Manejo anestésico del déficit de glucosa 6-fosfato deshidrogenasa / Anesthetic management of glucose 6-phosphate dehydrogenase deficiency

El déficit de glucosa 6-fosfato deshidrogenasa es la enzimopatía más frecuente de los glóbulos rojos, contando con una prevalencia de 400 millones de personas en el mundo y una herencia ligada al cromosoma X, afectando sobre todo a varones. La glucosa 6-fosfato-deshidrogenasa participa en la vía de las pentosas-fosfato, encargada del metabolismo celular, y produciendo antioxidantes. Un déficit de esta enzima altera su capacidad de proteger a los hematíes del estrés oxidativo que producen ciertos medicamentos, condiciones metabólicas, infecciones y alimentos. Se requieren consideraciones anestésicas específicas para disminuir la morbimortalidad asociada a intervenciones médico-quirúrgicas en pacientes con esta enfermedad. En este artículo se expone el caso de un varón de 45 años con este déficit enzimático sometido a anestesia general combinada para resección anterior baja de recto programada.(AU)

Glucose 6-phosphate dehydrogenase deficiency is the most common enzyme disease of red blood cells, with around 400 million people suffering from it throughout the world and linked to the X chromosome inheritance, thus it predominantly affects men. Glucose 6-phosphate-dehydrogenase participates in the pentose-phosphate pathway, being responsible for cellular metabolism and the production of antioxidants. A deficiency of this enzyme alters its ability to protect red blood cells from oxidative stress caused by certain drugs, metabolic conditions, infections and food. Specific anesthetic considerations are required to reduce the morbidity and mortality associated with medical-surgical interventions in patients with this disease. This article presents the case of a 45-year-old man with Glucose 6-Phosphate Dehydrogenase deficiency who underwent combined general anesthesia for programmed low anterior resection of the rectum.(AU)

Favism: Clinical Features at Different Ages.

Favism is a hemolytic disease due to the ingestion of fava beans in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. There is wide inter- and intra-individual variability in the development of hemolytic crisis, and several factors influence it: quantity, quality, ripeness of fava beans, and age of onset. In this narrative review of case reports and case series, we reported the predisposing factors and clinical features for four different age groups classified as follows: pregnant women and infants (i.e., exclusively breastfed children); children, from weaned to 11 years; preadolescents and adolescents, from 11 to 18 years; and adults (18 years and older). Some symptoms developed only in specific age groups: death in infants; visual impairment in children; systolic murmur in infants, children, and adolescents; and renal failure in adults. In youngest children or pregnant women the severity is the highest. Some other symptoms were present in all: jaundice, increased bilirubin, splenomegaly, hepatomegaly, discolored urine, tachycardia, pallor, abdominal pain, malaise, vomit, nausea, and dizziness. Laboratory findings are characterized by anemia, reticulocytosis, elevated bilirubin level, and sometimes urinary urobilinogen and methemoglobinemia. In most cases the symptomatology is self-limited and does not release sequelae, but hospitalization and transfusion are often required.

Déficit de glucosa-6-fosfato deshidrogenasa asociado a rasgo falciforme: importancia de una buena historia clínica / Glucose-6-phosphate dehydrogenase deficiency associated with sickle cell trait: importance of a good medical history

Introducción: El déficit de glucosa-6-fosfato deshidrogenasa es la alteración enzimática más frecuente a nivel eritrocitario. El debut característico lo constituye un paciente previamente sano en el que se desencadena una crisis hemolítica por determinados fármacos, infecciones o alimentos. En este último contexto es conocido como favismo el cuadro clínico secundario a la ingesta de habas. Caso clínico. Varón de 23 meses que consulta por fiebre, ictericia, palidez y coluria. Como antecedente personal de interés destaca la determinación de un rasgo falciforme en el cribado neonatal. Los resultados de la analítica sanguínea son compatibles con una crisis hemolítica no inmune, por lo que se establece como hipótesis diagnóstica una anemia hemolítica desencadenada por proceso infeccioso en paciente con rasgo falciforme. Puesto que el rasgo falciforme es asintomático, durante el ingreso se amplíó la anamnesis detectándose al menos un episodio de similares características, pero más leve, y al incidir en la dieta familiar se confirmó la ingesta intermitente de habas. Ante la posibilidad de favismo se solicitó análisis genético que confirmó el diagnóstico. Conclusiones. Las complicaciones de las enfermedades de base de cada paciente frecuentemente causan sus patologías, pero no siempre es así. Es fundamental realizar una anamnesis exhaustiva, dado que esta puede ofrecer claves diagnósticas inesperadas.(AU)

Introduction. Glucose-6-phosphate dehydrogenase deficiency is the most common enzymatic alteration at the erythrocyte level. The characteristic onset is a previously healthy patient in whom a hemolytic crisis is triggered by certain drugs, infections or foods. In this latter context, the clinical condition secondary to the ingestion of broad beans is known as favism. Clinical case. A 23-month-old male presented with fever, jaundice and choluria. As a personal history of interest, the determination of a sickle cell trait in neonatal screening stands out. The blood test results are compatible with a non-immune hemolytic crisis, so the diagnostic hypothesis is established as a hemolytic anemia triggered by an infectious process in a patient with sickle cell trait. During their stay in the ward, the anamnesis is expanded, detecting at least one episode with similar but milder characteristics and by influencing the family diet, the intermittent intake of beans at least once a month is confirmed. Given the possibility of favism, genetic analysis is requested to confirm the diagnosis. Conclusions. The complications of each patient’s underlying diseases often cause their pathologies, but this is not always the case. It is essential to carry out an exhaustive anamnesis, since this can offer unexpected.(AU)

A Simple High-Throughput Method for the Analysis of Vicine and Convicine in Faba Bean.

The faba bean is one of the earliest domesticated crops, with both economic and environmental benefits. Like most legumes, faba beans are high in protein, and can be used to contribute to a balanced diet, or as a meat substitute. However, they also produce the anti-nutritional compounds, vicine and convicine (v-c), that when enzymatically degraded into reactive aglycones can potentially lead to hemolytic anemia or favism. Current methods of analysis use LC-UV, but are only suitable at high concentrations, and thus lack the selectivity and sensitivity to accurately quantitate the low-v-c genotypes currently being developed. We have developed and fully validated a rapid high-throughput LC-MS method for the analysis of v-c in faba beans by optimizing the extraction protocol and assessing the method of linearity, limit of detection, limit of quantitation, accuracy, precision and matrix effects. This method uses 10-times less starting material; removes the use of buffers, acids and organic chemicals; and improves precision and accuracy when compared to current methods.

Almond oil restores blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology more efficiently than olive oil in favism.

OBJECTIVES: Favism is a metabolic disease and this study aimed to compare between olive oil and almond oil to ameliorate blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology in favism rats. METHODS: Animals were 36 male albino rats. They classified to 2 equal (normal and favism) groups. Normal group classified to 3 equal subgroups; Control, Olive oil, and Almond oil subgroups: normal rats orally administrated with 1 mL/100 g of saline, olive oil, and almond oil, respectively. Favism group was subdivided into 3 equal subgroup; favism, favism + olive oil, and favism + almond oil subgroups: favism rats orally administrated with no treatment, 1 mL/100 g olive oil, and 1 mL/100 g almond oil, respectively. All treatments were administrated orally by oral gavage once a day for 1 month. RESULTS: The hemoglobin, hematocrite, the blood cells, glucose and glucose-6-phosphate dehydrogenase, aspartate and alanine aminotransferase, total proteins, albumin, and globulin in serum were decreased in favism. The glutathione, superoxide dismutase, and glutathione peroxidase in blood and liver were decreased in favism while alkaline phosphatase and total bilirubin in serum were increased in favism. The blood and liver malondialdehyde was increased in favism. Furthermore, oral administration with both oils in favism rats restored all these parameters to be approached the control levels. Also, both oils preserved blood and liver DNA and liver histology. CONCLUSIONS: Almond oil restored blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology more efficiently than olive oil in favism.

Surprising Structural and Functional Properties of Favism Erythrocytes Are Linked to Special Metabolic Regulation: A Cell Aging Study.

Favism uniquely arises from a genetic defect of the Glucose-6 Phosphate Dehydrogenase (G6PD) enzyme and results in a severe reduction of erythrocytes' (RBCs) reducing power that impairs the cells' ability to respond to oxidative stresses. After exposure to fava beans or a few other drugs, the patients experience acute hemolytic anemia due to RBCs' lysis both intra and extra-vascularly. In the present paper, we compared selected biochemical, biophysical, and ultra-morphological properties of normal RBCs and cells from favism patients measured along cellular aging. Along the aging path, the cells' characteristics change, and their structural and functional properties degrade for both samples, but with different patterns and effectors that have been characterized in biophysical and biochemical terms. In particular, the analysis revealed distinct metabolic regulation in G6DP-deficient cells that determines important peculiarities in the cell properties during aging. Remarkably, the initial higher fragility and occurrence of structural/morphological alterations of favism cells develop, with longer aging times, into a stronger resistance to external stresses and higher general resilience. This surprisingly higher endurance against cell aging has been related to a special mechanism of metabolic regulation that permits lower energy consumption in environmental stress conditions. Our results provided a direct and coherent link between the RBCs' metabolic regulation and the cell properties that would not have been possible to establish without an investigation performed during aging. The consequences of this new knowledge, in particular, can be discussed in a more general context, such as understanding the role of the present findings in determining the characteristics of the favism pathology as a whole.

Metabolic profiling reveals alterations in the erythrocyte response to fava bean ingestion in G6PD-deficient mice.

BACKGROUND: Favism is an acute hemolytic syndrome caused by fava bean (FB) ingestion. The purpose of this study was to investigate the possible influences of FB on the metabonomic profile of erythrocytes in glucose-6-phosphate dehydrogenase (G6PD)-deficient (G6PDx) and wild-type (WT) mice. RESULTS: Ninety-two metabolites were identified in the comparison of the G6PDx and WT groups. Eighty-seven metabolites were identified in the erythrocytes of WT and G6PDx mice after FB ingestion. Thirty-eight metabolites were identified in the comparison of the FB-treated G6PDx and the FB-treated WT mouse groups. Among them, the number of glycerophospholipids (GPLs) and polyunsaturated fatty acids (PUFAs) changed significantly, which suggests that GPLs and PUFAs may be responsible for FB stress. CONCLUSION: This study demonstrates that G6PD deficiency might affect the metabonomic profile of erythrocytes in response to FB. © 2020 Society of Chemical Industry.

Clinical Manifestations and Therapeutic Findings of the Children with Glucose-6-Phosphate Dehydrogenase Deficiency Presenting Favism.

AIM: Favism is characterized as acute anemia, due to Glucose-6-phosphate dehydrogenase (G6PD) deficiency as a result of fava beans intake. It is associated with paleness, jaundice, and hemoglobinuria. In this study, signs, symptoms and therapeutic findings of the patients with hemolysis due to G6PD deficiency were investigated in Shahid Madani Hospital of Khorramabad, Lorestan. METHODS: This is a single-center cross-sectional descriptive study that was conducted on all children with G6PD deficiency-induced hemolysis. RESULTS: 308 children (64.3% male and 35.7% female) were included in this study. The most common complaint was jaundice (82.5%) and the most common cause of hemolysis was the intake of fava bean (85.7%). 68% of the children were treated with hydration/fluid therapy. Blood transfusion was conducted in 36.36% of the cases and the mean of blood administered was 18.9 cc/kg. CONCLUSION: In this study, hydration therapy was performed in most of the children presenting favism. Also, the incorrect calculation of the amount of blood needed for transfusion increased the frequency of blood transfusions and prolonged hospitalization time.

A novel G6PD gene variant in a Chinese girl with favism.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The human G6PD gene is highly polymorphic, and over 200 mutations have been identified, many of which are associated with hemolytic anemia. Here, we analyzed the clinical genetics data of a Chinese girl with favism who developed acute hemolytic anemia after fava bean ingestion. METHODS: The clinical genetics data of the proband who developed acute hemolytic anemia were collected and analyzed, and G6PD gene exons were sequenced in the proband and her family. RESULTS: We reported for the first time a novel G6PD gene variant in a Chinese girl, which we named "G6PD Wuhan." This variant is localized exon 3 of the G6PD gene at genomic position 141G > C, that is a change from p.Lys47 to Asn. The bioinformatics analysis and protein modeling study indicated this variant may have negative effects on the enzyme activity of G6PD. CONCLUSIONS: Our results indicated that favism in the proband was caused by this novel heterozygous variant (c.141G > C) in G6PD. The variant in G6PD has implications for genetic counseling and could provide insights into the functional roles of G6PD mutations.

Pattern of Hemolytic Anemia Among Egyptian Pediatric Emergency Department Patients.

OBJECTIVES: The emergency department is considered the backbone of the medical service offered in any hospital. Yet, the data on the frequency of pediatric hematological presentation is scanty. Anemia occurs in 9% to 14% of pediatric emergency department (ED) patients. Glucose-6-phosphate dehydrogenase (G6PD) deficiency affects more than 400 million people worldwide. Unfortunately, we do not have screening program for G6PD deficiency in Egypt. The aim of this study is to assess the burden of hemolytic crisis among Egyptian children visiting ED. METHODS: This is a prospective cross-sectional study among children presenting with acute hemolytic crisis in the ED of New Children Hospital, Cairo University from March to June 2016. Cases underwent full history taking, clinical examination, and laboratory tests based on clinical judgment of the resident. We categorized the presenting hemolytic anemias into 3 groups: G6PD deficiency, acute hemolysis in previously diagnosed patients with chronic hemolytic anemia, and acute undiagnosed hemolytic anemia. RESULTS: Our study included 143 patients, 109 males (76.22%) and 34 females (23.76%), with a mean age 36 months (range, 3-188 months), who presented with hemolytic anemia in the ED. Seventy-six cases (53.1%) were diagnosed as G6PD deficiency, 36 (25.2%) were diagnosed as chronic hemolytic anemia, and 31 (21.7%) were diagnosed as undiagnosed acute hemolytic anemia. CONCLUSIONS: Hemolytic anemia is very common presentation in ED. G6PD deficiency is the most common cause, representing 53.1% of the hemolytic anemia.

Leukocytosis in patients with favism and association with blood transfusion.

INTRODUCTION: Leukocytosis is a condition marked by abnormal increase in leukocyte count due to an inflammatory response as a defense against most of the infections, or bone tumors; including leukemia. The aim of this study is to analyze the effect of blood transfusion in leukocytosis patients with favism as compared to patients treated with antibiotics or combination of both. METHODS: A total of 97 patients with favism who were referred to the University hospital in 2016-2017 were studied. KEY FINDINGS: These patients experienced acute hemolysis following beans meal. These patients were either treated with blood transfusion, antibiotics or combination of both. CONCLUSIONS: This study shows that blood transfusion is an effective therapeutic option for the treatment of leukocytosis. Antibiotics are not deemed necessary for the treatment and blood transfusion alone, can decrease leukocytes to the normal level.

Intestinal transcriptional profiling reveals fava bean-induced immune response in DBA/1 mice.

BACKGROUND: Fava beans (FBs) have long been used as food, and their principal disadvantage is derived from their haemotoxicity. We hypothesized that FB ingestion alters the intestinal gene expression pattern, thereby inducing an immune response. RESULTS: In-depth sequence analysis identified 769 differentially expressed genes (DEGs) associated with the intestine in FB-treated DBA/1 mouse intestines. The identified genes were shown to be associated with biological processes (such as response to stimulus and immune system processes), human disease pathways (such as infectious diseases, endocrine and metabolic diseases, and immune diseases), and organismal system pathways (such as the digestive system, endocrine system, environmental adaptation, and immune system). Moreover, plasma total immunoglobulin E (IgE), histamine, interleukin (IL)-4 and IL-13 levels were significantly increased when the mice were treated with FBs. CONCLUSIONS: These results demonstrated that FBs affect the intestinal immune response and IgE and cytokine secretion in DBA/1 mice.

Anemia hemolítica, causa no habitual pero tampoco rara / Haemolytic anemia, unusual cause but not rare

La anemia es la disminución de la masa eritrocitaria, del hematocrito o de la concentración de hemoglobina en sangre por debajo de dos desviaciones estándar para la edad, sexo y raza. La etiología de la anemia varía según la edad. Las causas de anemia pueden ser clasificadas en tres grandes grupos: por pérdidas sanguíneas, por destrucción de hematíes (anemia hemolítica) y por falta de producción. La causa más frecuente de hemólisis por problema estructural de membrana es la esferocitosis y la causa más frecuente por déficit enzimático es el déficit de glucosa-6-fosfato-deshidrogenasa, seguido del de piruvato quinasa

Anemia is the decrease in erythrocyte mass, hematocrit, or blood hemoglobin concentration below two standard deviations for age, sex and race. The etiology of anemia varies according to age and can be classified into three groups: blood loss, destruction of red blood cells (hemolytic anemia) and failure to produce. The most frequent cause of hemolysis due to a structural membrane problem is spherocytosis and the most frequent cause of enzyme deficiency is glucose-6 phosphate dehydrogenase deficiency followed by the pyruvate kinase deficiency

Intestinal transcriptional profiling reveals fava bean-induced immune response in DBA/1 mice

BACKGROUND: Fava beans (FBs) have long been used as food, and their principal disadvantage is derived from their haemotoxicity. We hypothesized that FB ingestion alters the intestinal gene expression pattern, thereby inducing an immune response. RESULTS: In-depth sequence analysis identified 769 differentially expressed genes (DEGs) associated with the intestine in FB-treated DBA/1 mouse intestines. The identified genes were shown to be associated with biological processes (such as response to stimulus and immune system processes), human disease pathways (such as infectious diseases, endocrine and metabolic diseases, and immune diseases), and organismal system pathways (such as the digestive system, endocrine system, environmental adaptation, and immune system). Moreover, plasma total immunoglobulin E (IgE), histamine, interleukin (IL)-4 and IL-13 levels were significantly increased when the mice were treated with FBs. CONCLUSIONS: These results demonstrated that FBs affect the intestinal immune response and IgE and cytokine secretion in DBA/1 mice.

Hemolysis and Glucose-6-Phosphate Dehydrogenase Deficiency-Related Neonatal Hyperbilirubinemia.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency affecting more than 300 million individuals worldwide. Extreme neonatal hyperbilirubinemia, with its severe sequelae of bilirubin neurotoxicity and the potential of death, is the most devastating manifestation of G6PD deficiency. In a recent review of Favism, Luzzatto and Arese state that the pathophysiology of jaundice in G6PD-deficient neonates is different from that of favism, as there is little evidence of hemolysis in these infants. OBJECTIVES: To explore the role of hemolysis in neonatal hyperbilirubinemia associated with G6PD deficiency. METHODS: Previously published works including studies of endogenous production of carbon monoxide (CO), an index of heme catabolism, in hyperbilirubinemic G6PD-deficient neonates were reviewed to determine the role of hemolysis in this condition. RESULTS: Three studies demonstrated that endogenous CO production is elevated in G6PD-deficient neonates with extreme hyperbilirubinemia. CONCLUSIONS: Hemolysis is an important pathogenetic factor in G6PD deficiency-associated neonatal hyperbilirubinemia.

A practical toxicity bioassay for vicine and convicine levels in faba bean (Vicia faba).

BACKGROUND: Faba bean (Vicia faba) vicine and convicine (V-C) aglycones (divicine and isouramil respectively) provoke an acute hemolytic anemia called favism in individuals with a glucose-6-phosphate dehydrogenase (G6PD) enzyme defect in their red blood cells. Geneticists/plant breeders are working with faba bean to decrease V-C levels to improve public acceptance of this high-protein pulse crop. Here, we present a fast and simple ex vivo in vitro bioassay for V-C toxicity testing of faba bean or faba bean food products. RESULTS: We have shown that 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)-treated (i.e., sensitized) normal red blood cells, like G6PD-defective blood, displayed (i) continuous glutathione (GSH) depletion with no regeneration as incubation time and the dose of aglycones increased, (ii) progressive accumulation of denatured hemoglobin products into high molecular weight (HMW) proteins with increased aglycone dose, (iii) both band 3 membrane proteins and hemichromes, in HMW protein aggregates. We have also demonstrated that sensitized red blood cells can effectively differentiate various levels of toxicity among faba bean varieties through the two hemolysis biomarkers: GSH depletion and HMW clumping. CONCLUSION: BCNU-sensitized red blood cells provide an ideal model for favism blood, to assess and compare the toxicity of faba bean varieties and their food products. © 2018 Society of Chemical Industry.