Glucose-6-phosphate Dehydrogenase Deficiency Research Articles

G6PD gene detection in neonatal hyperbilirubinemia and analysis of related risk factors.

Hyperbilirubinemia is a common disorder in neonates, with premature infants at higher risk of developing the disorder. Glucose-6-phosphate dehydrogenase (G6PD) gene detection was used to determine the incidence of G6PD deficiency and analyze the etiologies of G6PD deficiency in neonates with hyperbilirubinemia in the Zunyi region with the aim of providing scientific evidence for the clinical diagnosis and treatment. For the gene detection, 64 neonates with hyperbilirubinemia were selected as the observation group and 30 normal neonates were selected as the control group, and the risk factors for hyperbilirubinemia were investigated by using multivariate logistic regression analysis. Among the neonates in the observation group, 59 cases had the G1388A mutation (92.19%) and 5 cases had the G1376T mutation (7.81%). No mutation was detected in the control group. In the observation group, the proportion of neonates who were born prematurely, with artificial feeding, with the age of starting feeding of more than 24 h, the time of first bowel movement of more than 24 h, premature rupture of membranes, infection, scalp hematoma, and perinatal asphyxia was higher than that in the control group, and the difference was statistically significant (p< 0.05). Multivariate logistic regression analysis showed that prematurity, infection, scalp hematoma, perinatal asphyxia, the age of starting feeding of more than 24 h, and the time of first bowel movement over 24 h were risk factors for the development of neonatal hyperbilirubinemia (p< 0.05). The G1338A and G1376T mutations were important features of the genetics of neonatal hyperbilirubinemia, and genetic detection together with the prevention of prematurity, infection, scalp hematoma, perinatal asphyxia, the age of starting feeding, and the time of first bowel movement would help reduce the incidence of this disease.

Inheritance of Hb S and G6PD deficiency in a familiar group.

Inheritance of Hb S and G6PD deficiency in a familiar group.

TREATMENT FOR MALARIA PATIENTS IN PAKISTAN AND THE PREDOMINANCE OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY

Even though it predisposes carriers to hemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency is linked with malaria endemicity. This fact supports the malaria prevention theory. The objective of this paper to determine whether and how much there is a protective relationship between malaria and G6PD deficiency. Twelve databases were searched for studies describing any G6PD connection in malaria patients. 38 of the 50 included papers qualified for the review. Results indicated that there was no harmful association between G6PD deficiency and uncomplicated falciparum malaria in Even though it puts carriers at risk for hemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency is widespread in areas of Pakistan where malaria is also prevalent. This data supports the malaria protection hypothesis. Pakistan's annual malaria burden is estimated to be 1.5 million cases. The government needs to execute a successful malaria control and eradication program, given the prevailing circumstances. Destroying Plasmodium falciparum gametocytes and eradicating Plasmodium vivax hypnozoite reservoirs are possible with primaquine. However, when using this medication, those who lack the enzyme glucose-6-phosphate (G6PD) experience hemolysis. The distribution of malaria and G6PD deficiency in Pakistan must be mapped to create an effective medication to suppress the disease. No significant reports of G6PD deficiency (G6PDd) in malaria patients have come from Pakistan. This review article seeks to establish the existence and magnitude of a protective connection between malaria and G6PD deficiency

An Unusual Presentation of Glucose Six Phosphate Dehydrogenase Deficiency in a Toddler: A Case Report

ABSTRACT Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common worldwide inherited red cell enzymopathy which may have a varied presentation. It usually comes to attention when exposed to oxidative agents leads to an acute hemolytic crisis with a sudden dip in hemoglobin levels. G6PD deficiency may also present as neonatal jaundice. Respiratory distress is an unusual presentation of G6PD deficiency especially when a respiratory infection is ruled out. We hereby present a case of G6PD deficiency in an 18-month-old toddler who presented with an acute hemolytic crisis with respiratory distress. The myriad of symptoms of G6PD deficiency must be kept in mind, and it is important that caution be exercised while prescribing oxidative drugs to patients with G6PD deficiency.

Study of the antigenic characteristics of red blood cells units and their sickle cell disease recipients and the G6PD activity of transfused red blood cells units

IntroductionTransfusion 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. MethodsSamples 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. ResultsA 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. ConclusionThe 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.

Functional neutrophil disorders: Chronic granulomatous disease and beyond.

Since their description by Metchnikoff in 1905, phagocytes have been increasingly recognized to be the entities that traffic to sites of infection and inflammation, engulf and kill infecting organisms, and clear out apoptotic debris all the while making antigens available and accessible to the lymphoid organs for future use. Therefore, phagocytes provide the gateway and the first check in host protection and immune response. Disorders in killing and chemotaxis lead not only to infection susceptibility, but also to autoimmunity. We aim to describe chronic granulomatous disease and the leukocyte adhesion deficiencies as well as myeloperoxidase deficiency and G6PD deficiency as paradigms of critical pathways.

Biallelic hexokinase 1 (HK1) variants causative of non-spherocytic haemolytic anaemia: A case series with emphasis on the HK1 promoter variant and literature review.

The hexokinase (HK) enzyme plays a key role in red blood cell energy production. Hereditary non-spherocytic haemolytic anaemia (HNSHA) caused by HK deficiency is a rare disorder with only 12 different disease-associated variants identified. Here, we describe the clinical features and genotypes of four previously unreported patients with hexokinase 1 (HK1)-related HNSHA, yielding two novel truncating HK1 variants. The patients' phenotypes varied from mild chronic haemolytic anaemia to severe infantile-onset transfusion-dependent anaemia. Three of the patients had mild haemolytic disease caused by the common HK1 promoter c.-193A>G variant combined with an intragenic HK1 variant, emphasizing the importance of including this promoter variant in the haemolytic disease gene panels. HK activity was normal in a severely affected patient with a homozygous HK1 c.2599C>T, p.(His867Tyr) variant, but the affinity for ATP was reduced, hampering the HK function. In cases of HNSHA, kinetic studies should be considered in the functional studies of HK. We reviewed the literature of previously published patients to provide better insight into this rare disease and add to the understanding of genotype-phenotype correlation.

Antioxidant activity and levels of lipid peroxidation in glucose -6- phosphate deficient neonates

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic abnormality that results in inadequate amount of this all important protein that help regulate key physiological processes in the body. This study was carried out to evaluate plasma activity of antioxidants and level of lipid peroxidation in neonates with G6PD deficiency. A total of forty neonates delivered at Wesley Guide Hospital, Ilesa, Osun State were used for this study. They were divided into two groups; group 1 consists of 20 G6PD deficient neonates as the test while group2 consists of 20 G6PD positive neonates as control. 5mls of venous blood was taken from both test and control and prepared to obtain the plasma. The plasma was stored at room temperature prior analysis. The plasma activity of antioxidant enzyme [superoxide dismutase, catalase, glutathione, glutathione peroxidase (Gpx)], non-enzymatic antioxidant (vitamin E, vitamin C, beta-carotene) and plasma level of malonyldialdehyde (MDA) was carried out in both test and control using standard methods. The results of the study revealed no significant difference (p&lt;0.05) in the plasma activity of most of the antioxidant enzymes with the exception of GPx which was significantly raised in the test subjects when compared with the control.. However, the plasma activity of both vitamin C and beta-carotene increased significantly (p&lt;0.05) in the test when compared with the control. The plasma level of MDA was also significantly raised in the test when compared with the control group. This study revealed the presence of lipid peroxidation and possibly oxidative stress in G6PD deficient neonates.

Computational analysis of dimer G6PD structure to elucidate pathogenicity of G6PD variants.

An inherent genetic enzyme disorder in humans, known as glucose-6-phosphate dehydrogenase (G6PD) deficiency, arises due to specific mutations. While the prevailing approach for investigating G6PD variants involves biochemical analysis, the intricate structural details remain limited, impeding a comprehensive understanding of how different G6PD variants of varying classes impact their functionality. This study 22 examined the dynamic properties of G6PD wild types and six G6PD variants from 23 different classes using molecular dynamic simulation (MDS). The wild-type and variant 24 G6PD structures unveil high fluctuations within the amino acid range of 274-515, the structural NADP+ binding site, pivotal for enzyme dimerization. Specifically, two variants, G6PDZacatecas (R257L) and G6PDDurham (K238R), demonstrate compromised structural stability at the dimer interface, attributable to the disruption of a salt bridge involving Glu 206 and Lys 407, along with the disturbance of hydrogen bonds formed by Asp 421 at the βN-βN sheets. Consequently, this impairment cascades to affect the binding affinity of crucial interactions, such as Lys 171-Glucose-6-Phosphate (G6P) and Lys 171-catalytic NADP+, leading to diminished enzyme activity. This study underscores the utility of computational in silico techniques in predicting the structural alterations and flexibility of G6PD variants. This insight holds promise for guiding future endeavors in drug development targeted at mitigating the impacts of G6PD deficiency.

The Impact of G6PD Deficiency on Liver Function in Children Under 15

Glucose-6-phosphate dehydrogenase (G6PD) is involved in the first phase of the pentose phosphate pathway (PPP), entailing the reduction of nicotinamide adenine dinucleotide phosphate (NADP+) and the oxidation of glucose-6-phosphate to 6-phosphogluconolactone. A deficiency in the G6PD activity can result in numerous illnesses, including liver diseases. The first three enzymes in PPP are responsible for the oxidative phase. They make NADPH, which is needed to deal with oxidative stress, especially in people who do not have enough G6PD. The study included (90) samples from people with hemolytic anemia (Favzim) and control to determine the levels of G6PD, albumin, total protein, liver function, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and bilirubin. The results showed that there was a significant decrease (P&lt;0.05) in the serum levels of G6PD in the patients group when compared with the control group. Also, there was a significant increase (P&lt;0.05) in the serum levels of albumin, total protein, ALP, ALT, AST and total bilirubin in patients with the G6PD deficiency when compared with the control group. In addition, this study revealed a strong positive correlation between some biochemical parameters studied, such as: Total protein with TSB (r2 = 0.897), TSB with ALT (r2 = 0.893), AST with ALT (r2 = 0.623) and total protein with ALT (r2 = 0.804).

Radical cure for Plasmodium vivax malaria after G6PD qualitative testing in four provinces in Cambodia, results from Phase I implementation

BackgroundCambodia aims to eliminate all forms of malaria by 2025. In 2020, 90% of all malaria cases were Plasmodium vivax. Thus, preventing P. vivax and relapse malaria is a top priority for elimination. 14-day primaquine, a World Health Organization-recommended radical cure treatment regimen, specifically targets dormant hypnozoites in the liver to prevent relapse. Cambodia introduced P. vivax radical cure with primaquine after glucose-6-phosphate dehydrogenase (G6PD) qualitative testing in 2019. This paper presents Cambodia’s radical cure Phase I implementation results and assesses the safety, effectiveness, and feasibility of the programme prior to nationwide scale up.MethodsPhase I implementation was carried out in 88 select health facilities (HFs) across four provinces. Males over 20kgs with confirmed P. vivax or mixed (P. vivax and Plasmodium falciparum) infections were enrolled. A descriptive analysis evaluated the following: successful referral to health facilities, G6PD testing results, and self-reported 14-day treatment adherence. P. vivax incidence was compared before and after radical cure rollout and a controlled interrupted time series analysis compared the estimated relapse rate between implementation and non-implementation provinces before and after radical cure.ResultsIn the 4 provinces from November 2019 to December 2020, 3,239 P. vivax/mixed infections were reported, 1,282 patients underwent G6PD deficiency testing, and 959 patients received radical cure, achieving 29.6% radical cure coverage among all P. vivax/mixed cases and 98.8% coverage among G6PD normal patients. Among those who initiated radical cure, 747 patients (78%) completed treatment. Six patients reported side effects. In implementation provinces, an average 31.8 relapse cases per month were estimated signaling a 90% (286 cases) reduction in relapse compared to what would be expected if radical cure was not implemented.ConclusionsPlasmodium vivax radical cure is a crucial tool for malaria elimination in Cambodia. The high coverage of radical cure initiation and adherence among G6PD normal patients demonstrated the high feasibility of providing radical cure at point of care in Cambodia. Incomplete referral from community to HFs and limited capacity of HF staff to conduct G6PD testing in high burden areas led to lower coverage of G6PD testing. Phase I implementation informed approaches to improve referral completion and patient adherence during the nationwide expansion of radical cure in 2021.

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.

The effect of glucose-6-phosphate dehydrogenase deficiency on allogeneic hematopoietic stem cell transplantation in patients with hematological disorders

Objectives: To determine the effect of glucose-6-phosphate-dehydrogenase (G6PD) deficiency on patients' complications and prognosis following allogeneic stem cell hematopoietic transplantation (allo-HSCT) . Methods: 7 patients with G6PD deficiency (study group) who underwent allo-HSCT at Peking University People's Hospital from March 2015 to January 2021 were selected as the study group, and thirty-five patients who underwent allo-HSCT during the same period but did not have G6PD deficiency were randomly selected as the control group in a 1∶5 ratio. Gender, age, underlying diseases, and donors were balanced between the two groups. Collect clinical data from two patient groups and perform a retrospective nested case-control study. Results: The study group consisted of six male patients and one female patient, with a median age of 37 (range, 2-45) years old. The underlying hematologic diseases included acute myeloid leukemia (n=3), acute lymphocytic leukemia (n=2), and severe aplastic anemia (n=2). All 7 G6PD deficiency patients achieved engraftment of neutrophils within 28 days of allo-HSCT, while the engraftment rate of neutrophils was 94.5% in the control group. The median days of platelet engraftment were 21 (6-64) d and 14 (7-70) d (P=0.113). The incidence rates of secondary poor graft function in the study group and control group were 42.9% (3/7) and 8.6% (3/35), respectively (P=0.036). The CMV infection rates were 71.4% (5/7) and 31.4% (11/35), respectively (P=0.049). The incidence rates of hemorrhagic cystitis were 57.1% (4/7) and 8.6% (3/35), respectively (P=0.005), while the bacterial infection rates were 100% (7/7) and 77.1% (27/35), respectively (P=0.070). The infection rates of EBV were 14.3% (1/7) and 14.3% (5/35), respectively (P=1.000), while the incidence of fungal infection was 14.3% (1/7) and 25.7% (9/35), respectively (P=0.497). The rates of post-transplant lymphoproliferative disease (PTLD) were 0% and 5.7%, respectively (P=0.387) . Conclusions: The findings of this study indicate that blood disease patients with G6PD deficiency can tolerate conventional allo-HSCT pretreatment regimens, and granulocytes and platelets can be implanted successfully. However, after transplantation, patients should exercise caution to avoid viral infection, complications of hemorrhagic cystitis, and secondary poor graft function.

Primaquine in glucose-6-phosphate dehydrogenase deficiency: an adaptive pharmacometric assessment of ascending dose regimens in healthy volunteers

Background:Primaquine is an 8-aminoquinoline antimalarial. It is the only widely available treatment to prevent relapses of Plasmodium vivax malaria. The 8-aminoquinolines cause dose-dependent haemolysis in glucose-6-phosphate dehydrogenase deficiency (G6PDd). G6PDd is common in malaria endemic areas but testing is often not available. As a consequence primaquine is underused.Methods:We conducted an adaptive pharmacometric study to characterise the relationship between primaquine dose and haemolysis in G6PDd. The aim was to explore shorter and safer primaquine radical cure regimens compared to the currently recommended 8-weekly regimen (0.75 mg/kg once weekly), potentially obviating the need for G6PD testing. Hemizygous G6PDd healthy adult Thai and Burmese male volunteers were admitted to the Hospital for Tropical Diseases in Bangkok. In Part 1, volunteers were given ascending dose primaquine regimens whereby daily doses were increased from 7.5 mg up to 45 mg over 15–20 days. In Part 2 conducted at least 6 months later, a single primaquine 45 mg dose was given.Results:24 volunteers were enrolled in Part 1, and 16 in Part 2 (13 participated in both studies). In three volunteers, the ascending dose regimen was stopped because of haemolysis (n=1) and asymptomatic increases in transaminases (n=2; one was hepatitis E positive). Otherwise the ascending regimens were well tolerated with no drug-related serious adverse events. In Part 1, the median haemoglobin concentration decline was 3.7 g/dL (range: 2.1–5.9; relative decline of 26% [range: 15–40%]). Primaquine doses up to 0.87 mg/kg/day were tolerated subsequently without clinically significant further falls in haemoglobin. In Part 2, the median haemoglobin concentration decline was 1.7 g/dL (range 0.9–4.1; relative fall of 12% [range: 7–30% decrease]). The ascending dose primaquine regimens gave seven times more drug but resulted in only double the haemoglobin decline.Conclusions:In patients with Southeast Asian G6PDd variants, full radical cure treatment can be given in under 3 weeks compared with the current 8-week regimen.Funding:Medical Research Council of the United Kingdom (MR/R015252/1) and Wellcome (093956/Z/10/C, 223253/Z/21/Z).Clinical trial number:Thai Clinical Trial Registry: TCTR20170830002 and TCTR20220317004.

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

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. 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. 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. 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.

Newborn screening and diagnosis for Glucose-6-phosphate dehydrogenase deficiency at Danang Hospital for Women and Children

Background: G6PD deficiency can result in acute hemolysis anemia during times of increased reactive oxygen species production. This study aimed to investigate the rate of high risk among newborns who were screened for G6PD deficiency, as well as some clinical characteristics of those who had this disease at Da Nang Hospital for Women and Children. Materials and Methods: 10,020 newborns were screened for G6PD deficiency using dried heel blood spots,. Samples of peripheral venous blood is drawn from high-risk infants for diagnostic testing. Results: The proportion of high-risk newborns was 1.12%, with boys having a greater incidence than girls (1.71% versus 0.48%). G6PD activity was higher in premature infants than in term infants. G6PD activity was higher in infants having low birth weight (&lt; 2500 g) than in ones having normal birth weight (≥ 2500 g). Only 45.54% of high-risk newborns were tested for diagonosis. Among them, 92.16% had diagnostic confirmation. G6PD deficiency in class II accounts for 31.91%, whereas class III accounts for 68.09%. Boys accounted for 87.23% and jaundice accounted for 82.98% of infants with G6PD deficiency. Only 6.38% of those had a family history of G6PDD deficiency. Conclusion: Da Nang Hospital for Women and Children’s newborn screening programme identified 1.12% of newborns as high risk for G6PD deficiency. Most neonates with G6PD deficiency were in classes II and III, with males being the main gender, and jaundice being the most common symptom. Key words: G6PD deficiency, newborn screening, hell blood, enzyme activity

Abstract WMP83: The Pentose Phosphate Pathway is Crucial for Combating Heme-Induced Ferroptosis in Red Blood Cells After ICH

Intracerebral hemorrhage (ICH) occurs upon blood vessel rupture, allowing blood into brain tissue. Red blood cells (RBCs) make up 99%+ of blood cells. Brain-trapped RBCs undergo phagocytosis; however, many RBCs lyse prior to being phagocytosed due to their abundance. RBC lysis releases hemoglobin and toxic heme, driving oxidative stress especially in lipid-rich plasma membranes (PM), causing tissue damage and ferroptosis. Few studies have explored RBC fate in ICH, but unraveling the factors governing RBC lysis may yield ICH therapies.In in vitro human and murine RBC cultures, we observed RBCs are exquisitely sensitive to heme-induced death with increased oxidized fatty acids (FAs), a ferroptosis marker (Fig 1A-B). The ferroptosis inducer Erastin validated RBC susceptibility to ferroptosis (Fig 1C). Heme-induced cell death was countered by β-mercaptoethanol (β-ME), N-acetylcysteine (NAC), ferrostatin-1 (Fer-1) and Vitamin E (Vit. E), ferroptosis inhibitors, confirming RBC death was due to ferroptosis (Fig 1D-G). Heme and Erastin induced RBC ferroptosis differs from eryptosis, RBC specific programmed cell death, as it isn't Ca++ dependent (Fig1H&amp;I). Unlike other cells, RBCs solely rely on the Pentose Phosphate Pathway (PPP) for NADPH production for oxidation defense. PPP inhibition with Dehydroisoandrosterone (DHEA) and treatment with ThioNa, an NADP+ synthesis inhibitor, both heightened heme-induced RBC ferroptosis (Fig 1J-L). These data support the PPP's role against heme-driven ferroptosis. Heme induced RBC ferroptosis may trigger a chain reaction of RBC lysis and ongoing heme release. Notably, 400 million people face G6PD deficiency, the rate-limiting PPP enzyme, leading to NADPH depletion in RBCs with enhanced susceptibility to oxidation. Hence, in addition to identifying the PPP in RBCs resistance to heme toxicity, our findings could aid in identifying a population that is particularly vulnerable to the devastating effects of ICH.

Are the New Kawasaki-like Syndromes in the Children Associated with COVID-19?

COVID-19 pandemic is severe acute respiratory syndrome is still ongoing since December in almost every countries and cities. This syndrome was first reported in December 2019 in Wuhan, China than first case was seen in Thailand and many COVID-19 cases are detected in all populations, and most of them recovered and age, comorbidities, gender, of COVID-19 deaths and the severity of the infection were changed according to the patients’ additional health risk parameters. Elderly population and people with chronic diseases have been categorized as major risk group, however some COVID-19 positive children have showed Kawasaki disease-like syndromes such as hyper-inflammatory state according to the current state same as adult patients infected by COVID-19. We suggested that glucose-6-phosphate dehydrogenase (G6PD) deficiency can make some children more vulnerable against COVID-19 infection same as adults, since this virus attacks hemoglobin and heme metabolism leading to the increased hemolysis and impaired oxygen transport to the tissues. G6PD deficiency is most affects males. Thus, possible correlation between COVID-19 infection and Kawasaki disease like syndromes in the especially male children should be further investigated and maybe children may be categorized as risk group in the future.

Basic new born and antenatal screening for aspirational districts: unique methods of management and treatment of inherited disorders

Background: Early screening, diagnosis and management program can contribute in reducing the burden of genetic disorders which can lead to early neonatal death or long-term disability in the vulnerable areas. UMMID (Unique Methods of Management and treatment of Inherited Disorders) and NIDAN (National Inherited Diseases Administration), aimed at developing a community level program for need assessment and to evaluate the feasibility of basic screening for some genetic/endocrine disorders in high-risk population. Methods: UMMID was carried out at the aspirational district Ranchi, Jharkhand for 3 years (2019-2022) to perform newborn screening (NBS) in &lt;7 days old newborn babies for 5 metabolic disorders and to screen antenatal mothers for prevention of thalassemia and other hemoglobinopathies. Results: G6PD deficiency being more prevalent in Ranchi district out of five metabolic disorders screened. 13.6% of screen positive cases were confirmed positive for hemoglobinopathies. c.20 A&gt;T is the most common mutation found among carriers. Conclusions: This initiative underscores the need of such screening programs in aspirational districts to manage and prevent these disorders effectively.

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.