients adhere to the prescribed PQ treatment. At a population level, there were increases in recurrences, but this could be resolved when the 7-day regiment was used and had superior adherence compared to the 14-day regiment. Author summary: To eliminate vivax malaria treatment is required that cures the blood infection and also kills any dormant parasites in the liver (called hypnozoites). Unfortunately, drugs currently available to treat hypnozoites such as primaquine can cause severe haemolysis when given to patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common human enzyme polymorphism. The author created a mathematical model that compares the number of severe haemolysis events and vivax recurrences within 6 months of treatment in a theoretical population when qualitative G6PD tests are used to guide primaquine treatment versus the use of primaquine without consideration of the G6PD status of the patient. The results demonstrate that adding G6PD tests into the clinical pathway can reduce the number of severe haemolysis events, but may increase the number of recurrences, with specific results determined by the prevalence of G6PD deficiency, the dosing regiment and adherence to the prescribed primaquine treatment. [ABSTRACT FROM AUTHOR]

Background: Primaquine (PQ) has activity against mature P. falciparum gametocytes and proven transmission blocking efficacy (TBE) between humans and mosquitoes. WHO formerly recommended a single transmission blocking dose of 0.75 mg/kg but this was little used. Then in 2012, faced with the emergence of artemisinin-resistant P. falciparum (ARPf) in SE Asia, the WHO recommended a lower dose of 0.25 mg/kg to be added to artemisinin-based combination therapy in falciparum-infected patients in low transmission areas. This dose was considered safe in glucose-6-phosphate dehydrogenase deficiency (G6PDd) and not requiring G6PD testing. Subsequent single low-dose primaquine (SLDPQ) studies have demonstrated safety in different G6PD variants. Dosing remains challenging in children under the age of 5 because of the paucity of PQ pharmacokinetic (PK) data. We plan to assess the anti-infectivity efficacy of SLDPQ using an allometrically scaled, weight-based regimen, with a target dose of 0.25 mg/kg, in children with acute uncomplicated falciparum malaria. Methods: This study is an open label, randomised 1:1, phase IIb study to assess TBE, tolerability, pharmacokinetics and acceptability of artesunate pyronaridine (ASPYR) administered alone or combined with SLDPQ in 56 Burkinabe children aged ≥ 6 months– < 5 years, with uncomplicated P. falciparum and a haemoglobin (Hb) concentration of ≥ 5 g/dL. We will assess TBE, using direct membrane feeding assays (DMFA), and further investigate PQ pharmacokinetics, adverse events, Hb dynamics, G6PD, sickle cells, thalassaemia and cytochrome 2D6 (CYP2D6) status, acceptability of flavoured PQ [CAST—ClinSearch Acceptability Score Test®], and the population's knowledge, attitude and practices on malaria. Expected results and discussion: We expect children to accept tablets, confirm the TBE and gametocytocidal effects of SLDPQ and then construct a PK infectivity model (including age, sex, baseline Hb, G6PD and CYP2D6 status) to define the dose response TBE relationship that may lead to fine tuning our SLDPQ regimen. Our study will complement others that have examined factors associated with Hb dynamics and PQ PK. It will provide much needed, high-quality evidence of SLDPQ in sick African children and provide reassurance that SLDPQ should be used as a strategy against emerging ARPf in Africa. Trial registration: ISRCTN16297951. Registered on September 26, 2021 [ABSTRACT FROM AUTHOR]

Following the advent of direct-acting antivirals (DAAs), the treatment of hepatitis C virus (HCV) infection is now rarely challenging. However, data are still limited concerning DAA use in patients affected by glucose-6-phosphate dehydrogenase deficiency (G6PDd). Based on these considerations, the goal of this study was to evaluate the effectiveness and safety of DAAs in this subpopulation. A retrospective multicenter observational study (2015–2023) was conducted on all 2754 consecutive HCV-positive patients treated with first- and second-generation all-oral DAAs, and with a G6PDd diagnosis confirmed by quantitative testing (n = 38). At the treating clinician's discretion, an enhanced clinical and laboratory follow-up was performed, generally on a monthly basis both during treatment and up to six months after the end of it. Concerning hematochemical parameters, no significant differences were found between any considered time point. In all cases, no treatment-related adverse events were reported, and virologic response rates were as expected without G6PDd. In conclusion, in a large experience which, to the best of our knowledge, is unprecedented in the literature, the treatment of HCV hepatitis with nearly all available DAAs in patients with G6PDd as a comorbidity—a common occurrence in countries such as Italy—proved to be highly effective and safe. [ABSTRACT FROM AUTHOR]

Background: In humans with pheochromocytomas (PCCs), targeted metabolomics is used to determine the catecholamine phenotype or to uncover underlying pathogenic variants in tricarboxylic acid (TCA) cycle genes such as succinate dehydrogenase subunits (SDHx). Hypothesis/Objectives: To analyze catecholamine contents and TCA cycle metabolites of PCCs and normal adrenals (NAs). Animals: Ten healthy dogs, 21 dogs with PCC. Methods: Prospective observational study. Dogs diagnosed with PCC based on histopathological and immunohistochemical confirmation were included. Tissue catecholamine contents and TCA metabolites in PCCs and NAs were measured by liquid chromatography with mass spectrometry or electrochemical detection. Results: Compared to NAs, PCCs had significantly higher tissue proportion of norepinephrine (88% [median: range, 38%‐98%] vs 14% [11%‐26%]; P <.001), and significantly lower tissue proportion of epinephrine (12% [1%‐62%] vs 86% [74%‐89%]; P <.001). Pheochromocytomas exhibited significantly lower fumarate (0.4‐fold; P <.001), and malate (0.5‐fold; P =.008) contents than NAs. Citrate was significantly higher in PCCs than in NAs (1.6‐fold; P =.015). One dog in the PCC group had an aberrant succinate : fumarate ratio that was 25‐fold higher than in the other PCCs, suggesting an SDHx mutation. Conclusions and Clinical Importance: This study reveals a distinct catecholamine content and TCA cycle metabolite profile in PCCs. Metabolite profiling might be used to uncover underlying pathogenic variants in TCA cycle genes in dogs. [ABSTRACT FROM AUTHOR]

Since the FDA's approval of rasburicase use for treatment of tumor lysis syndrome (TLS), multiple cases of rasburicase-induced methemoglobinemia and hemolytic anemia have been reported among patients with G6PD deficiency. This study aims to provide a systematic review of cases reporting such adverse reactions to rasburicase. A literature review of published cases in PubMed, Embase, Cochrane, and Web of Science was conducted. Descriptive studies reporting cases of rasburicase-induced methemoglobinemia and/or hemolytic anemia in English were analyzed and summarized in this study. Forty-three cases, including a case from our institution, were included in this study. Most cases (60.5%) received rasburicase for TLS treatment. Almost all patients (93.8%) were tested for G6PD after rasburicase administration. The median time to symptom onset was 24 h. The median methemoglobin level was 10%, peaking after a median of 24 h. The median hemoglobin nadir was 6.1 g/dL, and most patients (n = 32) required blood transfusion. Out of 39 cases with reported outcomes, 35 patients (89.7%) recovered, while four patients (three females and one male) died. The median time to recovery was 4.5 days while the median time to death was 8 days. Screening for G6PD deficiency among high-risk patients is important but not practical in acutely severe settings. When prior screening for G6PD deficiency is not feasible, close monitoring for methemoglobinemia and hemolytic anemia is recommended. Exchange transfusion is increasingly reported as a potentially successful therapeutic modality. Ascorbic acid may provide limited benefits. Methylene blue should be avoided as it may exacerbate hemolysis among these patients. [ABSTRACT FROM AUTHOR]

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and variants of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene are the most common genetic causes of neonatal unconjugated hyperbilirubinemia (NUH). In this review, we searched PubMed for articles on the genetic causes of NUH published before December 31, 2022, and analyzed the data. On the basis of the results, we reached eight conclusions: (1) 37 mutations of the G6PD gene are associated with NUH; (2) the clinical manifestation of G6PD deficiency depends not only on ethnicity but also on the molecular mechanisms underlying the deficiency (and thus its severity); (3) of mutations in the UGT1A1 gene, homozygous c.−53A(TA) 6 TAA > A(TA) 7 TAA is the main cause of NUH in Caucasians and Africans, whereas homozygous c.211G > A is the main genetic cause of NUH in East Asians; (4) in Indonesian neonates, homozygous c.−3279T > G is the most common cause of NUH development, and neither c.−53 A(TA) 6 TAA > A(TA) 7 TAA nor c.211G > A causes it; (5) in breast-fed East Asian neonates, the TA7 repeat variant of the UGT1A1 gene protects against the development of NUH; (6) G6PD deficiency combined with homozygous c.211G > A variation of the UGT1A1 gene increases the risk of severe NUH; (7) in Pakistani and Caucasian patients with Crigler–Najjar syndrome type 2 (CN-2), point mutations of the UGT1A1 gene are widely distributed and frequently occur with variation at nucleotide −53, whereas in Asian patients with CN-2, compound homozygous variations in the coding region are frequently observed; and (8) records of G6PD deficiency and UGT1A1 variation status for a neonate offer useful pharmacogenomic information that can aid long-term care. These results indicate that timely diagnosis of NUH through molecular tests is crucial and that early initiation of treatment for the neonates and educational programs for their parents improves outcomes. [ABSTRACT FROM AUTHOR]

Succinate dehydrogenase (also known as complex II) plays a dual role in respiration by catalyzing the oxidation of succinate to fumarate in the tricarboxylic acid (TCA) cycle and transferring electrons from succinate to ubiquinone in the mitochondrial electron transport chain (ETC). Owing to the privileged position of SDH/CII, its dysfunction leads to TCA cycle arrest and altered respiration. This review aims to elucidate the widely documented profound metabolic effects of SDH/CII deficiency, along with the newly unveiled survival mechanisms in SDH/CII-deficient cells. Such an understanding reveals exploitable vulnerabilities for strategic targeting, which is crucial for the development of novel and more precise therapies for primary mitochondrial diseases, as well as for familial and sporadic cancers associated with SDH/CII mutations. [ABSTRACT FROM AUTHOR]

Purpose: Primaquine (PQ) is recommended for radical cure of Plasmodium vivax (Pv) malaria, but its utilization is still limited due to high risk of severe haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD-d). The aim of the present study is to assess the different genotypic variants leading to G6PD-d in Delhi and Goa regions of India. Methods: A total of 46 samples (34 retrospective Pv-mono-infected samples and 12 Pv-uninfected samples) were included in the study. Various genetic variants leading to G6PD-d were analysed by PCR amplification and DNA sequencing of different targeted exons of G6PD gene. Results: Molecular analysis showed presence of four mutations in study population viz. 1311 C > T, 34.1% & IVSXI 93T > C, 45.5% and two novel mutations 1388G > T, 2.3% and 1398 C > T, 2.3% (silent mutation). The bioinformatics and computational analysis demonstrate that the slight conformational changes caused by R643L mutation in protein are deleterious in nature. Conclusion: The observed mutations do not clarify the role or association between G6PD-d and Pv-infected cases. Further investigation is required in order to fully comprehend and analyse the precise role of these mutations with context to malaria infections. [ABSTRACT FROM AUTHOR]

Background and Objectives: To evaluate the clinical findings of glucose 6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) deficiency in prolonged jaundice and to determine whether the systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) can be used in the diagnosis of neonatal prolonged jaundice. Materials and Methods: Among full-term neonates with hyperbilirubinemia who were admitted to Medicine Hospital between January 2019 and January 2024 with the complaint of jaundice, 167 infants with a serum bilirubin level above 10 mg/dL, whose jaundice persisted after the 10th day, were included in this study. Results: G6PD activity was negatively correlated with NLR, SII, age, and hematocrit (Hct). There was a weak negative correlation between G6PD and NLR and a moderate negative correlation between G6PD activity and SII when adjusted for age and Hct. PK activity showed no significant correlation with G6PD, NLR, PLR, SII, age, and Hct. A linear relationship was observed between G6PD activity and SII and NLR. Conclusions: NLR and SII can be easily calculated in the evaluation of prolonged jaundice in G6PD deficiency has a considerable advantage. NLR and SII levels may contribute by preventing further tests for prolonged jaundice and regulating its treatment. It may be useful to form an opinion in emergencies and in early diagnostic period. [ABSTRACT FROM AUTHOR]

Background: Port Haercourt, capital of Rivers state of Nigeria, is the genere of an oil exploration industry, babies born in the environment could stand the risk exposure deterogenic agents.Infants who are Glucose-6-phosphate Dehydrogenase(GAPD) defiencient may develop jaundice when exposed to these noxious substances. The aim of this study was to determine the severity of Jaundice among GSPD deficient neonates at the University of Port-Harcourt Teaching Hospital, Port-Harcourt (UPTIT. Methods: A prospective study of 400 jaundiced neonates admitted into the Special Care Baby Unit (SCBU) of the UTTH from June 1 to December 31, 2006, was carried out. Physical examination of all the babies admitted, with special reference to jaundice, was done. A structured questionnaire was used to collect data on mother and neonate; such data included sociodemogrphics, exposure no icerogenic substances, history of peripurture pyrexia, prolonged rapture of foetal membrane, agent poser of jaundice, history of seizure, mode of treatment of jaundice and outcome. Two mils of venous blood withdrawn from each neonate was put in an EDTA Bottle and immediately sent to the laboratory for quantitative GSPD enzyme assay based on the method of Kumbery. Servia bilicubin level was estimated using the Van Berghdiaza reaction. Data were arranged in frequency tables and discrete variables were compared using Chi-square statistic, while continuous variables were corrpared using the student t test, in all instances, a p value of less than CCS was regarded as statisisticaly significant. Results: Out of the 400 jaundiced neonates, 215 (52.5 percent) were G6PD deficient, while 190 (7.5 percent) had normal G6PD activity. There were 145 (69. 0 percent) G6PD deficient males and 55 (31.0 percent) females. One hundred and Thirty-five (64.3 percent) of the G6PD deficient neonates were severely jaundiced (10% males and 29 feriales). A greater proportion of those with severe jaundice were 120 (X = 14.45; dE; - 0.0013). Eighty four (43.0 percent) of the G6PD defiicient neonates were exposed to icterogenic substances. Sixty eight (81.0 percent) of those so exposed were severely jaundiced, while the jaundice wasn ot severe in 19 (19.0 percent). That association between exposure to icterogenic substances and severity of jaundice was statistically significant (X- 15.75: - 1;p-0.000727). Clinical features of keruuser us were found in seven (1.2 percent) of the deficient neonates while 15 (17.1 percent) died. Conclusion: G6PD deficiency is commonly associated with severe neonatal jaundice, the severity of which is infuenced by gender and exposure to clerogenic substances. It is recommended that any neonates presenting with jaundice should be screen for G6PD states not only to define the actiology at hypetalubinscmia but also to prevent future bacurolytic episexles. Background: Port Haercourt, capital of Rivers state of Nigeria, is the genere of an oil exploration industry, babies born in the environment could stand the risk exposure deterogenic agents.Infants who are Glucose-6-phosphate Dehydrogenase(GAPD) defiencient may develop jaundice when exposed to these noxious substances. The aim of this study was to determine the severity of Jaundice among GSPD deficient neonates at the University of Port-Harcourt Teaching Hospital, Port-Harcourt (UPTIT. Methods: A prospective study of 400 jaundiced neonates admitted into the Special Care Baby Unit (SCBU) of the UTTH from June 1 to December 31, 2006, was carried out. Physical examination of all the babies admitted, with special reference to jaundice, was done. A structured questionnaire was used to collect data on mother and neonate; such data included sociodemogrphics, exposure no icerogenic substances, history of peripurture pyrexia, prolonged rapture of foetal membrane, agent poser of jaundice, history of seizure, mode of treatment of jaundice and outcome. Two mils of venous blood withdrawn from each neonate was put in an EDTA Bottle and immediately sent to the laboratory for quantitative GSPD enzyme assay based on the method of Kumbery. Servia bilicubin level was estimated using the Van Berghdiaza reaction. Data were arranged in frequency tables and discrete variables were compared using Chi-square statistic, while continuous variables were corrpared using the student t test, in all instances, a p value of less than CCS was regarded as statisisticaly significant. Results: Out of the 400 jaundiced neonates, 215 (52.5 percent) were G6PD deficient, while 190 (7.5 percent) had normal G6PD activity. There were 145 (69. 0 percent) G6PD deficient males and 55 (31.0 percent) females. One hundred and Thirty-five (64.3 percent) of the G6PD deficient neonates were severely jaundiced (10% males and 29 feriales). A greater proportion of those with severe jaundice were 120 (X = 14.45; dE; - 0.0013). Eighty four (43.0 percent) of the G6PD defiicient neonates were exposed to icterogenic substances. Sixty eight (81.0 percent) of those so exposed were severely jaundiced, while the jaundice wasn ot severe in 19 (19.0 percent). That association between exposure to icterogenic substances and severity of jaundice was statistically significant (X- 15.75: - 1;p-0.000727). Clinical features of keruuser us were found in seven (1.2 percent) of the deficient neonates while 15 (17.1 percent) died. Conclusion: G6PD deficiency is commonly associated with severe neonatal jaundice, the severity of which is infuenced by gender and exposure to clerogenic substances. It is recommended that any neonates presenting with jaundice should be screen for G6PD states not only to define the actiology at hypetalubinscmia but also to prevent future bacurolytic episexles.

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. [ABSTRACT FROM AUTHOR]

Background: Central nervous system tumors are the 10th most prevalent cause of mortality worldwide. The 2016 World Health Organization (WHO) classification of high grade gliomas (HGG) has identified Isocitrate dehydrogenase 1 (IDH 1) mutation as one of the primary molecular markers. Tumor protein 53 (p53) mutation is also closely associated with HGG. Aims and Objectives: The current study intended to ascertain the expression of IDH1 and P53 in patients with HGG and correlate that expression with clinical prognosis. Materials and Methods: The study included 34 patients with histopathological proven HGG. Relevant clinical information was recorded. The immunostaining results with anti-mouse monoclonal antibody for IDH 1 (R132H) and rabbit polyclonal antibody for p53 (RP 106-05) were statistically analyzed. Patients were followed up through telephone for a period of 1 year. Mortality within 1 year was regarded as a poor outcome. Results: About 85.29% (29/34) of the patients had Grade IV glioma, while only 14.71% (5/34) had Grade III glioma. Most patients with Grade III (3/5) (60.00%) and Grade IV (21/29) (72.41%) gliomas had p53 positivity. The majority of the patients with grade-III glioma (3/5) (60.00%) had IDH1 positivity, while most of the patients (23/29) (79.31%) with Grade IV gliomas had IDH1 negativity (P=0.0658). Age, gender, WHO grade, and adjuvant therapy did not show significant association with the outcome except for the p53 expression (P=0.0011*) and IDH1 expression (P=0.0025*). Correlation analysis showed a significant positive correlation between p53 makers with poor outcome (r=0.4781) and glioma grade (r=0.4028). Further, a negative yet insignificant correlation was recorded between IDH1 with age (r=-0.2285), p53 expression (r=-0.2568), and grade (r=-0.2988), although it showed a significant correlation with poor outcome (P=0.0001). Conclusion: p53-positive and IDH1-negative HGG had a significant correlation with the poor outcome. Thus, IDH1 and p53 are reliable markers for prognostication of HGG. [ABSTRACT FROM AUTHOR]

• Transfusion protocols, in order to reduce alloimmunization, are well applied and efficient. • The prevalence of G6PD deficiency in transfused red blood cell units is important. • The G6PD deficiency is only found in red blood cell units from African ancestry blood donors. Transfusion has a central place in the treatment of patients with sickle cell disease (SCD). Matching blood groups of red blood cell (RBC) units with the blood groups of the patient is essential to prevent alloimmunization and delayed hemolytic transfusion reaction. African ancestry donors have the best phenocompatibility with patients of the same origin, however their RBCs may present characteristic that can alter quality of the unit such as glucose-6-phosphate dehydrogenase (G6PD) deficiency. The objective is to analyze transfusion protocol, immunization rate and mismatch situations of SCD recipients and to evaluate the frequency of G6PD deficiency in RBCs units from African ancestry donors. Samples of units transfused to SCD patients were analyzed. Transfusion data were collected from institutional databases. The activity of G6PD was measured in the segment of the RBC units. A total of 98 segments of units transfused to 37 SCD recipients in 41 transfusions episodes was collected. Among patients, 35.1% (n = 13) had no antibodies; 10.8% (n = 4) had antibodies against Fya/Fyb, Jka/Jkb, M/N, S/s; 21.6% (n = 8) against RH/K antigens. In all cases, the protocols were in line with the recommendations. G6PD deficiency was observed in 9 units, that were all collected from Afro-Caribbean donors. The transfusion protocol is established to prevent immunological reactions due to disparities in blood group antigens between donors and SCD recipients. However, the units of African ancestry donors, which allowed the best compatibility, displayed a high rate of G6PD deficiency. The storage and recovery impact of this deficiency must be evaluated. [ABSTRACT FROM AUTHOR]

Introduction: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked hereditary disorder in southern China. However, the incidence rate of G6PD deficiency and the frequency of the most common G6PD gene variants vary widely. The purpose of this study was to investigate the prevalence, genotype, and phenotypic features of G6PD deficiency in neonates in Fujian province, southeastern China. Methods: This retrospective cohort study enrolled 2,789,002 newborns (1,521,431 males and 1,267,571 females) based on the newborn screening program for G6PD deficiency in Fujian Province between January 2010 and December 2021. Results: Of the 2,789,002 newborns enrolled, 26,437 cases were diagnosed (22,939 males and 3,498 females), and the estimated prevalence of G6PD deficiency in Fujian province was 0.95%. The prevalence was significantly higher among males (1.51%) than in females (0.28%) (p < 0.00001). Among the 3,198 patients with G6PD deficiency, 3,092 cases (2,145 males and 947 females) were detected to have G6PD gene variants. The top six prevalent genotypes identified represented 90.84% (2095/3,198) of the total and included c.1376G > T (44.93%), c.1388G > A (18.42%), c.1024C > T (9.32%), c.95A > G(8.69%), c.392G > T (5.25%), and c.871G > A (4.22%). The frequency of genotypes with c.1388G > A, c.1024C > T, and c.871G > A was higher in males in the Fujian province than in females, while the frequency of genotypes with c.1376G > T was lower. Furthermore, when comparing the enzyme activities of the top six prevalent genotypes, there were significant differences in the enzyme activities among the genotypes of male hemizygotes and female heterozygotes. According to the new classification of G6PD variants proposed by the World Health Organization (WHO), the variants with c.1376G > T, c.95A > G, and c.871G > A were recognized as Class A, while the c.392G > T, c.1388G > A, and c.1024C > T were recognized as Class B. Discussion: To the best of our knowledge, this study is the first to systematically describe the overview of epidemiological characteristics of newborn G6PD deficiency in Fujian province, China, including the screening rate, incidence rate, and variant spectrum. Additionally, we elucidated the relationship between the distribution of enzyme activity with specific mutations and their WHO classification patterns. Our results could provide strategies for screening, diagnosis, and genetic counseling of G6PD deficiency in this area. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To interrupt residual malaria transmission and achieve successful elimination of Plasmodium falciparum in low-transmission settings, the World Health Organization (WHO) recommends the administration of a single dose of 0.25 mg/kg (or 15 mg/kg for adults) primaquine (PQ) combined with artemisinin-based combination therapy (ACT), without glucose-6-phosphate dehydrogenase (G6PD) testing. However, due to the risk of haemolysis in patients with G6PD deficiency (G6PDd), PQ use is uncommon. Thus, this study aimed to assess the safety of a single low dose of PQ administered to patients with G6PD deficiency. Methods: An observational cohort study was conducted with patients treated for uncomplicated P. falciparum malaria with either single-dose PQ (0.25 mg/kg) (SLD PQ) + ACT or ACT alone. Microscopy-confirmed uncomplicated P. falciparum malaria patients visiting public health facilities in Arjo Didessa, Southwest Ethiopia, were enrolled in the study from September 2019 to November 2022. Patients with uncomplicated P. falciparum malaria were followed up for 28 days through clinical and laboratory diagnosis, such as measurements of G6PD levels and haemoglobin (Hb) concentrations. G6PD levels were measured by a quantiative CareSTART™ POCT S1 biosensor machine. Patient interviews were also conducted, and the type and frequency of clinical complaints were recorded. Hb data were taken on days (D) 7, 14, 21, and 28 following treatment with SLD-PQ + ACT or ACT alone. Results: A total of 249 patients with uncomplicated P. falciparum malaria were enrolled in this study. Of these, 83 (33.3%) patients received ACT alone, and 166 (66.7%) received ACT combined with SLD-PQ treatment. The median age of the patients was 20 (IQR 28–15) years. G6PD deficiency was found in 17 (6.8%) patients, 14 males and 3 females. There were 6 (7.2%) and 11 (6.6%) phenotypic G6PD-deficient patients in the ACT alone and ACT + SLD-PQ arms, respectively. The mean Hb levels in patients treated with ACT + SLD-PQ were reduced by an average of 0.45 g/dl (95% CI = 0.39 to 0.52) in the posttreatment phase (D7) compared to a reduction of 0.30 g/dl (95% CI = 0.14 to − 0.47) in patients treated with ACT alone (P = 0.157). A greater mean Hb reduction was observed on day 7 in the G6PDd ACT + SLD-PQ group (− 0.60 g/dL) than in the G6PDd ACT alone group (− 0.48 g/dL); however, there was no statistically significant difference (P = 0.465). Overall, D14 losses were 0.10 g/dl (95% CI = − 0.00 to 0.20) and 0.05 g/dl (95% CI = − 0.123 to 0.22) in patients with and without SLD-PQ, respectively (P = 0.412). Conclusions: This study's findings indicate that using SLD-PQ in combination with ACT is safe for uncomplicated P. falciparum malaria regardless of the patient's G6PD status in Ethiopian settings. Caution should be taken in extrapolating this finding in other settings with diverse G6DP phenotypes. [ABSTRACT FROM AUTHOR]

The evolution of classification of renal tumors has been impacted since the turn of the millennium by rapid progress in histopathology, immunohistochemistry, and molecular genetics. Together, these features have enabled firm recognition of specific, classic types of renal cell carcinomas, such as clear cell renal cell carcinoma, that in current practice trigger histologic-type specific management and treatment protocols. Now, the fifth Edition World Health Classification's new category of "Molecularly defined renal carcinomas" changes the paradigm, defining a total of seven entities based specifically on their fundamental molecular underpinnings. These tumors, which include TFE3 -rearranged, TFEB -altered, ELOC -mutated, fumarate hydratase-deficient, succinate dehydrogenase-deficient, ALK -rearranged, and SMARCB1 -deficient renal medullary carcinoma, encompass a wide clinical and histopathologic phenotypic spectrum of tumors. Already, important management aspects are apparent for several of these entities, while emerging therapeutic angles are coming into view. A brief, clinically-oriented introduction of the entities in this new category, focusing on relevant diagnostic, molecular, and management aspects, is the subject of this review. [ABSTRACT FROM AUTHOR]

Background: Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is an X‐linked recessive disorder that predisposes individuals to hemolysis due to an inborn error of metabolism. We performed a systematic literature review to evaluate G6PD deficiency as a possible etiology of nonimmune hydrops fetalis (NIHF) and severe fetal anemia. Methods: PubMed, OVID Medline, Scopus, and clinicaltrials.gov were queried from inception until 31 April 2023 for all published cases of NIHF and severe fetal anemia caused by G6PD deficiency. Keywords included "fetal edema," "hydrops fetalis," "glucose 6 phosphate dehydrogenase deficiency," and "fetal anemia." Cases with workup presuming G6PD deficiency as an etiology for NIHF and severe fetal anemia were included. PRISMA guidelines were followed. Results: Five cases of G6PD‐related NIHF and one case of severe fetal anemia were identified. Four fetuses (4/6, 66.7%) were male and two fetuses (2/6, 33.3%) were female. Mean gestational age at diagnosis of NIHF/anemia and delivery was 32.2 ± 4.9 and 35.7 ± 2.4 weeks, respectively. Four cases (66.7%) required a cordocentesis for fetal transfusion, and two cases (33.3%) received blood transfusions immediately following delivery. Among the four multigravida cases, two (50%) noted previous pregnancies complicated by neonatal anemia. When reported, the maternal cases included two G6PD deficiency carrier patients and two G6PD‐deficient patients. Exposures to substances known to cause G6PD deficiency‐related hemolysis occurred in 3/6 (50%) cases. Conclusion: Six cases of NIHF/severe fetal anemia were associated with G6PD deficiency. While G6PD deficiency is an X‐linked recessive condition, female fetuses can be affected. Fetal G6PD deficiency testing can be considered if parental history indicates, particularly if the standard workup for NIHF is negative. [ABSTRACT FROM AUTHOR]

Background and purpose: Pyruvate dehydrogenase complex deficiency is in up to 90% caused by pathogenic variants in the X‐linked PDHA1 gene. We aimed to investigate female relatives of index patients with PDHA1‐related disease to (i) describe the prevalence of female PDHA1 carriers, (ii) determine whether they had symptoms and signs, and (iii) delineate the associated phenotype. Methods: In a national population‐based study, we identified 37 patients with pathogenic variants in PDHA1. Sanger sequencing for the presence of the pathogenic variant was performed in their mothers and female relatives. The identified female carriers were clinically assessed, and their medical records were reviewed. Results: The proportion carrying a de novo variant was 86%. We identified seven female PDHA1 carriers from five families. Five of them exhibited clinical features of the disease and were previously undiagnosed; all had signs of peripheral axonal neuropathy, four presented with strokelike episodes including two with Leigh‐like lesions, and three had facial stigmata. Conclusions: PDHA1‐related disease is underrecognized in heterozygous female carriers. Peripheral axonal neuropathy, strokelike and Leigh‐like changes, and facial dysmorphism should raise suspicion of the disorder. Genetic analysis and clinical examination of potential female carriers are important for genetic counseling and have implications for treatment. [ABSTRACT FROM AUTHOR]

Background: Hepatitis A is a widespread viral infection with significant public health implications. Assessing glucose 6-phosphate dehydrogenase (G6PD) deficiency in hepatitis A patients is essential for various reasons, including prognosis, disease severity evaluation, encephalopathy risk identification, tailored management, and advancing scientific understanding. This study aimed to investigate the prevalence and clinical implications of G6PD impairment in individuals with fulminant hepatitis A. Methods: A cross-sectional descriptive analysis was conducted, involving hospitalized patients with fulminant hepatitis A. Demographic data, prevalence rates, and clinical findings were recorded in a database. The diagnosis of hepatitis A infection was confirmed using an anti-HAV IgM antibody test, and G6PD enzyme activity was measured with a fluorescent spot assay. Results: Out of 81 patients with hepatitis A, 57 (70.4%) were males, and 24 (29.5%) were females, with an average age of 24.6 years. Dark yellow urine and anorexia were the most common clinical symptoms. Notably, 30 (37%) patients lacked G6PD. The group with G6PD deficiency showed significantly higher rates of encephalopathy and mortality (P<0.01), along with elevated bilirubin (P=0.00), abnormal coagulation parameters, and low hemoglobin levels (P=0.00). Conclusion: In light of these findings, the present study proposes the implementation of routine G6PD level assessments and the evaluation of other relevant markers in regions where hepatitis A is endemic. Furthermore, the study underscores the need for vigilant monitoring of hemolysis and encephalopathy in affected patients to optimize clinical management and reduce morbidity and mortality associated with this condition. [ABSTRACT FROM AUTHOR]

The article examines a complex medical case involving a man with myelodysplastic syndrome who developed neutropenic fever, perianal pain, and jaundice shortly after a red blood cell transfusion. It discusses diagnostic challenges in identifying acute hemolysis as the cause of his symptoms, highlighting the role of clinical reasoning, laboratory tests like Lactate Dehydrogenase (LDH) and haptoglobin, and the management of Clostridium perfringens infection-induced hemolysis.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. G6PD is an essential enzyme in the pentose phosphate pathway (PPP), generating NADPH needed for cellular biosynthesis and reactive oxygen species (ROS) homeostasis, the latter especially key in red blood cells (RBCs). Beyond the RBC, there is emerging evidence that G6PD exerts an immunologic role by virtue of its functions in leukocyte oxidative metabolism and anabolic synthesis necessary for immune effector function. We review these here, and consider the global immunometabolic role of G6PD activity and G6PD deficiency in modulating inflammation and immunopathology. [ABSTRACT FROM AUTHOR]

Neurofibromatosis Type II (NFII) is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent Schwann cell tumors, as well as meningiomas and ependymomas. Unfortunately, few pharmacological options are available for NFII. Here, we undertake a genome-wide CRISPR/Cas9 screen to search for synthetic-lethal genes that, when inhibited, cause death of NF2 mutant Schwann cells but not NF2 wildtype cells. We identify ACSL3 and G6PD as two synthetic-lethal partners for NF2, both involved in lipid biogenesis and cellular redox. We find that NF2 mutant Schwann cells are more oxidized than control cells, in part due to reduced expression of genes involved in NADPH generation such as ME1. Since G6PD and ME1 redundantly generate cytosolic NADPH, lack of either one is compatible with cell viability, but not down-regulation of both. Since genetic deficiency for G6PD is tolerated in the human population, G6PD could be a good pharmacological target for NFII. Few therapeutic options are available for patients with Neurofibromatosis Type II. Here, the authors identify G6PD as a potential pharmacological target and show that NF2 mutant Schwann cells are in an oxidized state and die when G6PD is inhibited. [ABSTRACT FROM AUTHOR]

Background: With only one 15 mg primaquine tablet registered by a stringent regulatory authority and marketed, more quality-assured primaquine is needed to meet the demands of malaria elimination. Methods: A classic, two sequence, crossover study, with a 10-day wash out period, of 15 mg of IPCA-produced test primaquine tablets and 15 mg of Sanofi reference primaquine tablets was conducted. Healthy volunteers, aged 18–45 years, without glucose-6-phosphate dehydrogenase deficiency, a baseline haemoglobin ≥ 11 g/dL, creatinine clearance ≥ 70 mL/min/1.73 ms, and body mass index of 18.5–30 kg/m2 were randomized to either test or reference primaquine, administered on an empty stomach with 240 mL of water. Plasma primaquine and carboxyprimaquine concentrations were measured at baseline, then 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.333, 2.667, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0 and 72.0 h by liquid chromatography coupled to tandem mass spectrometry. Primaquine pharmacokinetic profiles were evaluated by non-compartmental analysis and bioequivalence concluded if the 90% confidence intervals (CI) of geometric mean (GM) ratios of test vs. reference formulation for the peak concentrations (Cmax) and area under the drug concentration–time (AUC0–t) were within 80.00 to 125.00%. Results: 47 of 50 volunteers, median age 33 years, completed both dosing rounds and were included in the bioequivalence analysis. For primaquine, GM Cmax values for test and reference formulations were 62.12 vs. 59.63 ng/mL, resulting in a GM ratio (90% CI) of 104.17% (96.92–111.96%); the corresponding GM AUC0–t values were 596.56 vs. 564.09 ngxh/mL, for a GM ratio of 105.76% (99.76–112.08%). Intra-subject coefficient of variation was 20.99% for Cmax and 16.83% for AUC0–t. Median clearances and volumes of distribution were similar between the test and reference products: 24.6 vs. 25.2 L/h, 189.4 vs. 191.0 L, whilst the median half-lives were the same, 5.2 h. Conclusion: IPCA primaquine was bioequivalent to the Sanofi primaquine. This opens the door to prequalification, registration in malaria endemic countries, and programmatic use for malaria elimination. Trial registration The trial registration reference is ISRCTN 54640699 [ABSTRACT FROM AUTHOR]

The presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency may increase the risk of type 2 diabetes mellitus (T2DM), with differing prevalence between males and females. Although G6PD deficiency is an X-linked genetic condition, its interaction with sex regarding T2DM risk among the Taiwanese population has not been fully explored. This study aimed to investigate the association between G6PD deficiency and T2DM risk in the Taiwanese population, focusing on the potential influence of sex. Data were obtained from the Taiwan Biobank (TWB) database, involving 85,334 participants aged 30 to 70 years. We used multiple logistic regression analysis to assess the interaction between G6PD rs72554664 and sex in relation to T2DM risk. The T2DM cohort comprised 55.35% females and 44.65% males (p < 0.001). The TC + TT genotype of rs72554664 was associated with an increased risk of T2DM, with an odds ratio (OR) of 1.95 (95% CI: 1.39–2.75), and males showed an OR of 1.31 (95% CI: 1.19–1.44). Notably, the G6PD rs72554664-T allelic variant in hemizygous males significantly elevated the T2DM risk (OR), 4.57; p < 0.001) compared to females with the CC genotype. Our findings suggest that the G6PD rs72554664 variant, in conjunction with sex, significantly affects T2DM risk, particularly increasing susceptibility in males. The association of the G6PD rs72554664-T allelic variant with a higher risk of T2DM highlights the importance of sex-specific mechanisms in the interplay between G6PD deficiency and T2DM. [ABSTRACT FROM AUTHOR]

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 approximately 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. [ABSTRACT FROM AUTHOR]

This letter discusses a case of methemoglobinemia caused by sodium nitrite poisoning. The patient exhibited symptoms such as coma, cyanosis, desaturation, and hypotension. The blood gas analyzer used in the emergency department was unable to accurately measure hemoglobin concentration and saturation, which hindered the diagnosis and treatment of the patient. The letter also describes in vitro experiments that were conducted to understand why the analyzer failed to measure methemoglobin levels. The results suggest that the analyzer had difficulty reporting methemoglobin levels accurately, and clinicians should be aware of this issue when treating patients with methemoglobinemia. [Extracted from the article]

Background Plasmodium vivax presents a significant challenge for malaria elimination in the Greater Mekong Subregion. We evaluated the effectiveness of primaquine for reducing relapses of vivax malaria. Methods Patients with uncomplicated P vivax malaria from eastern Myanmar received chloroquine (25-mg base/kg given in 3 days) plus unsupervised PQ (0.25 mg/kg/d for 14 days) without screening for glucose-6-phosphate dehydrogenase deficiency and were followed for a year. Results A total of 556 patients were enrolled to receive the chloroquine/primaquine treatment from February 2012 to August 2013. During the follow-up, 38 recurrences were detected, presenting a cumulative recurrence rate of 9.1% (95% CI, 4.1%–14.1%). Genotyping at the pvmsp1 and pvmsp3α loci by amplicon deep sequencing and model prediction indicated that 13 of the 27 recurrences with genotyping data were likely due to relapses. Notably, all confirmed relapses occurred within the first 6 months. Conclusions The unsupervised standard dose of primaquine was highly effective as a radical cure for P vivax malaria in eastern Myanmar. The high presumed effectiveness might have benefited from the health messages delivered during the enrollment and follow-up activities. Six-month follow-ups in the Greater Mekong Subregion are sufficient for detecting most relapses. [ABSTRACT FROM AUTHOR]

A single 300 mg dose of tafenoquine (an 8-aminoquinoline), in combination with a standard 3-day course of chloroquine, is approved in several countries for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged ≥ 16 years. Despite this, questions have arisen on the optimal dose of tafenoquine. Before the availability of tafenoquine, a 3-day course of chloroquine in combination with the 8-aminoquinoline primaquine was the only effective radical cure for vivax malaria. The World Health Organization (WHO)-recommended standard regimen is 14 days of primaquine 0.25 mg/kg/day or 7 days of primaquine 0.5 mg/kg/day in most regions, or 14 days of primaquine 0.5 mg/kg/day in East Asia and Oceania, however the long treatment courses of 7 or 14 days may result in poor adherence and, therefore, low treatment efficacy. A single dose of tafenoquine 300 mg in combination with a 3-day course of chloroquine is an important advancement for the radical cure of vivax malaria in patients without glucose-6-phosphate dehydrogenase (G6PD) deficiency, as the use of a single-dose treatment will improve adherence. Selection of a single 300 mg dose of tafenoquine for the radical cure of P. vivax malaria was based on collective efficacy and safety data from 33 studies involving more than 4000 trial participants who received tafenoquine, including over 800 subjects who received the 300 mg single dose. The safety profile of single-dose tafenoquine 300 mg is similar to that of standard-dosage primaquine 0.25 mg/kg/day for 14 days. Both primaquine and tafenoquine can cause acute haemolytic anaemia in individuals with G6PD deficiency; severe haemolysis can lead to anaemia, kidney damage, and, in some cases, death. Therefore, relapse prevention using an 8-aminoquinoline must be balanced with the need to avoid clinical haemolysis associated with G6PD deficiency. To minimize this risk, the WHO recommends G6PD testing for all individuals before the administration of curative doses of 8-aminoquinolines. In this article, the authors review key efficacy and safety data from the pivotal trials of tafenoquine and argue that the currently approved dose represents a favourable benefit–risk profile. [ABSTRACT FROM AUTHOR]

Background: Plasmodium vivax relapses due to dormant liver hypnozoites can be prevented with primaquine. However, the dose must be adjusted in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. In French Guiana, assessment of G6PD activity is typically delayed until day (D)14 to avoid the risk if misclassification. This study assessed the kinetics of G6PD activity throughout P. vivax infection to inform the timing of treatment. Methods: For this retrospective monocentric study, data on G6PD activity between D1 and D28 after treatment initiation with chloroquine or artemisinin-based combination therapy were collected for patients followed at Cayenne Hospital, French Guiana, between January 2018 and December 2020. Patients were divided into three groups based on the number of available G6PD activity assessments: (i) at least two measurements during the P. vivax malaria infection; (ii) two measurements: one during the current infection and one previously; (iii) only one measurement during the malaria infection. Results: In total, 210 patients were included (80, 20 and 110 in groups 1, 2 and 3, respectively). Data from group 1 showed that G6PD activity remained stable in each patient over time (D1, D3, D7, D14, D21, D28). None of the patients with normal G6PD activity during the initial phase (D1–D3) of the malaria episode (n = 44) was categorized as G6PD-deficient at D14. Patients with G6PD activity < 80% at D1 or D3 showed normal activity at D14. Sex and reticulocyte count were statistically associated with G6PD activity variation. In the whole sample (n = 210), no patient had severe G6PD deficiency (< 10%) and only three between 10 and 30%, giving a G6PD deficiency prevalence of 1.4%. Among the 100 patients from group 1 and 2, 30 patients (26.5%) were lost to follow-up before primaquine initiation. Conclusions: In patients treated for P. vivax infection, G6PD activity did not vary over time. Therefore, G6PD activity on D1 instead of D14 could be used for primaquine dose-adjustment. This could allow earlier radical treatment with primaquine, that could have a public health impact by decreasing early recurrences and patients lost to follow-up before primaquine initiation. This hypothesis needs to be confirmed in larger prospective studies. [ABSTRACT FROM AUTHOR]

Water-soluble vitamins play an essential coenzyme role in the nervous system. Acquired vitamin deficiencies are easily treatable, however, without treatment, they can lead to irreversible complications. This study aimed to provide clinical, laboratory parameters and neuroimaging data on vitamin deficiencies in an attempt to facilitate early diagnosis and prompt supplementation. From July 1998 to July 2023, patients at Necker-Enfants-Malades Hospital presenting with acute neurological symptoms attributed to acquired vitamin deficiency were included. Clinical data were extracted from Dr Warehouse database. Neuroimaging, biochemical and electrophysiological data were reviewed. Patients with vitamin B1 deficiency exhibited abnormal eye movements (n = 4/4), fluctuations in consciousness (n = 3/4), and ataxia (n = 3/4). Brain MRI showed alterations of fourth ventricle region (n = 4/4), periaqueductal region (n = 4/4), tectum (n = 3/4), and median thalami (n = 3/4). Patients with vitamin B2 deficiency presented with early onset hypotonia (n = 3/4), hyperlactatemia (n = 4/4), and hyperammonemia (n = 4/4). Plasma acylcarnitines revealed a multiple acyl-coA dehydrogenase deficiency-like profile (n = 4/4). In vitamin B12 deficiency, young children presented with developmental delay (n = 7/7) and older children with proprioceptive ataxia (n = 3/3). Brain MRI revealed atrophy (n = 7/7) and spinal MRI hyperintensity in posterior cervical columns (n = 3/3). Metabolic findings showed elevated methylmalonic acid (n = 6/7) and hyperhomocysteinemia (n = 6/7). Patients with vitamin C deficiency exhibited gait disturbances and muscle weakness (n = 2/2). Acquired vitamin deficiencies may display reversible clinical symptoms mimicking inherited metabolic disorders. Some situations raise suspicion for diagnosis: concordant clinical presentation, suggestive neuroimaging findings, and/or biochemical evidence. Any acute neurological condition should be treated without waiting for definitive biochemical confirmation. • Although they are not extensively documented, vitamin deficiencies do occur in children. • Acquired vitamin deficiencies are easily treatable but without treatment, can lead to irreversible neurological complications. • One should consider a vitamin deficiency in the presence of unexplained neurological symptoms. • One should consider a vitamin deficiency in an exclusively breastfed infant showing signs of developmental stagnation. • Initiation vitamin supplementation should not be delayed pending conclusive biochemical confirmation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Mutations in succinate dehydrogenase (SDH) and fumarate hydratase (FH) give rise to various familial cancer syndromes, with these alterations being characteristic of certain types of histomorphologically specific leiomyomas that hold significant predictive value. Materials and Methods: This study presents two cases of uterine leiomyomas exhibiting rare histomorphological and genetic characteristics, which are crucial for prognosis and further treatment. Results: Distinct histopathological features such as marked nuclear atypia, intracellular eosinophilic globules, and abnormal intratumoral vessels raise suspicion for specific leiomyoma subtypes, which carry predictive significance for additional hereditary cancer syndromes. Immunohistochemical analysis confirmed FH/SDH deficiency in both patients, who underwent careful follow-up. Conclusions: This study describes two cases involving unusual leiomyomas, the histopathological characteristics of which may easily go unrecognized. These features hold predictive significance because their specific mutations point to additional hereditary cancer syndromes, highlighting the need for further examinations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A DPD deficiency should be considered in case of severe toxicity even in the absence of common risk variants in DPYD. [ABSTRACT FROM AUTHOR]

Background: Glucose 6 Phosphate Dehydrogenase deficiency is the most common erythrocyte enzymopathy being present in more than 400 million people worldwide which presents in the neonatal period as unconjugated hyperbilirubinemia and is inherited as an X-linked recessive disorder. G6PD enzyme deficiency leads to impaired production of reduced glutathione and predisposes the red blood cells to damage by oxidative metabolites causing haemolysis. Deficient neonates may manifest clinically as indirect hyperbilirubinemia or even kernicterus. Methods: This prospective observational study was conducted in Neonatal Intensive Care Unit, Gauhati Medical College and Hospital, over a period of one year from December 2022 to November 2023. A total number of 320 neonates with hyperbilirubinemia were included in this study. Data collection was done by history taking, meticulous clinical examination and essential laboratory tests. Results: Physiological jaundice was found to be the most common cause of neonatal hyperbilirubinemia (59.6 %) followed by ABO incompatibility (22.5%). G6PD deficiency was found in 5.6 % of neonates. The sex distribution was male 198 (61.9%) and female 122 (38.1%). The total serum bilirubin in G6PD deficient groups was found to be significantly higher (Mean 21.06 mg/dl) than due to other causes (Mean 18.2mg/dl). Conclusion: WHO recommends population screening in regions where the prevalence of G6PD deficiency is 3-5% or more, but this has yet to become routine practice in many parts of India. It is well known that hemoglobinopathies are common among people of Assam. Hence screening for G6PD deficiency in neonatal jaundice may be adopted as a non-mandatory screening test in Assam, especially in case of severe neonatal hyperbilirubinemia. Further, diagnosis of G6PD deficiency status also helps in prevention of future hemolysis due to exposure to offending agents. [ABSTRACT FROM AUTHOR]

Objective: This study aims to elucidate the long‐term benefit of newborn screening (NBS) for individuals with long‐chain 3‐hydroxy‐acyl‐CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiency, inherited metabolic diseases included in NBS programs worldwide. Methods: German national multicenter study of individuals with confirmed LCHAD/MTP deficiency identified by NBS between 1999 and 2020 or selective metabolic screening. Analyses focused on NBS results, confirmatory diagnostics, and long‐term clinical outcomes. Results: Sixty‐seven individuals with LCHAD/MTP deficiency were included in the study, thereof 54 identified by NBS. All screened individuals with LCHAD deficiency survived, but four with MTP deficiency (14.8%) died during the study period. Despite NBS and early treatment neonatal decompensations (28%), symptomatic disease course (94%), later metabolic decompensations (80%), cardiomyopathy (28%), myopathy (82%), hepatopathy (32%), retinopathy (17%), and/or neuropathy (22%) occurred. Hospitalization rates were high (up to a mean of 2.4 times/year). Disease courses in screened individuals with LCHAD and MTP deficiency were similar except for neuropathy, occurring earlier in individuals with MTP deficiency (median 3.9 vs. 11.4 years; p = 0.0447). Achievement of dietary goals decreased with age, from 75% in the first year of life to 12% at age 10, and consensus group recommendations on dietary management were often not achieved. Interpretation: While NBS and early treatment result in improved (neonatal) survival, they cannot reliably prevent long‐term morbidity in screened individuals with LCHAD/MTP deficiency, highlighting the urgent need of better therapeutic strategies and the development of disease course‐altering treatment. [ABSTRACT FROM AUTHOR]

Subcorneal pustular dermatosis (SPD) is a rare neutrophilic dermatosis characterized by pustules on the trunk and intertriginous areas. While oral dapsone is the first-line treatment for SPD, alternative options are necessary for patients with glucose-6-phosphate dehydrogenase deficiency, drug hypersensitivity reactions, or refractory disease. To date, no consensus exists regarding next-best agents for SPD. In this report, we present a patient with significant SPD who developed dapsone hypersensitivity syndrome and then was successfully treated with colchicine and adalimumab. We propose that colchicine should be considered as a second-line treatment for SPD and present a therapeutic algorithm for clinicians to utilize when patients are not candidates for dapsone, have side effects requiring drug discontinuation, or have refractory disease. [ABSTRACT FROM AUTHOR]

The primary objectives of the study were (a) to confirm that glucose 6-phosphate dehydrogenase (G6PD) deficiency affects HbA1c values in a sample of children and adolescents with type 1 diabetes (T1D) and (b) to quantify this effect so that a correction can be applied to the HbA1c values found in current clinical practice. The following data were collected: age, sex, G6PD, number of daily capillary blood glucose measurements, 90-day average blood glucose levels prior to the study, HbA1c, and glycated hemoglobin estimated (eA1c) obtained from blood glucose levels. Patients were divided into three groups based on G6PD values: deficient, intermediate, and nondeficient. In each group, a comparison between the average eA1C and HbA1c values was performed. Then, the difference between the eA1c and HbA1c values of each patient and the mean of the differences (MD) of all patients was calculated within the three groups. Finally, a comparison of the MD values between groups was performed. Seventy-four subjects with T1D were studied. Based on the G6PD value, 33 subjects were deficient, 8 were intermediate, and 33 subjects were nondeficient. In deficient patients, the eA1c values were significantly higher than the HbA1c values. In the other two groups, however, there were no differences. The MD values between the three groups were significantly different. In deficient patients, MD values were higher than those in intermediate and in nondeficient patients. No difference was found between intermediate and nondeficient subjects. Our study confirms that G6PD deficiency affects HbA1c values in children and adolescents with T1D, both in deficient subjects and, to a much lesser extent, in intermediate subjects. In deficient subjects, there is an average reduction in HbA1c attributable to enzyme deficiency of 1.3% (14 mmol/mol) and in intermediate subjects of 0.3% (3 mmol/mol). [ABSTRACT FROM AUTHOR]