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.

Glucose-6-phosphate Dehydrogenase Deficiency / 임상소아혈액종양

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder. There are more than 400 million people worldwide with G6PD deficiency, and its distribution is similar to that of malaria. G6PD deficiency is an X-linked recessive disorder. Most patients with G6PD deficiency may be asymptomatic throughout their lives. They may present as neonatal jaundice, or acute and chronic hemolysis. The most important point in the management of G6PD deficiency is to avoid oxidative stress. The prevalence of G6PD deficiency in Korea is about 0.9%. However, a nationwide survey has revealed that the number of patients with enzymopathy is increasing. Immigration of different ethnicities into Korea, and the rise of interracial marriages will likely lead to an increase in the number of patients with G6PD deficiency.

Glucose-6-phosphate Dehydrogenase Deficiency / 임상소아혈액종양

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder. There are more than 400 million people worldwide with G6PD deficiency, and its distribution is similar to that of malaria. G6PD deficiency is an X-linked recessive disorder. Most patients with G6PD deficiency may be asymptomatic throughout their lives. They may present as neonatal jaundice, or acute and chronic hemolysis. The most important point in the management of G6PD deficiency is to avoid oxidative stress. The prevalence of G6PD deficiency in Korea is about 0.9%. However, a nationwide survey has revealed that the number of patients with enzymopathy is increasing. Immigration of different ethnicities into Korea, and the rise of interracial marriages will likely lead to an increase in the number of patients with G6PD deficiency.

Deficiencia de glucosa 6 fosfato deshidrogenasa en niños: caso clínico / Glucose-6-phosphate dehydrogenase deficiency in children: a case report

Introduction: Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is the most common red blood cell (RBC) enzyme disorder. The decrease as well as the absence of the enzyme increase RBC vulnerability to oxidative stress caused by exposure to certain medications or intake of fava beans. Among the most common clinical manifestations of this condition, acute hemolysis, chronic hemolysis, neonatal hyperbilirubinemia, and an asymptomatic form are observed. Objective: To analyze the case of a child who presented hemolytic crisis due to favism. Case report: A 2 year and 7 month old boy with a history of hyperbilirubinemia during the newborn period with no apparent cause, no family history of hemolytic anemia or parental consanguinity. He presented a prolonged neonatal jaundice and severe anemia requiring RBC transfusion. An intake of fava beans 48 h prior to onset of symptoms was reported. G6PD qualitative determination was compatible with this enzyme deficiency. Conclusion: G6PD deficiency can be highly variable in its clinical presentation, so it is necessary to keep it in mind during the diagnosis of hemolytic anemia at any age.

Introducción: La deficiencia de la glucosa 6-fosfato deshidrogenasa (G6PD) es el trastorno enzimático más frecuente del glóbulo rojo (GR). Tanto la disminución como la ausencia de la enzima aumentan la vulnerabilidad del GR al estrés oxidativo provocado por algunos fármacos o la ingesta de habas. Sus manifestaciones clínicas más frecuentes son hemolisis aguda, hemolisis crónica, hiperbilirrubinemia neonatal, y una forma asintomática. Objetivo: Presentar el caso de un niño que debutó como crisis hemolítica debida a favismo. Caso clínico: Varón 2 años 7 meses con antecedente de hiperbilirrubinemia en el período neonatal sin causa evidente, sin historia familiar de anemia hemolítica ni de consanguinidad paterna. Debutó con un cuadro de ictericia y anemia severa que requirió transfusión de GR. Como antecedente anamnéstico se detectó la ingesta de habas 48 h previo al inicio de los síntomas. La determinación cualitativa de G6PD fue compatible con deficiencia de esta enzima. Conclusión: La deficiencia de G6PD puede ser muy variable en su expresión clínica, por lo cual es necesario tenerla presente dentro del diagnóstico diferencial de las anemias hemolíticas a toda edad.

Insuficiencia renal aguda secundaria como manifestación inicial de favismo en un adulto mayor: Caso clínico / Favism presenting as an acute renal failure: Report of one case

Background: We report a 67-year-old man presenting with abdominal pain of acute onset, pallor, jaundice and behavioral changes after ingestion of fava beans. In the initial evaluation he appeared acutely ill and had resting dyspnea, edema and jaundice. His initial laboratory assessment disclosed azotemia, elevated lactate dehydrogenase levels, a low hemoglobin concentration (4.9 /dL) and a high corrected reticulocyte count (4,7%) with negative direct and indirect Coombs' test. The patient was transferred to the ICU, where he received support therapy with hemodialysis, mechanical ventilation, vasoactive drugs and transfusions of packed red cells. The evolution after 1 month was favorable and he was discharged without anemia and with normal renal function. Three months after discharge, the glucose-6-phosphate-dehydrogenase screening study did not demonstrate detectable enzymatic activity.

Molecular basis of G6PD deficiency: Current status and its perspective

Glucose-6-phosphate dehydrogenase is an essential enzyme to cell growth. Its deficiency of enzyme plays an important role in senescence and death signaling. Also, it is actually the most common clinically important enzyme defect, not only in hematology, but also among all human known diseases. Clinical consequences of enzyme deficiency are: neonatal hyperbilirubinemia, acute hemolytic anemia, and chronic hemolytic anemia. The enzyme gene spans 18 kb on the X chromosome [xq28] and contains 13 exons. Its promoter is embedded in a CpG island that is conserved from mice to humans. The development of a number of PCR-based methods for the detection of known mutations in Glucose- 6-phosphate dehydrogenase has made it possible to detect enzyme deficiency and identify the specific mutation responsible with relative ease. We will discuss the mentioned clinical manifestations of glucose-6-phosphate dehydrogenase deficiency, Genetics, biochemistry and pathophysiology of the enzyme in details using newer published data and present most of the studies in Iranian population

Evaluation of some toxic effects of the glycoside convicine on albino rat

Isouramil [IU] is a glycone of the glycoside convicine isolated from faba beans [Vacia faba L.]. Convicine caused haemolytic crisis called Favism especially in patients deficient in glucose-6-phosphate dehydrogenase. In the present study the experiments were performed to investigate the convicine effect on albino rats. Three groups of albino rats were used. The first group was kept as a control, the second and third group were given oral dose of convicine [2 mg/100g b.wt.] for 15 and 30 days, respectively. The results revealed that convicine caused significant decrease [P < 0.05] in red blood cells. R.B.Cs and hemoglobin content. The analysis of serum albumin/globulin ratio a showed significant decrease [P < 0.05]. There were significant increases [P < 0.05] in serum and tissue total protein, serum bilirubin, globulin and iron. The results showed that convicine when hydrolyzed to its haemoglobin aglycon isouramil caused the same signs similar in many respects to those observed in human metabolic disease [Favism]

Glucose-6-phosphate dehydrogenase activity in Jordanian female children with acute hemolytic crises

The study objective is to determine the mode of inheritance in Glucose-6-Phosphate Dehydrogenase [G6PD]-deficient female children who have a history of acute hemolytic crises. Also, it aims to study the relationship between the type of inheritance and the severity of hemolysis, and to determine the factors incriminated in provoking hemolytic crises on them. The study included 40 female children with confirmed diagnosis of G6PD deficiency who were admitted to Princess Rahma Teaching Hospital with acute hemolytic crisis between June 2002 and April 2005. G6PD enzyme levels were studied in their mothers and in thirty-seven fathers to determine the mode of inheritance. In addition, 45 unaffected volunteers were evaluated as a control group. The results showed that 65% were heterozygous females and 35% were homozygous for G6PD deficiency. The mean G6PD level for homozygous females was 4.79 +/- 2.67 mU/10[9] RBCs compared to 54.1 +/- 23.2 mU/10[9] RBCs in heterozygous females. In 92.5% of children there was a history of fava beans ingestion before crisis. The mean time for appearance of symptoms after ingestion of fava beans was 10.57 +/- 4.99 hours compared to 23.77 +/- 5.23 hours in heterozygous females, and the duration of hemolytic crises was higher in homozygous females: 78 +/- 12.2 hours compared to 53 +/- 10 hours in heterozygous females. Two breast-feed infants gave history of fava beans ingestion by their mothers before crisis. This study demonstrated that females with G6PD activity level of less than 10% are usually homozygous females with rapid onset of symptoms and longer duration of hemolytic crisis following exposure to triggering factors, especially uncooked green beans, whose metabolites may be excreted in breast milk

Glucose-6-phosphate dehydrogenase G6PD deficiency

Glucose-6-phosphate dehydrogenase deficiency, the most worldwide common enzyme deficiency, causes a spectrum of diseases including neonatal hyperbilirubinemia, acute and chronic hemolysis. Persons with this condition also may be asymptomatic. This X-linked inherited disorder most commonly affects persons of African, Asian, Mediterranean, or middle-Eastern descent. Approximately 400 million people are affected in the world. Prevalence of G6PD deficiency in Tehran was 2.1% [3.6% boys- 0.6% girls] in Babol [12.5% boys, 4.1% girls] in Sari [14.3% boys, 3% girls]. This condition usually is diagnosed by fluorescent spot test. Different gene mutation different levels of enzyme deficiency, with classes assigned to various degrees of deficiency and disease manifestation. Acute hemolysis is usually caused by exposure to an oxidative stressor in the form of oxidative drug or fava beans and is self-limited, but in rare instances it can be severe enough to warrant a blood transfusion. Neonatal hyperbilirubinemia may require treatment with phototherapy or exchange transfusion to prevent kernicterus. Variant that causes chronic hemolysis is uncommon and is related to sporadic gene mutations. The prevalence of molecular mutation varied in north of Iran, Mazandaran [66.25% Mediterranean, 27% Cantham and 6.75% Cosensa]. Gilan [86.4% Mediterranean, 9.7% Cantham], Golestan [69% Mediterranean, 2.67% Cantham]. The most important way for prevention is screening of neonate for G6PD deficiency and avoidance of exposure to oxidant agent, Fava bean and also early treatment of neonatal jaundice

Deficiencia de glucosa 6-fosfato deshidrogenasa. Aspectos generales de la eritroenzimopatía más frecuente en el mundo / Defficiency of glucose 6-phosphate dehydrogenase. General aspects of the world's most frequent erithroenzimopathy

La deficiencia de la enzima glucosa 6-fosfato deshidrogenasa (G6PD) es la eritroenzimopatía congénita más frecuente en el mundo y se caracteriza por ictericia neonatal (esta enfermedad es asintomática hasta que el portador entra en conctacto con una sustancia de poder oxidante), anemia hemolítica aguda y autolimitada y favismo. Una gran variedad de drogas e infecciones pueden causar anemia hemolítica en las personas con esta deficiencia y las secuelas no hematológicas son bien conocidas. Mediante la caracterización bioquímica establecida por la Organización Mundial de la Salud (OMS), se han documentado a lo largo de diferentes poblaciones en el mundo más de 400 variantes de G6PD; sin embargo, cuatro de ellas se encuentran presentes en la mayoría de las poblaciones: variante A, A-,B y mediterránea. Las técnicas de biología molecular han permitido identificar las mutaciones y/o polimorfismos presentes en el gen que codifica para esta enzima. La distribución de la deficiencia en diferentes poblaciones ha sido investigada exhaustivamente y frecuencias génicas de alrededor de 1,5 porciento se han observado en algunos grupos étnicos, esto ha contribuido no sólo al conocimiento de la enfermedad, sino ha sido relevante en estudios de genética de poblaciones.

Comparative study for the detection of 563 C-T G6PD mutation using restriction enzyme assay and amplification and refractory mutation system [ARMS]

G6PD deficiency is the most common enzyme disorder in humans and is characterized by considerable biochemical and molecular heterogeneity. The prevalence of G6PD deficiency in the Middle East varies greatly, ranging from 1% among Egyptians to 11.5% among Iranians. G6PD Mediterranean [563 C-T] mutation is probably the most common G6PD variant in the world. The relative frequency of this mutation ranges from 70% among Egyptians to 97% for Kurdish Jews. This study was conducted on 30 Egyptian pediatric G6PD-deficient patients. Quantitation of G6PD enzyme was performed before molecular analyses, during, and one month after the hemolytic attack. The frequency of the mutation was investigated using two methods; the reference method; RFLPs and ARMS technique. The aim of this study was to compare both methods. Both methods gave identical results, yet ARMS method is easier and less time consuming

[Prevalence of G6PD deficiency among primary school students in Amol]

G6PD [glucose-6-phosphate dehydrogenase] deficiency is the most common enzyme deficiency in human beings. Using fava beans, some drugs and oxidant agents cause life-threatening hemolysis in children and other ages. The aim of this study was to determine the prevalence of G6PD deficiency and its relation to age and family history. This cross sectional, descriptive and analytical study was performed on 732 persons. Students aged between 7-11 years old were randomly chosen by cluster sampling method. Data were analyzed by SPSS. For comparing enzyme deficiency between two sexes and the effect of family history, chi square test was used. From 732 students, 295 were male and 437 were female. 11.2% of males and 1.4% of females were G6PD deficient that this difference was considered significant [p<0.0001]. Children who have G6PD deficiency, history of G6PD deficiency among their family members was significantly more [p<0.0001]. Due to high prevalence of G6PD deficiency as a threatening factor for public health in north of Iran, it is suggested cord blood G6PD screening be considered at birth especially in male neonates and the quality of primary health care and public information be increased by teaching

Red cell glucose-6-phosphate dehydrogenase phenotypes in Iraq

We attempted to characterize biochemically glucose-6-phosphate dehydrogenase [G6PD] variants in Iraqi individuals. Thus 758 healthy Iraqi males aged 18-60 years were randomly selected and 46 [6.1%] were G6PD deficient. Although the predominant non-deficient G6PD phenotype was G6PD B [92.6%], G6PD A+ was found in polymorphic frequency [1.3%]. In the deficient group, 31 cases were fully characterized, including 17 cases with features consistent with G6PD Mediterranean variant, while 12 had other biochemical features and were labelled as non-Mediterranean variant. The remaining two deficient cases were characterized as G6PD A- variant. The presence of a significant number of non-Mediterranean variant was unexpected and may be related to the more heterogeneous background of the Iraqi people

Clinical profile of children with favism

To describe the clinical picture of under five year children with favism including the severity of the disease and its treatment. The seasonal pattern is also examined. Design: Case series that reflects the investigator's own experience in handling cases of favism. Setting: Al-Khansah Maternity and Children Hospital in Mosul. All the cases are children with favism who were admitted to this main sick children hospital in Mosul during the period of one year from June 1992 to May 1993. Participants: Eighty-eight under five years old children of both sexes admitted to the hospital with favism. Clinical parameters measured: These children were managed as inpatients; being a retrospective study from their case records the following parameters were extracted: age, sex, date of onset [months], signs and symptoms, laboratory investigations and treatment given. The majority of cases [68%] were toddlers [one-four years], male: female ratio was 3: 4. All 88 children had dark colored urine and pallor. Jaundice was present in 3/4 of them while fever and vomiting were present in about half of the children. The months of April and May had witnessed the peak of the cases there was a second but less obvious peak in December. Six out of every ten patients were cases that required the ingestion of fava beans for several times before the acute hemolytic episode became clinically overt, while three out of ten children had the haemolysis after ingesting the beans for the first time. In one out of every ten children the present crisis was a recurrent one. One third of the children had a haemoglobin level of less than 5 g/dl, while in 77% of the cases the level was less than 7g/dl. Serum total bilirubin mainly of the indirect one was high in all patients and ranged between 1.2 - 28.2 mg /dl, the blood urea and serum creatinine values were normal. All patients needed and received blood transfusion. All of them recovered within 2-3 days without complications. The ingestion or inhalation of fava beans by susceptible under five years children in northern Iraq appear to precipitate a severe haemolytic crisis which usually needs blood transfusion. To prevent such episodes early detection - during neonatal period - of glucose 6-phosphate dehydrogenase [G6PD] deficiency is called for

G6PD deficiency and fava bean consumption do not produce hemolysis in Thailand.

Favism, a hemolytic condition associated with fava bean consumption among the glucose-6-phosphate dehydrogenase (G6PD) deficient persons, is well described in the Middle East and Mediterranean areas. However, it is not well documented among the Thais or other Southeast Asians. It is possible that it does exist but that hemolysis which develops is of very minor degree and thus escapes clinical detection. This cross-sectional study hypothesizes that if the fava bean and G6PD deficiency interact in the Thai population, they should cause a significant difference in hematocrit level. The study was carried out in a community hospital in a malaria endemic area. We found that there was a trivial difference of the hematocrit (approximately 1%) which was too small to warrant any clinical significance after controlling for the extraneous effects of age, sex, use of malaria chemoprophylaxis, falciparum infection, use of analgesics/antipyretics and admission status of the patients (p = 0.668). This may be due to the presence of different G6PD mutants to those found elsewhere or due to different consumption patterns of fava beans among the Thais compared to people in other areas with high prevalence of G6PD deficiency.