Neutropenia congénita de tipo IV: reporte de un caso / Congenital neutropenia type IV: case report

La neutropenia congénita grave (NCG) es una entidad heterogénea cuya característica común es un recuento absoluto de neutrófilos inferior a 0,5 x 10 9/l. Presenta gran heterogeneidad genética, las mutaciones más frecuentes son las del gen de la elastasa 2 (ELA 2). El tratamiento de primera elección es la administración de factor estimulador de colonias de granulocitos. Los pacientes con NCG presentan infecciones graves en etapas tempranas de la vida. Se presenta una paciente con NCG asociada a fenotipo peculiar con facies triangular, retromicrognatia, patrón venoso prominente en miembros inferiores, comunicación interauricular y mal progreso ponderal, en quien se diagnosticó déficit de la enzima glucosa 6 fosfato deshidrogenasa, subunidad catalítica 3 (G6PC3). A pesar de lo infrecuente de esta mutación como causa de NCG (2 %), su conocimiento cobra importancia porque la coexistencia del fenotipo característico con una NCG orienta en la solicitud del estudio genético que permite arribar al diagnóstico.

Severe congenital neutropenia (SCN) is a heterogeneous disease whose more common feature is an absolute neutrophil count less than 0.5 x 10 9/l. It presents great genetic heterogeneity. Autosomal dominant inherited mutations of the elastase 2 gene (ELA2) represent the most common etiology. The first choice treatment is the administration of granulocyte colony stimulating factor. Patients with SCN develop severe infections early in life. We present a patient who associated SCN to a peculiar phenotype, characterized by triangular facies, retromicrognathia, prominent venous pattern in the lower limbs, atrial septal defect and poor weight progress, in whom a deficiency of the enzyme glucose 6 phosphate dehydrogenase, a catalytic subunit 3 (G6PC3), was diagnosed. Despite the infrequency of this mutation as the origin of SCN (2%), its knowledge becomes important because the coexistence of the characteristic phenotype and SCN guides the request for the genetic study that allows reaching the diagnosis.

Bridging the gap in the recall of G6PD deficient screened babies: A policy brief

@#Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency is an enzyme defect affecting around 400 million people worldwide. In the Philippines, cumulative data from the Newborn Screening Reference Center as of December 2020 unveils 248,285 confirmed babies out of 15,087,251 screened babies or prevalence rate of 1:60 with the national return rate of 18% only (NSRC, 2021). One strategy identified pertaining to the recall of patient is the G6PD Recall Monitoring which resulted in a 76% G6PD return rate, compared to the 31% output of the standard recall done in the Province of Ilocos Norte in CY 2020 (NSC-NL, 2022). Hence, this policy brief on G6PD Recall Monitoring serves as a supplementary policy to bridge the gaps in the recall of G6PD Deficient Patients and increase return rate of G6PD nationwide.

Genetic Mutation Characteristics of Glucose-6-Phosphate Dehydrogenase Deficiency Patients in Wuhan / 中国实验血液学杂志

OBJECTIVE@#To explore the genotype mutation characteristics of patients with glucose-6-phosphate dehydrogenase(G6PD) deficiency in Wuhan.@*METHODS@#A total of 1 321 neonates with positive screening and outpatients were received G6PD mutation detection, 12 kinds of common G6PD mutation in Chinese people was detected by using multicolor melting curve analysis (MMCA) method, for those with negative results, the enzyme activity and clinical information were analyzed, sequencing was recommended after informed consent when it is necessary.@*RESULTS@#Among 1321 patients, a total of 768 mutations were detected out, with a detection rate of 58.1%. A total of 18 types of G6PD genotypes were identified, including c.1388G>A, c.1376G>T, c.95G>A, c.1024C>T, c.871G>A, c.392G>T, c.487G>A, c.1360C>T, c.1004C>A, c.517T>C, c.592C>T, c.94C>G, c.152C>T, c.320A>G, c.1028A>G, c.1316G>A, c.1327G>C and c.1376G>C, including 683 male hemizygotes, 3 female homozygotes, 80 female heterozygotes and 2 female compound heterozygous.@*CONCLUSION@#A total of 18 types of G6PD mutations are identified in the reaserch, and c.94C>G, c.1028A>G and c.1327G>C are first reported in Chinese population. The most common G6PD mutation types in Wuhan are c.1388G>A, c.1376G>T, c.95G>A.

Circadian effects of ionizing radiation on reproductive function and clock genes expression in male mouse

BACKGROUND@#Exposure to the ionizing radiation (IR) encountered outside the magnetic field of the Earth poses a persistent threat to the reproductive functions of astronauts. The potential effects of space IR on the circadian rhythms of male reproductive functions have not been well characterized so far.@*METHODS@#Here, we investigated the circadian effects of IR exposure (3 Gy X-rays) on reproductive functional markers in mouse testicular tissue and epididymis at regular intervals over a 24-h day. For each animal, epididymis was tested for sperm motility, and the testis tissue was used for daily sperm production (DSP), testosterone levels, and activities of testicular enzymes (glucose-6-phosphate dehydrogenase (G6PDH), sorbitol dehydrogenase (SDH), lactic dehydrogenase (LDH), and acid phosphatase (ACP)), and the clock genes mRNA expression such as Clock, Bmal1, Ror-α, Ror-β, or Ror-γ.@*RESULTS@#Mice exposed to IR exhibited a disruption in circadian rhythms of reproductive markers, as indicated by decreased sperm motility, increased daily sperm production (DSP), and reduced activities of testis enzymes such as G6PDH, SDH, LDH, and ACP. Moreover, IR exposure also decreased mRNA expression of five clock genes (Clock, Bmal1, Ror-α, Ror-β, or Ror-γ) in testis, with alteration in the rhythm parameters.@*CONCLUSION@#These findings suggested potential health effects of IR exposure on reproductive functions of male astronauts, in terms of both the daily overall level as well as the circadian rhythmicity.

Screening results and genetic features of glucose-6-phosphate dehydrogenase deficiency in 54 025 preterm infants in Chengdu, China / 中国当代儿科杂志

OBJECTIVE@#To analyze the screening results of glucose-6-phosphate dehydrogenase (G6PD) deficiency and gene mutation distribution of G6PD deficiency in preterm infants in Chengdu, China, in order to provide a basis for the improvement of G6PD screening process in preterm infants.@*METHODS@#Fluorescent spot test for G6PD deficiency using dried blood spots was used for G6PD screening of 54 025 preterm infants born from January 1, 2015 to December 31, 2019 in Chengdu, and G6PD enzymology and gene detection were used for the diagnosis of 213 infants with positive screening results.@*RESULTS@#Among the 54 025 preterm infants, 192 were diagnosed with G6PD deficiency, with an incidence rate of 3.55‰. The incidence rate of G6PD deficiency in preterm infants was higher than that in full-term infants in the same period of time and tended to increase year by year. Birth in summer, gestational age T mutation tend to have mild conditions.

Gene Mutants and Their Clinical Characteristics of G6PD Deficiency Among Children in Luzhou Area / 中国实验血液学杂志

OBJECTIVE@#To study the gene mutants of G6PD deficiency and their clinical featuers among children in Luzhou area.@*METHODS@#732 children with suspected G6PD deficiency in Luzhou area from March 2017 to July 2019 were selected, which were examined for G6PD enzyme activity and gene mutation. The G6PD enzyme activity was detected by ultraviolet rate quantification, and the gene mutation was detected by melting curve analysis-based PCR assay, and the clinical characteristics of different mutants when acute hemolysis happens were analyzed.@*RESULTS@#387 positive specimens were detected in 732 specimens, among which the gene mutation and the enzyme activity decrease was found in specimens 326, 49 specimens showed gene mutation but without the enzyme activity decrease, and 12 specimens without gene mutation but with the enzyme activity decrease. Among 375 positive samples with gene mutation, c.1376G＞T, c.1388G＞A, c.1024C＞T and c.95A＞G were the most common. The enzyme activity of c.1376G＞T and c.1388G＞A was statistically significantly different with c.1024C＞T. The most common incentives of acute hemolysis was broad bean, the reticulocyte count was statistically significantly different among c.1376G＞T, c.1388G＞A and c.95A＞G. The hemoglobin level of c.1376G＞T was statistically significantly different from with c.95A＞G. Moreover, c.1376G＞T, c.1388G＞A was lower than c.1024 C＞T. When acute hemolysis occurs, the reticulocyte count and hemoglobin changes were different between different mutation types, while the patients age, hospitalization time, blood transfusion, total bilirubin, and urine color recovery time of the patients were not statistically different.@*CONCLUSION@#The common mutants of G6PD deficiency among children in Luzhou area are c.1376G＞T, and c.1388G＞A, c.1024C＞T. Favism is the most common clinical manifestation of G6PD deficiency.

Recent trends of glucose-6-phosphate dehydrogenase deficiency among saudi population in Riyadh city / Tendências recentes da deficiência de glicose-6-fosfato desidrogenase entre a população saudita na cidade de Riade

G6PD deficiency is associated with erythrocyte deficiency in the X-chromosome enzyme. It causes a hematologic syndrome called hemolytic anemia that connects G6PD deficiency with X-linked condition. In the Middle East, including Saudi Arabia, G6PD deficiency is the most dominant genetic blood disorders. It results in higher rates of mortality and morbidity due to its incurable long-lasting nature and prevalence of physical and psychological incapacities. In this study, an attempt was made to evaluate the prevalence of G6PD deficiency among the Saudi population in Riyadh city. A cross-sectional retrospective study was conducted at King Saud University Medical City in Riyadh, Saudi Arabia. The population of the study comprised randomly chosen males and females who visited the hospital from January 2017 to January 2018. Statistical analyses were performed using SPSS, and descriptive analysis was used to find the frequency of G6PD-deficient patients. Out of the 209 patients, 62.2% were males (n=130) and 37.8% were females (n=79). Twenty males and 6 females were found to have G6PD deficiency, with the male to female ratio being 1:3. Out of the total 130 male participants, 20 patients were found to be enzyme deficient and 6 patients of 79 female patients were found to be G6PD deficient. There were 38.4% (n=10) patients with G6PD level <4 units/gram hemoglobin, 26.9% (n=7) patients had G6PD levels of 4.1­7.0 units/gram hemoglobin, and 34.6% (n=9) patients had >7 units/gram hemoglobin. Among the G6PD patients, 23.07% patients were severely anemic, and 5 (19.2%) patients were reported to have high bilirubin. The present study revealed the G6PD prevalence to be 12.4% among the Saudi population; this value is significantly higher than that found in France, Spain, India, and Singapore. In the Saudi population, males are more vulnerable to G6PD-deficient than females. Hence, attention should be paid to G6PD-deficient patients while prescribing antimalarial medication. Such patients may be advised to avoid certain foods to minimize the risk of having hemolytic episodes.

A deficiência de G6PD está associada à deficiência de eritrócitos na enzima do cromossomo X. Causa uma síndrome hematológica chamada anemia hemolítica que conecta a deficiência de G6PD à condição ligada ao X. No Oriente Médio, incluindo a Arábia Saudita, a deficiência de G6PD é o distúrbio genético do sangue mais dominante. Isso resulta em maiores taxas de mortalidade e morbidade devido à sua natureza incurável e duradoura e à prevalência de incapacidades físicas e psicológicas. Neste estudo, foi feita uma tentativa de avaliar a prevalência de deficiência de G6PD entre a população saudita na cidade de Riade. Um estudo retrospectivo transversal foi realizado na cidade médica da Universidade King Saud, em Riade, na Arábia Saudita. A população do estudo compreendeu homens e mulheres escolhidos aleatoriamente que visitaram o hospital entre janeiro de 2017 e janeiro de 2018. As análises estatísticas foram realizadas com o SPSS e a análise descritiva foi utilizada para determinar a frequência de pacientes com deficiência de G6PD. Dos 209 pacientes, 62,2% eram do sexo masculino (n = 130) e 37,8% eram do sexo feminino (n = 79). Verificou-se que 20 homens e 6 mulheres apresentavam deficiência de G6PD, sendo a proporção homem/mulher de 1:3. Do total de 130 participantes do sexo masculino, 20 pacientes apresentaram deficiência de enzima e 6 de 79 pacientes do sexo feminino apresentaram deficiência de G6PD. Havia 38,4% (n = 10) pacientes com nível de G6PD < 4 unidades/grama de hemoglobina, 26,9% (n = 7) pacientes tinham níveis de G6PD de 4,1-7,0 unidades/grama de hemoglobina e 34,6% (n = 9) pacientes tinham > 7 unidades/grama de hemoglobina. Entre os pacientes com G6PD, 23,07% eram severamente anêmicos e cinco (19,2%) pacientes relataram ter alta bilirrubina. O presente estudo revelou que a prevalência de G6PD é de 12,4% na população saudita; esse valor é significativamente maior que o encontrado na França, Espanha, Índia e Cingapura. Na população saudita, os homens são mais vulneráveis à deficiência de G6PD do que as mulheres. Portanto, deve-se prestar atenção aos pacientes com deficiência de G6PD durante a prescrição de medicamentos antimaláricos. Esses pacientes podem ser aconselhados a evitar certos alimentos para minimizar o risco de episódios hemolíticos.

Betaine supplementation improved L-threonine fermentation of Escherichia coli THRD by upregulating zwf (glucose-6-phosphate dehydrogenase) expression

BACKGROUND: The supplementation of betaine, an osmoprotective compatible solute, in the cultivation media has been widely used to protect bacterial cells. To explore the effects of betaine addition on industrial fermentation, Escherichia coli THRD, an L-threonine producer, was used to examine the production of L-threonine with betaine supplementation and the underlying mechanism through which betaine functions was investigated. RESULTS: Betaine supplementation in the medium of E. coli THRD significantly improved L-threonine fermentation parameters. The transcription of zwf and corresponding enzyme activity of glucose-6-phosphate dehydrogenase were significantly promoted by betaine addition, which contributed to an enhanced expression of zwf that provided more nicotinamide adenine dinucleotide phosphate (NADPH) for L-threonine synthesis. In addition, as a result of the betaine addition, the betaine-stimulated expression of enhanced green fluorescent protein (eGFP) under the zwf promoter within a plasmid-based cassette proved to be a transcription-level response of zwf. Finally, the promoter of the phosphoenolpyruvate carboxylase gene ppc in THRD was replaced with that of zwf, while L-threonine fermentation of the new strain was promoted by betaine addition. Conclusions: We reveal a novel mode of betaine that facilitates the microbial production of useful compounds. Betaine supplementation upregulates the expression of zwf and increases the NADPH synthesis, which may be beneficial for the cell growth and thereby promote the production of L-threonine. This finding might be useful for the production of NADPH-dependent amino acids and derivatives in E. coli THRD or other E. coli strains.

The Pentose Phosphate Pathway as a Potential Target for Cancer Therapy

During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation. Thus, metabolic reprogramming of NADPH homeostasis is an important step in cancer progression as well as in combinational therapeutic approaches. In mammalian, the pentose phosphate pathway (PPP) and one-carbon metabolism are major sources of NADPH production. In this review, we focus on the importance of glucose flux control towards PPP regulated by oncogenic pathways and the potential therein for metabolic targeting as a cancer therapy. We also summarize the role of Snail (Snai1), an important regulator of the epithelial mesenchymal transition (EMT), in controlling glucose flux towards PPP and thus potentiating cancer cell survival under oxidative and metabolic stress.

The effects of Brassica juncea L. leaf extract on obesity and lipid profiles of rats fed a high-fat/high-cholesterol diet

BACKGROUND/OBJECTIVES: Obesity is a global health problem of significant importance which increases mortality. In place of anti-obesity drugs, natural products are being developed as alternative therapeutic materials. In this study, we investigated the effect of Brassica juncea L. leaf extract (BLE) on fat deposition and lipid profiles in high-fat, high-cholesterol diet (HFC)-induced obese rats. MATERIALS/METHODS: Male Sprague-Dawley rats were divided into four groups (n = 8 per group) according to diet: normal diet group (ND), high-fat/high-cholesterol diet group (HFC), HFC with 3% BLE diet group (HFC-A1), and HFC with 5% BLE diet group (HFC-A2). Each group was fed for 6 weeks. Rat body and adipose tissue weights, serum biochemical parameters, and tissue lipid contents were determined. The expression levels of mRNA and proteins involved in lipid and cholesterol metabolism were determined by reverse transcription polymerase chain reaction and western blot analysis, respectively. RESULTS: The HFC-A2 group showed significantly lower body weight gain and food efficiency ratio than the HFC group. BLE supplementation caused mesenteric, epididymal, and total adipose tissue weights to decrease. The serum levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced, and high-density lipoprotein cholesterol was significantly increased in rats fed BLE. These results were related to lower glucose-6-phosphate dehydrogenase, acetyl-coA carboxylase, and fatty acid synthase mRNA expression, and to higher expression of the cholesterol 7α-hydroxylase and low density lipoprotein-receptor, as well as increased protein levels of peroxisome proliferator-activated receptor α. Histological analysis of the liver revealed decreased lipid droplets in HFC rats treated with BLE. CONCLUSIONS: Supplementation of HFC with 3% or 5% BLE inhibited body fat accumulation, improved lipid profiles, and modulated lipogenesis- and cholesterol metabolism-related gene and protein expression.

mRNA Expression of SLC5A5 and SLC2A Family Genes in Papillary Thyroid Cancer: An Analysis of The Cancer Genome Atlas

PURPOSE: The present study investigated the dynamics and prognostic role of messenger RNA (mRNA) expression responsible for 18F-fluorodeoxyglucose (FDG) uptake in FDG positron emission tomography (PET) and radioactive iodine (131I) uptake in whole-body radioactive iodine scans (WBS) in papillary thyroid cancer (PTC) patients. MATERIALS AND METHODS: The primary and processed data were downloaded from the Genomic Data Commons Data Portal. Expression data for sodium/iodide symporter (solute carrier family 5 member 5, SLC5A5), hexokinase (HK1–3), glucose-6-phosphate dehydrogenase (G6PD), and glucose transporter (solute carrier family 2, SLC2A1–4) mRNA were collected. RESULTS: Expression of SLC5A5 mRNA were negatively correlated with SLC2A1 mRNA and positively correlated with SLC2A4 mRNA. In PTC with BRAF mutations, expressions of SLC2A1, SLC2A3, HK2, and HK3 mRNA were higher than those in PTC without BRAF mutations. Expression of SLC5A5, SLC2A4, HK1, and G6PD mRNA was lower in PTC without BRAF mutation. PTCs with higher expression of SLC5A5 mRNA had more favorable disease-free survival, but no association with overall survival. CONCLUSION: Expression of SLC5A5 mRNA was negatively correlated with SLC2A1 mRNA. This finding provides a molecular basis for the management of PTC with negative WBS using 18F-FDG PET scans. In addition, higher expression of SLC5A5 mRNA was associated with less PTC recurrence, but not with deaths.

Global gene expression analysis in liver of db/db mice treated with catalpol / 中国天然药物

Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.

Genetic mutation screening of glucose-6-phosphate dehydrogenase deficiency in Dongguan district / 中华医学遗传学杂志

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

Global gene expression analysis in liver of db/db mice treated with catalpol / 中国天然药物

Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.

Change of G6PD Activity in Children with Acute Leukemia and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To explore the change of G6PD activity in children with acute leukemia（AL）and its correlation with the clinical characteristics.@*METHODS@#The G6PD activity in peripheral blood samples from 74 children disagnosed as AL (50 cases of ALL, and 24 cases of AML) was detected by Zinkham method recommended by WHO in 1967, and its relevance with clinical indicators was statistically analyzed. The peripheral blood samples of 70 healthy children were used as the controls.@*RESULTS@#The G6PD activity in ALL and AML groups was significantly lower than that in the control group (P=0.000, P=0.000) and there was no statistical difference between ALL and AML groups. The G6PD activity in bacterial, fungal infection and non-infection groups (no bacterial and fungal infection) were statistically different from control group (P=0.02, P=0.001, P=0.001), respectively. The G6PD activity in bacterial infection group and non-infection group was statistically different from with fungal infection group (P=0.004, P=0.019), respectively. The G6PD activity linearly correlated with leukocyte count and neutrophil percentage in AL children (P=0.000, P=0.001, r=0.465, r=0.434), respectively. The median survival time of G6PD activity deficiency group was higher than that in the normal group, but without statistically significant difference (P=0.4149).@*CONCLUSION@#The G6PD activity in AL children is significantly lower than that in healthy children, and the G6PD activity linearly relates with leukocyte count and neutrophil percentage of AL children. The patients with G6PD activity deficiency is more susceptible to fungal infection, moreover the infection is more serious.

Expression of gene in wild type zebrafish embryos of early development / 浙江大学学报·医学版

OBJECTIVE@#: To observe the expression of gene in the early development stage of wild zebrafish embryos.@*METHODS@#: The collinearity of gene and the sequence similarity of G6pd protein were analyzed with gene database and BLAST software, respectively. Expression of gene in different development stages of zebrafish embryos was detected by hybridization. The -EGFP-pCS recombinant plasmids were microinjected into zebrafish embryos, and fluorescence was observed under a fluorescence microscope. The expression of G6pd protein at 24, 48 and 72 hour post fertilization (hpf) zebrafish embryos was detected by Western blotting; the enzyme activity of G6pd at 24, 48 and 72 hpf zebrafish embryos was detected by modified G6pd quantitative ratio method.@*RESULTS@#: The G6pd protein similarity of zebrafish and human was 88%, and that of zebrafish and mouse was 87%. The results of hybridization showed that the gene was mainly expressed in the hematopoietic tissues of zebrafish; the results observed after microinjection of -EGFP-pCS recombinant plasmid were consistent with the results of hybridization. At 24, 48 and 72 hpf, the relative expression levels of G6pd protein in zebrafish embryos were 1.44±0.03, 1.47±0.05, and 1.54±0.02, respectively(>0.05); the G6pd enzyme activity levels were 1.74±0.17, 1.75±0.12, 1.71±0.22, respectively (>0.05).@*CONCLUSIONS@#: The study has observed the expression of gene and G6pd protein, and G6pd enzyme activity in zebrafish embryos at different development phases, which provides a reference for the establishment of a zebrafish G6PD deficiency model.

Neonatal indirect hyperbilirubinemia and glucose-6-phosphate dehydrogenase deficiency / 소아과

PURPOSE: This study aimed to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among infants with neonatal indirect hyperbilirubinemia (NIH); compare G6PD-deficient and G6PD-normal patients regarding hyperbilirubinemia and need for exchange transfusions (ET); and assess risk factors for ET and kernicterus. METHODS: This is a case-control retrospective study. Medical records of NIH patients admitted to the Pediatric Department, Salmaniya Medical Complex, Bahrain, between January 2007 and June 2010 were reviewed. Data on sex, age at presentation, hospitalization duration, need for ET, hemoglobin (Hb) level, reticulocyte count, direct Coombs test, serum total and indirect bilirubin levels, thyroid function, blood and urine cultures, G6PD status, and blood groups were collected and compared between the G6PD-deficent and G6PD-normal patients. RESULTS: Of 1,159 NIH patients admitted, 1,129 were included, of whom 646 (57%) were male. Among 1,046 patients tested, 442 (42%) were G6PD deficient, 49 (4%) needed ET, and 11 (1%) had suspected Kernicterus. The G6PD-deficient patients were mainly male (P<0.0001), and had lower Hb levels (P<0.0001) and higher maximum bilirubin levels (P=0.001). More G6PD-deficient patients needed ET (P<0.0001). G6PD deficiency (P=0.006), lower Hb level (P=0.002), lower hematocrit count (P=0.02), higher bilirubin level (P<0.0001), higher maximal bilirubin level (P<0.0001), and positive blood culture result (P<0.0001) were significant risk factors for ET. Maximal bilirubin level was a significant risk factor for kernicterus (P=0.021) and independently related to ET (P=0.03). CONCLUSION: G6PD deficiency is an important risk factor for severe NIH. In G6PD-deficent neonates, management of NIH should be hastened to avoid irreversible neurological complications.

Anesthetic management of a patient with glucose-6-phosphate dehydrogenase deficiency undergoing robot-assisted laparoscopic surgery: A case report

The authors describe the successful perioperative management of a 3-year-old boy from Dubai with glucose-6-phosphate dehydrogenase (G6PD) deficiency, who underwent robot-assisted laparoscopic pyeloplasty for complete right ureteropelvic junction obstruction. G6PD deficiency is a genetic disorder predisposing patients to hemolytic anemia from oxidative stress. Important considerations in anesthetic management include avoiding oxidative stress, which can be caused by various conditions, and monitoring for hypercapnia, which can cause acidosis and hemolysis. Laparoscopic surgery is usually associated with hypercapnia and therefore an increased risk for respiratory acidosis. During surgery in this particular case, efforts were made to avoid carbon dioxide retention and to keep the patient warm. General anesthesia was induced with thiopental sodium, rocuronium, and fentanyl, and maintained with sevoflurane. There were no signs of hemolysis in the perioperative period and he was discharged owing to his improved condition.

Genetic Profiles of Korean Patients With Glucose-6-Phosphate Dehydrogenase Deficiency

BACKGROUND: We describe the genetic profiles of Korean patients with glucose-6-phosphate dehydrogenase (G6PD) deficiencies and the effects of G6PD mutations on protein stability and enzyme activity on the basis of in silico analysis. METHODS: In parallel with a genetic analysis, the pathogenicity of G6PD mutations detected in Korean patients was predicted in silico. The simulated effects of G6PD mutations were compared to the WHO classes based on G6PD enzyme activity. Four previously reported mutations and three newly diagnosed patients with missense mutations were estimated. RESULTS: One novel mutation (p.Cys385Gly, labeled G6PD Kangnam) and two known mutations [p.Ile220Met (G6PD São Paulo) and p.Glu416Lys (G6PD Tokyo)] were identified in this study. G6PD mutations identified in Koreans were also found in Brazil (G6PD São Paulo), Poland (G6PD Seoul), United States of America (G6PD Riley), Mexico (G6PD Guadalajara), and Japan (G6PD Tokyo). Several mutations occurred at the same nucleotide, but resulted in different amino acid residue changes in different ethnic populations (p.Ile380 variant, G6PD Calvo Mackenna; p.Cys385 variants, Tomah, Madrid, Lynwood; p.Arg387 variant, Beverly Hills; p.Pro396 variant, Bari; and p.Pro396Ala in India). On the basis of the in silico analysis, Class I or II mutations were predicted to be highly deleterious, and the effects of one Class IV mutation were equivocal. CONCLUSIONS: The genetic profiles of Korean individuals with G6PD mutations indicated that the same mutations may have arisen by independent mutational events, and were not derived from shared ancestral mutations. The in silico analysis provided insight into the role of G6PD mutations in enzyme function and stability.

Mass spectrometry based proteomics profiling of human monocytes

Human monocyte is an important cell type which is involved in various complex human diseases. To better understand the biology of human monocytes and facilitate further studies, we developed the first comprehensive proteome knowledge base specifically for human monocytes by integrating both in vivo and in vitro datasets. The top 2000 expressed genes from in vitro datasets and 779 genes from in vivo experiments were integrated into this study. Altogether, a total of 2237 unique monocyte-expressed genes were cataloged. Biological functions of these monocyte-expressed genes were annotated and classified via Gene Ontology (GO) analysis. Furthermore, by extracting the overlapped genes from in vivo and in vitro datasets, a core gene list including 541 unique genes was generated. Based on the core gene list, further gene-disease associations, pathway and network analyses were performed. Data analyses based on multiple bioinformatics tools produced a large body of biologically meaningful information, and revealed a number of genes such as SAMHD1, G6PD, GPD2 and ENO1, which have been reported to be related to immune response, blood biology, bone remodeling, and cancer respectively. As a unique resource, this study can serve as a reference map for future in-depth research on monocytes biology and monocyte-involved human diseases.