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Background: Glucose 6 phosphate dehydrogenase ( G6PD) is a rate-limiting enzyme of the pentose phosphate pathway. The loss of G6PD activity in red blood cells increases the risk of acute haemolytic anaemia under oxidative stress induced by infections, some medications, or fava beans. More than 200 single missense mutations are known in the G6PD gene. A 41-year-old woman with a family history of favism coming from the Basilicata region (Italy) was evaluated at our hospital for G6PD abnormalities. Methods: DNA was extracted from a peripheral blood sample and genotyped for the most common G6PD pathogenic variants (PVs). Positive results obtained by Restriction Fragment Length Polymorphism ( RFLP ), as per practice in our laboratory, were then reconfirmed in Sanger sequencing. Results: RFLP analysis highlighted a variant compatible with the G6PD Cassano variant. Confirmatory testing by Sanger unexpectedly identified a novel variant: c.1357G>A, p.(Val453Met) (NM_001360016.2); the same variant was found in the patient's mother. In silico models predicted a deleterious effect of this variant at the protein level. The novel G6PD variant was named " G6PD Potenza " on the basis of the patient's regional origin. Conclusions: This case describes a novel G6PD variant. It also highlights how the Sanger sequencing technique still represents an indispensable confirmatory standard method for variants that could be misinterpreted by only using a "first-level" approach, such as the RFLP . We stress that the evaluation of clinical manifestations in G6PD-deficient patients is of primary importance for the classification of each new G6PD mutation, in agreement with the new WHO guidelines.

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.

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., (© 2020 Society of Chemical Industry.)

Favism is an acute hemolytic syndrome caused by the ingestion of fava bean (FB) in glucose 6-phosphate dehydrogenase (G6PD) deficient individuals. However, little is known about the global transcripts alteration in liver tissue after FB ingestion in G6PD-normal and -deficient states. In this study, deep sequencing was used to analyze liver genes expression alterations underlying the effects of FB in C3H (Wild Type, WT) and G6PD-deficient (G6PDx) mice and to evaluate and visualize the collective annotation of a list of genes to Gene Ontology (GO) terms associated with favism. Our results showed that FB resulted in a decrease of glutathione (GSH)-to-oxidized glutathione (GSSG) ratio and an increase of malondialdehyde (MDA) both in the G6PDx and WT-control check (CK) mice plasma. Significantly, liver transcript differences were observed between the control and FB-treated groups of both WT and G6PDx mice. A total of 320 differentially expressed transcripts were identified by comparison of G6PDx-CK with WT-CK and were associated with immune response and oxidation-reduction function. A total of 149 differentially expressed genes were identified by comparison of WT-FB with WT-CK. These genes were associated with immune response, steroid metabolic process, creatine kinase activity, and fatty acid metabolic process. A total of 438 differential genes were identified by comparing G6PDx-FB with G6PD-CK, associated with the negative regulation of fatty acid metabolic process, endoplasmic reticulum, iron binding, and glutathione transferase activity. These findings indicate that G6PD mutations may affect the functional categories such as immune response and oxidation-reduction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common genetic abnormality known to predispose to acute hemolytic anemia (AHA), which can be triggered by certain drugs or infection. However, the commonest trigger is fava beans (Vicia faba) ingestion, causing AHA (favism), which may be life-threatening especially in children. G6PD deficiency is genetically highly heterogeneous, as nearly 200 different mutations have been observed. We have investigated the hematological features of acute favism in the Palestinian Gaza community that is characterized by the polymorphic coexistence of three different G6PD deficiency genes (G6PD A-, G6PD Cairo, G6PD Med). We have found by comparison to the general population (485 adults and 466 newborns) that children with favism, in terms of relative frequency, G6PD A- was under-represented, whereas G6PD Med was over-represented. We also found that the severity of anemia was significantly greater with G6PD Med and G6PD Cairo than with G6PD A-; and with G6PD Cairo, compared to the other two variants, there was greater hyperbilirubinemia, as well as persistence of mild anemia and reticulocytosis for as long as 4months after recovery from favism. This is the first report determining a differential impact of different G6PD mutations on the clinical features of favism in the same population and the same environment., (Copyright © 2016. Published by Elsevier Inc.)

Objectives: Identify and screen the G6PD Mediterranean mutation in favism patients by applying a Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR)., Patients and Methods: A total of 114 unrelated Egyptians patients were included in the present study; their ages ranged between (2-9) years with male to female ratio 4.5:1. G6PD activity was determined qualitatively from red cell hemolysate during attack. The G6PD Mediterranean mutation in patients has been identified by ARMS-PCR., Results: G6PD deficiency was detected in 87.7%, (n=100). The frequency of G6PD Mediterranean mutation was (94.7%), (n=108). The association between G6PD deficiency and Mediterranean mutation was a highly significant., Conclusions: Glucose-6-phosphate dehydrogenase Mediterranean mutation is one of the most common mutations causing G6PD deficiency among Egyptian children with favism.

Background and Objectives: The etiology of favism remains unclear and the fate of favic patients has not previously been studied. Therefore, individuals who had experienced an episode of favism were studied regarding subsequent fava bean ingestion, including the reason for fava bean ingestion after the initial favic attack and any adverse reactions. In addition, a new hypothesis for the etiology of favism is proposed., Patients and Methods: From June 2005 to June 2012, a total of 38 patients with a history of favism were included in this study. Circumstances regarding the initial favic attack were obtained from medical records and patient interviews, and subsequent fava bean ingestion and recurrence of symptoms were investigated., Results: Three of the 38 patients (7.9%) were female, and 35 (92.1%) were male. The mean age was 27.9 years (14-63 years). The first attack of favism occurred before 10 years of age for 31 patients (81.6%) and in the springtime for 35 patients (92.1%). Thirty-three patients (86.7%) regularly ate fava beans before the attack, and 35 (92.1%) resumed eating fava beans within 1-17 years after the attack without symptoms. Two patients (5.2%) experienced a single recurrence of symptoms. No evidence of hemolysis was found in the four patients checked after fava bean re-ingestion., Conclusions: Patients resumed eating fava bean for various reasons, and the recurrence of symptoms was uncommon. An infectious agent such as a virus may play a role in the development of favism., (Copyright © 2013 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.)

Fabry disease is an X-linked lysosomal disease caused by mutations of the alpha-galactosidase A (GLA) gene at chromosome subband Xq22.1. To date, more than 600 genetic mutations have been identified to determine the nature and frequency of the molecular lesions causing the classical and milder variant phenotypes and for precise carrier detection. We report here a Fabry family (mother, son and daughter) where the alpha-galactosidase A defect was associated with a glucose-6-phosphate dehydrogenase (G6PD) deficiency. Mutation analysis revealed for the GLA gene the presence of a new mutation, i.e., a small deletion (c.452delA) on exon 3 and for the G6PD gene the presence of 2 mutations, p.V68M (G6PD Asahi, G6PD A+) and p.N126D (G6PD A+) on exon 3 and exon 4, respectively.

An association between favism (a hemolytic reaction to consumption of fava beans), glucose-6-phosphate dehydrogenase deficiency (G6PD(-)) and acid phosphatase locus 1 (ACP(1)) phenotypes has been reported; the frequency of carriers of the p(a) and p(c) ACP(1) alleles was found to be significantly higher in G6PD(-) individuals showing favism than in the general population. Here, we investigated the hypothesis that favism is caused by toxic Vicia faba substances, which in some ACP(1) phenotypes cause increased phosphorylation and consequently increased glycolysis, with strong reduction in reduced glutathione production, resulting in hemolysis. It has been demonstrated that ACP(1) f isoforms have physiological functions different from those of s isoforms and are responsible for most of the phosphatase activity, in addition to being less stable in the presence of oxidizing molecules. Thus, the C, CA and A phenotypes, characterized by lower concentrations of f isoforms, could be more susceptible to damage by oxidative events compared to the other phenotypes. To test this hypothesis, the (f+s) enzymatic activity of different ACP(1) phenotypes with and without added V. faba extract was analyzed. Enzymatic activities of ACP(1) A, -CA, -C groups (low activity) and -B, -BA, -CB groups (high activity) were significantly different after addition of V. faba extract. Phenotypes A, CA and C had extremely low enzymatic activity levels, which would lead to low levels of reduced glutathione and bring about erythrocyte lysis.

A 1-year-old Moroccan boy was referred because of jaundice. A peripheral blood smear showed 'blister cells'. This finding is characteristic for haemolysis caused by glucose-6-phosphate dehydrogenase deficiency. It appeared hemolysis occurred because the boy ate fava beans.

Objective: To evaluate the G6PD(C563T) Mediterranean mutation among Jordanian females who were admitted to Princess Rahma Teaching Hospital (PRTH) with/or previous history of favism., Study Design: A descriptive study., Place and Duration of Study: Jordanian University of Science and Technology and PRTH, from October 2003 to October 2004., Methodology: After obtaining approval from the Ethics Committee of Jordanian University of Science and Technology, a total of 32 females were included in this study. Samples from 15 healthy individual females were used as a negative control. Blood samples from these patients were collected and analyzed by allele-specific polymerase chain reaction (AS-PCR) to determine the G6PD(C563T) mutation., Results: Twenty one out of 32 patients were found to be G6PD(C563T) Mediterranean mutation (65.6%) positive. Three out of 21 patients were homozygous and remaining 18 were heterozygous for G6PD(C563T) Mediterranean mutation. Eleven (34.4%) out of 32 patients were found to be negative for G6PD(C563T) mutation indicating the presence of other G6PD mutations in the study sample., Conclusion: G6PD(C563T) Mediterranean mutation accounted for 65.6% of the study sample with favism in the North of Jordan. There is likely to be another G6PD deficiency variant implicated in acute hemolytic crisis (favism).

Introduction: Reduced concentrations of glucose-6-phospate dehydrogenase (G6PD) render erythrocytes susceptible to hemolysis under conditions of oxidative stress. In favism, the ingestion of fava beans induces an oxidative stress to erythrocytes, leading to acute hemolysis., Discussion: The simultaneous occurrence of methemoglobinemia has been reported only scarcely, despite the fact that both phenomena are the consequence of a common pathophysiologic mechanism. The presence of methemoglobinemia has important diagnostic and therapeutic consequences. We report a previously healthy boy who presented with combined severe hemolytic anemia and cyanosis due to methemoglobinemia, following the ingestion of fava beans. His condition was complicated by the development of transient acute renal failure. A G6PD-deficiency was diagnosed. We review the literature on the combination of acute hemolysis and methemoglobinemia in favism. Pathophysiologic, diagnostic, and therapeutic aspects of this disorder are discussed.

We describe the case of a 64-year-old patient with glucose-6-phosphate dehydrogenase deficiency who was referred to our hospital because of an acute inferior myocardial infarction.Given the possible risk of acute haemolytic anaemia, aspirin was not given in the acute phase, and the patient was successfully treated by balloon angioplasty of the right coronary artery.After functional and genetic testing showing the presence of the Mediterranean mutation, known to be a class II variant, the patient received oral daily aspirin (100 mg) under strict monitoring in order to promptly detect any sign of haemolysis. After 4 days, a complex percutaneous coronary intervention with an implantation of two drug-eluting stents was successfully performed on the left coronary artery. After 3 months, the patient is free from adverse events.Glucose-6-phosphate dehydrogenase deficiency is commonly considered a contraindication to aspirin intake; however, this case shows that aspirin at low, antiplatelet dosage is well tolerated and should not be denied to patients with ischaemic heart disease and complex coronary anatomy.

Screening of G6PD deficiency was carried out on 79 unrelated subjects (32 females and 47 males), all coming from out consultation. DNA from deficient subject (11 females and 30 males) was analyzed for the presence of G6PD mutation. Known mutations were studied by the appropriate restriction enzyme digestion of fragment amplified by PCR. Where the mutation could not be identified in this way, the samples were subjected to SSCP analysis and abnormal fragments were sequenced. Through these methods, seven different mutations have been identified. Among deficient females, eight had the African variant A-(tow of them were homozygous) and three had the Mediterranean variant, one of them was homozygous and have had a haemolytic crisis after ingestion of fava beans showing at birth manifestation of neonatal jaundice. Among deficient males, four were hospitalized and transfused after a haemolytic crisis due to ingestion of fava beans. All of them have had manifestation of neonatal jaundice. Of them, one carried the Mediterranean variant and three others had the African variant A-. Among the remaining deficient males, 15 had A-variant, two had the Aurès mutation. SSCP analysis of nine mild deficient males, revealed the presence of the association of 1311 CT/93 TC in two subjects, a newly described silent mutation in the exon 12 associated with the polymorphism in the intron 11 93 TC in one subject and tow single intronic base deletion. The first is IVS V 17 (-C) found in two subjects and the second is IVS VIII 43 (-G) encountered in four subjects.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Africa is of high prevalence, although precise data are lacking in many individual nations. We investigated 129 unrelated subjects (71 male subjects, 58 female subjects) visiting a teaching hospital in Freetown, Sierra Leone, to collect baseline data on the distribution of G6PD deficiency among respective ethnic groups in the country. We confirmed eight G6PD-deficient male subjects by two formazan-based blood tests (11.3% of the male subjects examined), and also detected the common 376A > G mutation in 11 male subjects and eight female subjects by sequencing exons 3-5 of the G6PD gene. Selected samples were further sequenced for exons 2-13 and introns 5, 7, 8, and 11. Among the deficient male subjects, six were G6PD A- carrying the double mutations (202G > A and 376A > G), all of whom were in the Temne and Mende ethnic groups. Others included A- Betica, and a novel variant having double mutations in exon 5 (311G > A and 376A > G forming 104 Arg > His and 126 Asn > Asp, respectively), which we designate as G6PD Sierra Leone. Subsequent haplotype analysis linked this novel variant to the G6PD A- "family".

Background: The aim of this study was the molecular analysis of G6PD patients for G6PD mutations in the coastal provinces of the Caspian Sea in north of Iran., Methods: Studies on G6PD deficiency in the coastal provinces of the Caspian Sea in Iran were performed in 248 patients with a history of favism, in Mazandaran, Golestan and Gillan provinces, which contributed 74, 71 and 103 samples, respectively. Three different major polymorphic variants were determined by molecular analysis, using SSCP, sequencing and PCR-RFLP methods. Firstly, all Mazandaranian samples were searched for the Mediterranean mutation by PCR-RFLP method. The remaining samples of the Mazandaran province were analysed by SSCP followed by sequencing for other mutations. Then, our research was expanded in two other provinces, Golestan and Gillan, by the PCR-RFLP method., Results: Three different major polymorphic variants were found: G6PD Mediterranean 75.4% (187 out of 248), G6PD Chatham 19.76% (49 out of 248), G6PD Cosenza 2.02% (5 out of 248) and 7 samples out of 248 remained unknown. Also, there was no significant difference in the incidence of various G6PD polymorphic variants with mean age, and various blood work values such as Hb, WBC and MCV between two major variants (p>0.20)., Conclusions: These results which are the first molecular investigation in north of Iran indicate a higher prevalence of G6PD Chatham in this large Iranian population than anywhere else in the world. The distribution of these G6PD variants is more similar to that found in an Italian population (80-84% for Mediterranean, 20% for Chatham and 1.9% for Cosenza mutation). Although the origin of Iranian population is rather uncertain, the closer similarity of the mutation spectrum to Italian rather than Middle Eastern population may indicate that these populations have a common ancestral origin.

Hereditary glutathione reductase (GR) deficiency was found in only 2 cases when testing more than 15 000 blood samples. We have investigated the blood cells of 2 patients (1a and 1b) in a previously described family suffering from favism and cataract and of a novel patient (2) presenting with severe neonatal jaundice. Red blood cells and leukocytes of the patients in family 1 did not contain any GR activity, and the GR protein was undetectable by Western blotting. Owing to a 2246-bp deletion in the patients' DNA, translated GR is expected to lack almost the complete dimerization domain, which results in unstable and inactive enzyme. The red blood cells from patient 2 did not exhibit GR activity either, but the patient's leukocytes contained some residual activity that correlated with a weak protein expression. Patient 2 was found to be a compound heterozygote, with a premature stop codon on one allele and a substitution of glycine 330, a highly conserved residue in the superfamily of NAD(P)H-dependent disulfide reductases, into alanine on the other allele. Studies on recombinant GR G330A revealed a drastically impaired thermostability of the protein. This is the first identification of mutations in the GR gene causing clinical GR deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a frequent congenital human enzyme defect, is the most frequent cause of hemolytic anemia triggered by drugs or infectious diseases. Drugs which induce acute hemolysis in patients with G6PD deficiency are often used in anesthesia and perioperative pain therapy. Considering the fact that patients from geographic regions with a high prevalence of the disease are often treated in European hospitals, special attention should be paid to this problem. We report a case of a 30-year-old female patient with favism and review the disease and anesthesia-related implications.

In a study conducted at Songklanagarind Hospital in the south of Thailand, the subjects were 225 patients (210 boys and 15 girls) with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Favism was found in 3.6% of the G6PD-deficient children. Approximately one half of the G6PD-deficient patients with favism were younger than 2 years. Sudden onset of anemia was found within 1 to 3 days after ingestion of dried fava beans. The classic features of favism, which are pallor, hemoglobinuria, and jaundice, were detected in all cases. To characterize the known G6PD mutations in Thai children, molecular analysis was performed for 8 G6PD-deficient children with favism by a combination of polymerase chain reaction-restriction fragment length polymorphism analysis and amplification refractory mutation system analysis. The G6PD variants in these children were G6PD Kaiping 1388,G-->A; G6PD Mahidol 487,G-->A; G6PD Viangchan 871,G-->A; and uncharacterized mutation with silent mutation 1311,C-->T.

The case of a 44 year old Ashkenazi Jewish woman of Russian origin who presented with a typical clinical and haematological picture of favism is reported. There was initial difficulty in confirming glucose-6-phosphate dehydrogenase (G6PD) deficiency because the enzyme concentrations were normal at presentation, but later fell to a concentration compatible with heterozygosity for the Mediterranean type of G6PD deficiency. The diagnosis was also later confirmed by gene analysis. The reasons for the difficulties in the initial confirmation of the diagnosis and the normal G6PD enzyme activity at presentation are discussed.

Glucose 6-phosphate dehydrogenase is a highly polymorphic enzyme encoded by a human X-linked gene (Xq2.8). This enzyme catalyses the first step of pentose phosphate pathway, that converts glucose 6-phosphate to 6-phosphogluconate with production of NADPH2. G6PD deficiency is the most common human metabolic inborn error affecting more than 400 million people world wide. The main clinical manifestations are acute hemolytic anemia and jaundice, triggered by infection or ingestion of Fava beans or oxidative drugs. A predominant variant of G6PD named Mediterranean is often associated with favism. This has been evident in several countries including Northern coastal provinces of Iran. Other current variants are Chatham and Cosenza. Molecular identification of the most prevalent mutations in G6PD gene was carried out in 71 males and females with G6PD deficiency. They were from Iranian Northern province of Golestan. DNA was extracted from blood samples and analyzed for known G6PD mutation by PCR and restriction fragment length polymorphisms (RFLP) technique. Adapting this method, revealed that Mediterranean mutation at nt 563(C-->T) is predominant in the area (69%) and 26.7% of patients have Chatham mutation at nt 1003(G-->A). Findings indicate a higher prevalence of these mutations, in Golestan compared to Mazandaran (66.2% Mediterranean and 19% Chatham mutation) and Gilan (86.4% Mediterranean and 9.71% Chatham mutations). Cosenza mutation at nt 1376(G-->C), by PCR-RFLP technique was not found among other 3 samples (4.3%). The similarity of these results with mutations in Italy indicates probable existence of a common ancestral origin in the observed populations.

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.

A major challenge in the post-genomic era is to identify the physiological functions of genes and elucidate the molecular basis for human disease. Genetic polymorphisms offer a convenient avenue for these efforts by providing evidence for the involvement of a given gene in human pathophysiology. Here we review the current evidence linking the low-molecular-weight protein tyrosine phosphatase (LMPTP) to several common diseases, including allergy, asthma, obesity, myocardial hypertrophy, and Alzheimer's disease. Based on the known effects of the genetic polymorphisms on the alternative mRNA splicing and enzyme levels of LMPTP, we discuss the possible molecular mechanisms of LMPTP involvement in these diseases.

Objective: To identify glucose-6-phosphate dehydrogenase (G6PD) gene mutations in 23 patients with G6PD deficiency and to gain further understanding of the molecular and genetic background of G6PD gene in Yunnan province, China., Methods: The mutations located in exons 2-12 and in parts of introns of G6PD gene were analyzed by amplification refractory mutation system(ARMS), natural and mis-match primer PCR/restrict enzyme, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP ) analysis and automatic DNA sequencing., Results: Among these 23 samples, 5 different point mutations in G6PD gene were identified, and they constituted 5 genotypes. There were 7 Han and 3 Dai patients with G487A mutation, 7 cases with both intron 11 T93C and C1311T mutations, 4 cases with intron 5 636 or 637 T-->del mutation, 1 case with G871A mutation, and 1 case with G487A/T93C/C1311T mutation. Two haplotypes, 93C/1311T and 93C/1311T/487A were identified in Yunnan. A strong association was observed between C1311T and the Nla III restriction site produced by intron 11 T93C. The findings of the investigators on IVS-5 636 or 637T-->del in Chinese, on G871A in mainland of China, and on G487A in the Han people of Yunnan have not been reported previously., Conclusion: G6PD deficiency is very heterogenous in Yunnan; G487A is one of the common mutations in that province and may be of different origins. Possibly IVS-11 T93C mutation is of non-African origin. IVS-11 T93C and C1311T might jointly result in G6PD deficiency. The above data on G6PD gene mutation types could be useful for clinical diagnosis, prevention of G6PD deficiency, and researches in the origin and migration of minorities in Yunnan or other regions.

After ingesting fava beans, a 26-month-old Chinese-Japanese male infant showed a sickly complexion and yellowish-brownish skin and was hospitalized. Severe hemolytic anemia was observed on admission, and transfusion of 200 ml of packed red cells was required. Red cell enzyme assay revealed that the patient and the mother were deficient in glucose-6-phosphate dehydrogenase (G6PD). Subsequent molecular analysis showed that the patient had a missense mutation 1376 G to T (G6PD Canton) and his mother was a homozygote for the mutation. The patient was a son of a Chinese (Taiwanese) mother and a Japanese father. Although G6PD deficiency is rare in the original Japanese population, the number of "imported" cases could be rising rapidly. This is the first reported Japanese case of G6PD deficiency with G6PD Canton.

Glukose-6-phosphate dehydrogenase (G6PD) is essential in protecting the red cell from oxidative damage. We report a case of acute haemolysis in a child with G6PD deficiency. Because of the severity of the anaemia, the patient was treated with blood transfusions and recovered fully. There are two main variants of G6PD deficiency (the Mediterranean variant and variant A) with different clinical profiles. Acute haemolytic attacks are induced by certain drugs, by infections or, in the Mediterranean variant, by ingestion of fava beans (favism). Increased awareness of this condition is necessary in Denmark because of increased immigration.

DNA sequencing revealed seven different glucose-6-phosphate dehydrogenase (G6PD) mutations in G6PD deficient subjects from 10 Polish families. Among them we found two novel mutations: 679C-->T (G6PD Radlowo, class 2) and a 1006A-->G (G6PD Torun, class 1). Variant G6PD Radlowo was characterized biochemically. Both novel mutations were analyzed using a model of the tertiary structure of the human enzyme. The main chain of G6PD Torun is different from the wild-type G6PD. The remaining mutations identified by us in deficient Polish patients were: 542A-->T (G6PD Malaga), 1160G-->A (G6PD Beverly Hills), 1178G-->A (G6PD Nashville), 1192G-->A (G6PD Puerto Limon), and 1246G-->A (G6PD Tokyo). Variant Tokyo was found in four families. In one of them favism was the first clinical sign of G6PD deficiency and chronic nonspherocytic hemolytic anemia (CNSHA) was diagnosed later. Variants G6PD Nashville and G6PD Puerto Limon were accompanied by the silent mutation 1311C-->T of the G6PD gene., (Copyright 1999 Wiley-Liss, Inc.)

In two unrelated Spanish males with glucose-6-phosphate dehydrogenase (G6PD) deficiency and haemolytic anaemia, and two different novel point mutations in the G6PD gene, have been identified. A C to T transition at nucleotide 406 resulting in a (136) Arg to Cys substitution and a C to G transition at nucleotide 1155 resulting in a (385) Cys to Trp substitution. These two molecular defects have not been described before and are designated G6PD Valladolid 406 C-->T and G6PD Madrid 1155 C-->G. In vitro biochemical characterization of both mutant enzymes showed important differences in their molecular properties according to their different clinical behaviour. In G6PD Valladolid, the mutation of which is located in exon 5, the normal in vitro heat stability may explain its mild clinical expression (low-grade haemolysis interrupted by an acute haemolytic crisis at age 70). In G6PD Madrid, the mutation, located in exon 10, results in a deficient variant associated with neonatal jaundice and life-long chronic nonspherocytic haemolytic anaemia (CNSHA). This finding further emphasizes the importance of this specific region of the G6PD gene in the stabilization of the G6PD molecule. Putative relationships between these single point mutations and the molecular properties of the mutant enzymes are also discussed.

Human red cell acid phosphatase (ACP1) is a polymorphic enzyme closely related to cytosolic low molecular weight acid phosphatases, a protein family broadly conserved among eukaryotes. Two different functions have been proposed for ACP1: flavin mononucleotide (FMN) phosphatase and phosphotyrosine phosphatase (PTPase). Given that genetic variants of ACP1 activity are common, the enzyme could have a role in regulating a large spectrum of cellular functions and, in turn, disease susceptibility. In the present paper we report a study of ACP1 genetic polymorphism in 1088 normal subjects and in 1267 subjects from the population of Rome admitted to hospital for a number of common diseases. All ACP1 parameters investigated show highly significant differences among samples, suggesting that the enzyme may have a significant role in some of the diseases considered. In particular, consistent associations of ACP1 with developmental disturbances and with hemolytic favism have been observed. In the majority of diseases showing association with ACP1, only one of the two ACP1 isoforms, f and s, is involved, supporting the hypothesis of a functional differentiation between the two enzymatic fractions.

In order to explore the nature of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Spain, we have analysed the G6PD gene in 11 unrelated Spanish G6PD-deficient males and their relatives by using the polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) analysis combined with a direct PCR-sequencing procedure and PCR-restriction enzyme (RE) analysis. We have identified eight different missense mutations, six of which have been reported in previously described G6PD variants. In nine patients who had presented with acute favism we found the following mutations: G6PD A-376G-202A (four cases), G6PD Union1360T (two cases), G6PD Mediterranean563T (one case) and G6PD Aures143C (one case). In the remaining patient a novel A to G transition was found at nucleotide position 209 which has not been reported in any other ethnic group. This mutation results in a (70) Tyr to Cys substitution and the resulting G6PD variant was biochemically characterized and designated as G6PD Murcia. This new mutation creates a Bsp 1286I recognition site which enabled us to rapidly detect it by PCR-RE analysis. In two patients with chronic non-spherocytic haemolytic anaemia (CNSHA) we found the underlying genetic defects, as had been noted previously, to be located within a cluster of mutations in exon 10. One of them had the T to C transition at nucleotide 1153, causing a (385) Cys to Arg substitution, previously described in G6PD Tomah. The other, previously reported as having a variant called G6PD Clinic, has a G to A transition at nucleotide 1215 that produces a (405) Met to Ile substitution, thus confirming that G6PD Clinic is a new class I variant.

The electrophoretic mobility and level of enzyme activity of glucose-6-phosphate dehydrogenase (G6PD) was established in 100 unrelated Algerian males with G6PD deficiency. DNA from these subjects was analysed for the presence of certain known G6PD mutations by the appropriate restriction enzyme digestion of fragments amplified by the polymerase chain reaction. Where the mutation could not be identified in this way, the samples were subjected to single-strand conformation polymorphism analysis and abnormal fragments were sequenced. In this way, eight different mutations have been identified, of which five are polymorphic and account for 92% of the samples. The most common variants are G6PD A- (46%) and G6PD Mediterranean (23%), both of which were associated with favism. A new polymorphic variant, G6PD Aures, has been identified during the course of this study, whereas another, G6PD Santamaria, has now been established as a polymorphic variant (11%). Thus, G6PD deficiency in Algeria is heterogeneous, suggesting that there has been significant gene flow, both from sub-Saharan Africa and from other parts of the Mediterranean.

The cloning and sequencing of the normal glucose-6-phosphate dehydrogenase (G6PD) gene has led to the study of the molecular defects that determine enzymatic variants. In this paper, we describe the mutations responsible for the Ferrara I variant in an Italian man with a family history of favism, from the Po delta. Nucleotide sequencing of this variant showed a G-->A mutation at nucleotide 202 in exon IV causing a Val-->Met amino acid exchange, and a second A-->G mutation at nucleotide 376 in exon V causing an Asn-->Asp amino acid substitution. Although on the basis of its biochemical properties this variant was classified as G6PD Ferrara I, it has the same two mutations as G6PD A(-), which is common in American and African blacks, and as the sporadic Italian G6PD Matera. The mutation at nucleotide 202 was confirmed by NlaIII digestion of a polymerase chain reaction amplified DNA fragment spanning 109 bp of exon IV. The 109-bp mutated amplified sequence is not distinguishable from the normal sequence in single strand conformation polymorphism analysis.

As part of a study aiming to define the molecular basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency, we analysed a sample from a Portugese boy with a family history of favism. Although the biochemical properties of red-cell G6PD from this subject were similar to those of the common variant G6PD Mediterranean, the corresponding mutation (563 C----T) was not present. Instead, polymerase chain reaction (PCR) amplification and sequencing of the entire gene detected a C----T transition at nucleotide 592 in exon VI, changing an arginine residue to a cysteine residue only 10 amino acids downstream from the Mediterranean mutation. Single-strand conformation polymorphism analysis of a PCR-amplified DNA fragment spanning exons VI and VII of the G6PD gene has detected the same mutation, confirmed by sequencing, in a G6PD-deficient patient from Southern Italy. We name this new variant G6PD Coimbra.

This prospective study was performed to quantify glucose-6-phosphate dehydrogenase (G6PD) enzyme activity in deficient males and female heterozygotes. The methods used in the study were the fluorescent spot test, G6PD enzyme electrophoresis on cellulose acetate and quantitative assays. Forty-seven children who had been detected as spot screen deficient at birth were rescreened. Their first degree relatives were also included in the study. The mean enzyme activity of deficient males was 0.74 iu/g Hb (s.d. +/- 0.8), of female heterozygotes was 6.5 iu/g Hb (s.d. +/- 3.2) and of normal males was 12.1 iu/g Hb (s.d. +/- 3.5). The mean activity in deficient males was 6.1% of normal males. Most (35 of 47) of these fell into class 2 in Beutler's classification of G6PD variants. This indicates a population which may be susceptible to favism. Female heterozygotes had an intermediate enzyme activity with a wide scatter. Using a cut off point of enzyme activity of below 9.0 iu/g Hb gave sensitivity and specificity of 87% and 84% in detecting female heterozygotes. This group could be defined more accurately by combining quantitative assays with family studies.

Four cases of fawism are presented. The disease was seen in one male patient, one homozygote and in 3 carriers of G6PD deficit. Diagnostic procedures, course of the haemolytic crisis in these patients, and possibility of prophylaxis in the families with fawism are discussed.

Pityriasis rotunda is a rare dermatosis characterized by circular, dusty scaling, dyschromic patches, quite asymptomatic and mostly described in Japanese and blacks. The authors have seen three cases of pityriasis rotunda in a Sardinian family that are to be added to two other similar reports. The patients were all in good health. An interesting feature was the association with favism. On inquiry it was discovered that many more members of the family were affected by either or both pathologies. The authors believe this condition to be a form of minor acquired ichthyosis of which Sardinia could be an ethnic center.

During a routine screening for G6PD deficiency in the Province of Matera (Southern Italy), an eleven-year-old boy was brought to our attention who had fever obviously caused by a viral infection, but who also had hepatosplenomegaly and haemoglobinuria. The boy had previously experienced two severe haemolytic attacks. At the age of six months severe haemolysis occurred after the ingestion of cooked fava beans. At the age of seven years, the haemolytic episode was very likely triggered by oral administration of co-trimoxazole. The G6PD activity level in erythrocyte lysate was clearly defective (25% of normal). The electrophoretic mobility of G6PD was 110% of normal. These data together with those obtained from biochemical and molecular characterisation allowed the variant to be identified as G6PD A(-). This is the first report of an association between the African type G6PD deficiency variant and favism.

Glucose-6-phosphate dehydrogenase deficiency was demonstrated in a case of favism. The X-linked enzyme defect was expressed in erythrocytes but not in hair root cells. Predictably, the mother shown to be a heterozygous carrier on the basis of intermediate erythrocyte glucose-6-phosphate dehydrogenase activity could not be identified as a carrier by means of hair root study. It seems to be necessary to test the hair roots of at least one enzyme-deficient member of the family to exclude false negative results, if hair root analysis is used for carrier detection. Because of the more or less clonal origin of hair roots, they remain a convenient biopsy material with which to study heterozygosity in X-linked inborn errors of metabolism.

Glucose-6-phosphate dehydrogenase (G6PD); EC 1.1.1.49 from thirty-six unrelated Spanish males was partially purified from blood, and the variants were characterized biochemically and electrophoretically according to the methods recommended by the world Health Organization. Subjects were from multiple geographic regions within Spain, and all suffered from hemolytic anemia, either acute (34 cases) or chronic nonspherocytic (2 cases). Almost all the variants studied presented residual erythrocyte G6PD activity ranging from 0 to 10% of normal, and five different mutants were responsible for the deficient phenotype. Three variants were similar to others previously described: G6PD Mediterranean (11 cases), G6PD Athens-like (3 cases), and G6PD Union (2 cases). The remaining variants were different from the numerous variants already reported and have been considered as new mutants. Provisionally they are called G6PD Betica (19 cases) and G6PD Menorca (1 case). The present study constitutes the first attempt to characterize the deficient G6PD variants found in Spain and supplies new data on the relationship between molecular characteristics of deficient variants and their clinical manifestations. The most important findings can be summarized as follows: (1) The Spanish population is characterized by an important heterogeneity in G6PD deficiency. (2) Although G6PD Mediterranean is very frequent, it presents a relatively high degree of polymorphism. (3) Favism has been observed associated with all kinds of variants described here. (4) G6PD Betica, which is the most frequent variant found in subjects of Southern Spanish origin, has been observed associated with favism in all cases except one.