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1.
BMC Infect Dis ; 20(1): 487, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646433

RESUMO

BACKGROUND: Genetic diversity of ABO blood, glucose-6-phosphate dehydrogenase (G6PD) deficiency and haemoglobin type and their ability to protect against malaria vary geographically, ethnically and racially. No study has been carried out in populations resident in malaria regions in western Kenya. METHOD: A total of 574 malaria cases (severe malaria anaemia, SMA = 137 and non-SMA = 437) seeking treatment at Vihiga County and Referral Hospital in western Kenya, were enrolled and screened for ABO blood group, G6PD deficiency and haemoglobin genotyped in a hospital-based cross-sectional study. RESULT: When compared to blood group O, blood groups A, AB and B were not associated with SMA (P = 0.380, P = 0.183 and P = 0.464, respectively). Further regression analysis revealed that the carriage of the intermediate status of G6PD was associated with risk to SMA (OR = 1.52, 95%CI = 1.029-2.266, P = 0.035). There was, however, no association between AS and SS with severe malaria anaemia. Co-occurrence of both haemoglobin type and G6PD i.e. the AA/intermediate was associated with risk to SMA (OR = 1.536, 95%CI = 1.007-2.343, P = 0.046) while the carriage of the AS/normal G6PD was associated with protection against SMA (OR = 0.337, 95%CI = 0.156-0.915, P = 0.031). CONCLUSION: Results demonstrate that blood group genotypes do not have influence on malaria disease outcome in this region. Children in Vihiga with blood group O have some protection against malaria. However, the intermediate status of G6PD is associated with risk of SMA. Further, co-inheritance of sickle cell and G6PD status are important predictors of malaria disease outcome. This implies combinatorial gene function in influencing disease outcome.


Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Genótipo , Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/sangue , Hemoglobinas/genética , Malária Falciparum/sangue , Malária Falciparum/epidemiologia , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Quênia/epidemiologia , Malária Falciparum/parasitologia , Masculino , Fenótipo , Plasmodium falciparum/isolamento & purificação , Polimorfismo Genético , Risco , Traço Falciforme/genética
2.
Ann Biol Clin (Paris) ; 78(4): 411-416, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32576539

RESUMO

BACKGROUND AND OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy worldwide associated with hemolysis as well as neonatal jaundice, kernicterus, and even death. The goal of this study is to determinate the prevalence of G6PD deficiency in icteric neonates and to investigate its biochemical, hematological and molecular characteristics. PATIENTS AND METHODS: This cross sectional study was carried out on 154 icteric newborns admitted to the Bechir Hamza Children's Hospital in Tunisia. Laboratory evaluations included complete blood count, total serum bilirubin level (TSB), and erythrocyte G6PD activity. The G6PD activity was determined using a quantitative assay, which allowed us to divide the total population into two groups: normal and deficient population. The common G6PD Tunisian mutations (GdA - and GdMed) were determined using the amplification refractory mutation system (ARMS-PCR) method. RESULTS: The prevalence of G6PD deficiency among total population (154 icteric newborns) was 18.83%. Male neonates showed a higher incidence of G6PD deficiency of 11.03% compared to females (7.79%). There was no statistical difference between the two groups (normal and deficient), in relation to the sex, peak TSB level, age at peak TSB, hemoglobin level, and hematocrit. However, there was a significant difference in gestational age. In the deficient group, 48.28% neonates presented the peak TSB level between 3 to 7 days and 55% of the cases show a peak TSB level greater than 250 µmol/L. The G6PD G202A variant was found in 41.37% of cases. CONCLUSION: This study shows a higher prevalence of G6PD deficiency in icteric newborns of Tunisia (18.83%). This emphasizes the necessity of neonatal screening for G6PD deficiency to prevent the exposure of these newborns to known hemolytic agents and, subsequently, to prevent kernicterus or other serious complications.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Icterícia Neonatal/epidemiologia , Análise Química do Sangue , Estudos Transversais , Análise Mutacional de DNA , Feminino , Idade Gestacional , Glucosefosfato Desidrogenase/análise , Glucosefosfato Desidrogenase/sangue , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/genética , Testes Hematológicos , Humanos , Recém-Nascido , Icterícia Neonatal/sangue , Icterícia Neonatal/complicações , Icterícia Neonatal/genética , Masculino , Prevalência , Tunísia/epidemiologia
3.
PLoS One ; 15(3): e0229574, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176714

RESUMO

Cabo Verde aims to eliminate malaria by 2020. In the country, Plasmodium falciparum had been the main parasite responsible for indigenous cases and primaquine is the first line treatment of cases and for radical cure. However, the lack of knowledge of the national prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency may be one of the constraints to the malaria elimination process. Hence, this first study determines the prevalence of G6PD deficiency (G6PDd) in the archipelago. Blood samples were collected from patients who voluntarily agreed to participate in the study, in the health facilities of eight municipalities on four islands, tested with G6PD CareStart ™ deficiency Rapid Diagnosis Test (RDT). All subjects found to be G6PDd by RDT then underwent enzyme quantification by spectrophotometry. Descriptive statistics and inferences were done using SPSS 22.0 software. A total of 5.062 blood samples were collected, in majority from female patients (78.0%) and in Praia (35.6%). The RDT revealed the prevalence of G6PD deficiency in 2.5% (125/5062) of the general population, being higher in males (5.6%) than in females (1,6%). The highest G6PDd prevalence was recorded in São Filipe, Fogo, (5.4%), while in Boavista no case was detected. The G6PDd activity quantification shown a higher number of partially deficient and deficient males (respectively n = 26 and n = 22) compared to females (respectively n = 18 and n = 7), but more normal females (n = 35) than males (n = 11). According to the WHO classification, most of the G6PDd cases belongs to the class V (34.5%), while the Classes II and I were the less represented with respectively 5.8% and zero cases. This study in Cabo Verde determined the G6PDd prevalence in the population, relatively low compared to other African countries. Further studies are needed to characterize and genotyping the G6PD variants in the country.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Malária/epidemiologia , Adolescente , Adulto , Idoso , Cabo Verde/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Glucosefosfato Desidrogenase/sangue , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/enzimologia , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Lactente , Recém-Nascido , Malária/prevenção & controle , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
4.
Am J Trop Med Hyg ; 102(4): 851-856, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32043453

RESUMO

In tropical areas of developing countries, the interactions among parasitic diseases such as soil-transmitted helminths (STHs) and malaria, and glucose-6-phosphate dehydrogenase deficiency (G6PDd), are complex. Here, we investigated their interactions and impact on anemia in school students residing in a conflict zone of northeast Myanmar. A cross-sectional survey was conducted between July and December 2015 in two schools located along the China-Myanmar border. Stool samples from the schoolchildren were analyzed for STH infections, whereas finger-prick blood samples were analyzed for G6PDd, hemoglobin concentrations, and Plasmodium infections. Among 988 enrolled children, Plasmodium vivax, Plasmodium falciparum, hookworm, Ascaris lumbricoides, and Trichuris trichiura infections occurred in 3.3%, 0.8%, 31.5%, 1.2%, and 0.3%, respectively. Glucose-6-phosphate dehydrogenase deficiency was present in 16.9% of the children, and there was a very high prevalence of anemia (73%). Anthropometric measures performed on all children showed that 50% of the children were stunted and 25% wasted. Moderate to severe anemia was associated with STH infections, stunting, and wasting. In addition, children had increasing odds of anemia with increasing burden of infections. This study revealed a high prevalence of G6PDd, STHs, and anemia in schools located in a conflict zone. In areas where malnutrition and STH infections are rampant, testing for both glucose-6-phosphate dehydrogenase and anemia should be considered before treating vivax malaria with 8-aminoquinolines.


Assuntos
Anemia/epidemiologia , Conflitos Armados , Deficiência de Glucosefosfato Desidrogenase/genética , Helmintíase/epidemiologia , Malária/sangue , Solo/parasitologia , Adolescente , Criança , Feminino , Helmintíase/sangue , Helmintíase/parasitologia , Humanos , Malária/epidemiologia , Malária/parasitologia , Masculino , Mianmar/epidemiologia
5.
Am J Trop Med Hyg ; 102(1): 156-158, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31701865

RESUMO

We herein report the first case of Mediterranean glucose-6-phosphate dehydrogenase (G6PD) variant from Bangladesh. A boy had been admitted to hospital and was diagnosed with uncomplicated Plasmodium vivax infection and treated with 30 mg/kg body weight (BW) chloroquine for 3 days and 4.8 mg/kg BW primaquine (PQ) to be taken over 14 days. The boy was discharged but represented 4 days later with severe hemoglobinuria and fatigue. Hemoglobin was measured at 6.0 g/dL and serum bilirubin was at 5.6 mg/dL, although malaria microscopy was negative. The boy had taken the 4-fold recommended daily dose of PQ and was treated with two fresh blood transfusions. Subsequent molecular analysis showed the boy to have the Mediterranean G6PD variant and a G6PD activity of 0.93 U/gHb.


Assuntos
Cloroquina/uso terapêutico , Deficiência de Glucosefosfato Desidrogenase , Hemoglobinúria/induzido quimicamente , Malária/tratamento farmacológico , Primaquina/efeitos adversos , Primaquina/uso terapêutico , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Transfusão de Sangue , Criança , Cloroquina/administração & dosagem , Deficiência de Glucosefosfato Desidrogenase/genética , Hemoglobinúria/terapia , Humanos , Masculino
6.
J Hum Genet ; 65(3): 263-270, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31863082

RESUMO

G6PD deficiency is the commonest enzyme deficiency found in humans. Current diagnostic methods lack sensitivity to detect all cases of G6PD deficiency. We evaluated the reverse dot blot flow-through hybridisation assay designed to detect simultaneously multiple known G6PD mutations in a group of Malaysian neonates. Archival DNA samples from 141 G6PD-deficient neonates were subjected to reverse dot blot flow-through hybridisation assay using the GenoArray Diagnostic Kit (Hybribio Limited, Hong Kong) and DNA sequencing. The method involved PCR amplification of 5 G6PD exons using biotinylated primers, hybridisation of amplicons to a membrane containing oligoprobes designed for G6PD mutations known to occur in the Malaysian population and colour detection by enzyme immunoassay. The assay detected 13 of the 14 G6PD mutations and genotyped 133 (94.3%) out of 141 (102 males, 39 females) cases. Among the 39 female G6PD-deficient neonates, there were 7 homozygous and 6 compound heterozygous cases. The commonest alleles were G6PD Viangchan 871G > A (21%) and G6PD Mahidol 487G > A(20%) followed by G6PD Mediterranean 563C > T, (14%), G6PD Vanua Lava 383T > C (12%), G6PD Canton 1376G > T (10%), G6PD Orissa 131C > G (6.3%) G6PD Coimbra 592C > T (5.6%) plus 6 other mutations. DNA sequencing of remaining cases revealed 6 cases of intron 11 nt 93C > T not previously reported in Malaysia and two novel mutations, one case each of nt 1361G > T and nt 1030G > A. We found the reverse dot blot assay easy to perform, rapid, accurate and reproducible, potentially becoming an improved diagnostic test for G6PD deficiency.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Mutação/genética , Éxons/genética , Feminino , Genótipo , Deficiência de Glucosefosfato Desidrogenase/patologia , Humanos , Recém-Nascido , Íntrons/genética , Malásia/epidemiologia , Masculino , Reação em Cadeia da Polimerase
7.
Redox Biol ; 28: 101363, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31707353

RESUMO

Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway that modulates cellular redox homeostasis via the regeneration of NADPH. G6PD-deficient cells have a reduced ability to induce the innate immune response, thus increasing host susceptibility to pathogen infections. An important part of the immune response is the activation of the inflammasome. G6PD-deficient peripheral blood mononuclear cells (PBMCs) from patients and human monocytic (THP-1) cells were used as models to investigate whether G6PD modulates inflammasome activation. A decreased expression of IL-1ß was observed in both G6PD-deficient PBMCs and PMA-primed G6PD-knockdown (G6PD-kd) THP-1 cells upon lipopolysaccharide (LPS)/adenosine triphosphate (ATP) or LPS/nigericin stimulation. The pro-IL-1ß expression of THP-1 cells was decreased by G6PD knockdown at the transcriptional and translational levels in an investigation of the expression of the inflammasome subunits. The phosphorylation of p38 MAPK and downstream c-Fos expression were decreased upon G6PD knockdown, accompanied by decreased AP-1 translocation into the nucleus. Impaired inflammasome activation in G6PD-kd THP-1 cells was mediated by a decrease in the production of reactive oxygen species (ROS) by NOX signaling, while treatment with hydrogen peroxide (H2O2) enhanced inflammasome activation in G6PD-kd THP-1 cells. G6PD knockdown decreased Staphylococcus aureus and Escherichia coli clearance in G6PD-kd THP-1 cells and G6PD-deficient PBMCs following inflammasome activation. These findings support the notion that enhanced pathogen susceptibility in G6PD deficiency is, in part, due to an altered redox signaling, which adversely affects inflammasome activation and the bactericidal response.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/imunologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , NADPH Oxidases/metabolismo , Fator de Transcrição AP-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Técnicas de Silenciamento de Genes , Deficiência de Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/microbiologia , Células HEK293 , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Lipopolissacarídeos/efeitos adversos , Masculino , Células THP-1/efeitos dos fármacos , Células THP-1/imunologia , Células THP-1/microbiologia , Adulto Jovem
8.
Redox Biol ; 28: 101332, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581069

RESUMO

Mice deficient in glucose-6-phosphate dehydrogenase (G6PD) cannot replenish the cellular antioxidant glutathione, which detoxifies neurodegenerative reactive oxygen species (ROS). To determine the functional consequences of G6PD deficiency, young and aging G6PD-deficient mice were evaluated for brain G6PD activity, DNA damage (comets, γH2AX), Purkinje cell loss, brain function (electrophysiology, behaviour) and lifespan. DNA comet formation was increased and Purkinje cell counts were decreased in a G6pd gene dose-dependent fashion. γH2AX formation varied by age, sex and brain region, with increased levels in G6PD-deficient young and aging females, and in aging males. Aging male G6PD-deficient mice exhibited synaptic dysfunction in hippocampal slices. G6PD-deficient young and aging females exhibited deficits in executive function, and young deficient mice exhibited deficits in social dominance. Conversely, median lifespan in G6PD-deficient females and males was enhanced. Enhanced ROS-initiated brain damage in G6PD deficiency has functional consequences, suggesting that G6PD protects against ROS-mediated neurodegenerative disorders.


Assuntos
Dano ao DNA , Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Transtornos Mentais/etiologia , Transtornos Mentais/metabolismo , Animais , Encéfalo/metabolismo , Quebras de DNA de Cadeia Dupla , Quebras de DNA de Cadeia Simples , Modelos Animais de Doenças , Ativação Enzimática , Feminino , Masculino , Camundongos , Oxirredução , Células de Purkinje/metabolismo
9.
Malar J ; 18(1): 340, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590661

RESUMO

BACKGROUND: G6PD enzyme deficiency is a common enzymatic X-linked disorder. Deficiency of the G6PD enzyme can cause free radical-mediated oxidative damage to red blood cells, leading to premature haemolysis. Treatment of Plasmodium vivax malaria with primaquine poses a potential risk of mild to severe acute haemolytic anaemia in G6PD deficient people. In this study, the prevalence and distribution of G6PD mutations were investigated across broad areas of Ethiopia, and tested the association between G6PD genotype and phenotype with the goal to provide additional information relevant to the use of primaquine in malaria treatment. METHODS: This study examined G6PD mutations in exons 3-11 for 344 febrile patient samples collected from seven sites across Ethiopia. In addition, the G6PD enzyme level of 400 febrile patient samples from Southwestern Ethiopia was determined by the CareStart™ biosensor. The association between G6PD phenotype and genotype was examined by Fisher exact test on a subset of 184 samples. RESULTS: Mutations were observed at three positions of the G6PD gene. The most common G6PD mutation across all sites was A376G, which was detected in 21 of 344 (6.1%) febrile patients. Thirteen of them were homozygous and eight were heterozygous for this mutation. The G267+119C/T mutation was found in 4 (1.2%) individuals in South Ethiopia, but absent in other sites. The G1116A mutation was also found in 4 (1.2%) individuals from East and South Ethiopia. For the 400 samples in the south, 17 (4.25%) were shown to be G6PD-deficient. G6PD enzyme level was not significantly different by age or gender. Among a subset of 202 febrile patients who were diagnosed with malaria, 11 (5.45%) were G6PD-deficient. These 11 infected samples were diagnosed with Plasmodium vivax by microscopy. Parasitaemia was not significantly different between the G6PD-deficient and G6PD-normal infections. CONCLUSIONS: The prevalence of G6PD deficiency is modest among febrile patients in Ethiopia. G6PD deficiency testing is thus recommended before administrating primaquine for radical cure of P. vivax infected patients. The present study did not indicate a significant association between G6PD gene mutations and enzyme levels.


Assuntos
Antimaláricos/uso terapêutico , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Malária Vivax/prevenção & controle , Primaquina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimaláricos/efeitos adversos , Criança , Pré-Escolar , Etiópia/epidemiologia , Feminino , Genótipo , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Primaquina/efeitos adversos , Adulto Jovem
10.
PLoS One ; 14(9): e0220977, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31525211

RESUMO

BACKGROUND: Primaquine is recommended by the World Health Organization (WHO) for radical treatment of Plasmodium vivax malaria. This drug is known to provoke acute hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Due to lack of data on G6PD deficiency, the use of primaquine has been limited in Africa. In the present study, G6PD deficiency was investigated in blood donors of various ethnic groups living in Nouakchott, a P. vivax endemic area in Mauritania. METHODOLOGY/PRINCIPAL FINDINGS: Venous blood samples from 443 healthy blood donors recruited at the National Transfusion Center in Nouakchott were screened for G6PD activity using the CareStart G6PD deficiency rapid diagnostic test. G6PD allelic variants were investigated using DiaPlexC G6PD genotyping kit that detects African (A-) and Mediterranean (B-) variants. Overall, 50 of 443 (11.3%) individuals (49 [11.8%] men and 1 [3.7%] woman) were phenotypically deficient. Amongst men, Black Africans had the highest prevalence of G6PD deficiency (15 of 100 [15%]) and White Moors the lowest (10 of 168, [5.9%]). The most commonly observed G6PD allelic variants among 44 tested G6PD-deficient men were the African variant A- (202A/376G) in 14 (31.8%), the Mediterranean variant B- (563T) in 13 (29.5%), and the Betica-Selma A- (376G/968C) allelic variant in 6 (13.6%). The Santamaria A- variant (376G/542T) and A variant (376G) were observed in only one and two individuals, respectively. None of the expected variants was observed in 8 (18.2%) of the tested phenotypically G6PD-deficient men. CONCLUSION: This is the first published data on G6PD deficiency in Mauritanians. The prevalence of phenotypic G6PD deficiency was relatively high (11.3%). It was mostly associated with either African or Mediterranean variants, in agreement with diverse Arab and Black African origins of the Mauritanian population.


Assuntos
Variação Genética , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Malária Vivax/complicações , Malária Vivax/diagnóstico , Plasmodium vivax , Alelos , Testes Diagnósticos de Rotina , Feminino , Genótipo , Humanos , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Masculino , Mauritânia/epidemiologia , Mauritânia/etnologia , Fenótipo
11.
Gene ; 715: 144027, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31374327

RESUMO

OBJECTIVES: To explore the clinical and molecular characteristics of a Chinese Zhuang minority patient with leukocyte adhesion deficiency type-1 (LAD-1) and glucose-6-phosphate dehydrogenase deficiency (G6PDD). METHODS: Routine clinical and physical examinations were performed, and patient data was collected and analyzed. Protein expression levels of Itgb2 and glucose-6-phosphate dehydrogenase (G6pd) proteins were assessed by flow cytometry and the glucose-6-phosphate (G6P) substrate method, respectively. Whole exome sequencing was performed to investigate genetic variations of the patient and his parents. RESULTS: The patient had fester disease and delayed separation of the umbilical cord at birth. Staphylococcus was detected in the fluid secretion of the auditory meatus of the patient. He exhibited a recurrent cheek scab, swollen hand, and swollen gum. Hematological examination indicated dramatic elevation of leukocytes including lymphocytes, monocytes, neutrophils and eosinophils. A novel homozygous mutation was detected in the ITGB2 gene of the patient, which was determined to be a two nucleotide deletion at the site of c.1537-1538 (c.1537-1538delGT), causing a frameshift of 24 amino acids from p.513 and inducing a stop codon (p.V513Lfs*24). A base substitution mutation was identified at c.1466 (c.1466G>T) of G6PD on chromosome X of the patient, which resulted in an amino acid change from arginine to leucine at p.489 (p.R489L). The patient also showed deficient lymphocyte expression of CD18 (2.99%) and significant downregulation of the G6pd protein. CONCLUSIONS: The patient was diagnosed with G6PDD and moderate LAD-1. The combination of LAD-1 and G6PDD in this case may have been due to the high incidence of genetic disease in this minority ethnic population. Analyzing existing LAD-1 and G6PDD cases from different populations can facilitate disease diagnosis and treatment. Particularly, reporting pathogenic mutations of LAD-1 and G6PDD will be crucial for genetic testing and prenatal diagnosis in an effort to decrease the incidence of these diseases.


Assuntos
Antígenos CD18/genética , Deficiência de Glucosefosfato Desidrogenase/genética , Homozigoto , Síndrome da Aderência Leucocítica Deficitária/genética , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Grupo com Ancestrais do Continente Asiático , Antígenos CD18/metabolismo , Deficiência de Glucosefosfato Desidrogenase/patologia , Humanos , Lactente , Síndrome da Aderência Leucocítica Deficitária/metabolismo , Síndrome da Aderência Leucocítica Deficitária/patologia , Leucócitos/metabolismo , Leucócitos/patologia , Masculino
12.
Arch Pediatr ; 26(6): 370-373, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278024

RESUMO

We report the case of a neonate with a new, previously undescribed, glucose-6-phosphate dehydrogenase (G6PD) gene mutation, which was revealed by severe cholestasis, hyperbilirubinemia, and transient liver dysfunction. The severity of the clinical phenotype with ongoing chronic hemolytic anemia suggests that this mutation belongs to class 1 G6PD deficiency. The hemizygous mutation «c.675G>c; p.Trp225Cys¼ was detected by genomic sequencing. Since severe G6PD deficiency can be revealed by cholestasis, it is important to check G6PD enzyme activity when faced with a case of liver dysfunction in the neonatal period.


Assuntos
Colestase/etiologia , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glucosefosfato Desidrogenase/genética , Insuficiência Hepática/etiologia , Mutação , Colestase/diagnóstico , Marcadores Genéticos , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/genética , Insuficiência Hepática/diagnóstico , Humanos , Recém-Nascido , Masculino
15.
Niger Postgrad Med J ; 26(2): 118-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31187752

RESUMO

Background: Sickle cell disease (SCD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency are inherited disorders associated with chronic haemolysis. Therefore, coinheritance of both disorders could worsen haemolysis in the former and compound a haemolytic crisis. This study compared clinical and laboratory features of deficient and non-deficient SCD patients and the G6PD activities of SCD patients and apparently healthy controls. Materials and Methods: This is a case-control study of 175 SCD patients and 166 non-SCD controls. G6PD assay was carried out on haemolysate from washed red cells. The G6PD activity was measured by spectrophotometry. Results: The mean age of patients and controls was 27.3 ± 9.4 and 35.9 ± 9.7 years, respectively, with 75 (46.2%) and 87 (52.4%) being males, respectively. G6PD activity was similar in cases and controls (6.7 ± 3.3 vs. 6.9 ± 3.0 IU/gHb), respectively (P = 0.6). The prevalence of G6PD deficiency was higher in patients than controls (28.6% vs. 22.3%, P = 0.18), and SCD patients were twice more likely to have enzyme activities below 3.0 IU/gHb. No significant difference was observed in the clinical parameters between deficient and non-deficient patients. Deficient patients were more likely to have lower haematocrit (22.8 ± 3.9% vs. 24.5 ± 5%, P = 0.04) and non-significantly higher bilirubin and reticulocyte counts. Furthermore, in patients, severe deficiency resulted in higher bilirubin than in those with mild deficiency (60.5 vs. 21.7 IU/L, P < 0.001). G6PD activity correlated positively with haematocrit (r = 0.91, P = 0.01) and mean corpuscular haemoglobin concentration (r = 0.17, P = 0.02). Conclusions: Coinheritance of both disorders could worsen haemolysis in SCD patients, and care should, therefore, be taken in the choice of drugs in deficient SCD patients.


Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/genética , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Hemólise/genética , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/epidemiologia , Bilirrubina/sangue , Estudos de Casos e Controles , Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Hemoglobinas/análise , Humanos , Masculino , Nigéria/epidemiologia , Prevalência , Adulto Jovem
16.
Pediatr Blood Cancer ; 66(8): e27807, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31094093

RESUMO

BACKGROUND: The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV-exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa. METHODS: A 3-year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high-burden districts, (2) document the prevalence among HIV-exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co-inheritance of known genetic modifiers of sickle cell disease. RESULTS: A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid-Northern districts, in both HIV-exposed and nonexposed children. Based on crude birth-rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40-0.64, P < .0001). Alpha-thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution. CONCLUSIONS: High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district-level comprehensive care programs.


Assuntos
Anemia Falciforme/diagnóstico , Genes Modificadores , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Infecções por HIV/diagnóstico , Programas de Rastreamento/métodos , Talassemia alfa/diagnóstico , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Pré-Escolar , Comorbidade , Feminino , Seguimentos , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/genética , HIV/genética , HIV/isolamento & purificação , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Prognóstico , Estudos Prospectivos , Talassemia alfa/complicações , Talassemia alfa/epidemiologia , Talassemia alfa/genética
17.
Gene ; 707: 143-150, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31075411

RESUMO

OBJECTIVE: Present study was undertaken to study the association between sickle cell anemia (SCA) and glucose-6-phosphate dehydrogenase (G6PD) deficiency from Sahu and Kurmi population of Durg and Rajnandgaon district of Chhattisgarh, India. METHOD: A random sampling of 1749 individuals was done. SCA and G6PD deficiency was detected by slide test followed by electrophoresis and Enzymatic reaction indicated by change in colour respectively. Further the samples were subjected to analyze glutathione-S-transferase (GST) i.e. GSTM1 and GSTT1 gene polymorphism, variance of G6PD among G6PD deficient samples by PCR-RFLP. Oxidative stress and DNA damage by comet assay was also analyzed. RESULTS: Present finding indicates positive correlation between SCA and G6PD deficiency in Durg and Rajnandgaon district [Durg: (r = 0.92; HbAS-G6PDd and r = 0.56; HbSS-G6PDd) Rajnandgaon: (r = 0.63; HbAS-G6PDd and r = 0.86; HbSS-G6PDd)]. Significant changes (P < 0.05) in antioxidant enzymatic parameters were observed in HbSS and G6PD with sickle positive individual. Assessment of DNA damage by Comet assay considering Head DNA percent, Tail DNA percent, Tail length and Tail moment also showed significant changes (P < 0.05) within all concerned parameters in HbSS and G6PD with sickle positive individual. Analysis of GST gene polymorphism showed that frequency of individuals carrying the GSTM1 null genotype was higher in HbAS (60%) and the frequency of individual carrying the GSTT1 null genotype was found higher in HbSS (66.6%). G6PD variants analysis also confirmed the presence of highest percentage of mutation among G6PD deficient population as compared to control and a positive correlation was observed between G6PD deficiency and mutant variants of G6PD gene [Rajnandgaon: (r = 0.67; G6PDd-Mahidol mutated and r = 0.90; G6PDd-Union mutated) Durg: (r = 0.91; G6PDd-Mahidol mutated and r = 0.01; G6PDd-Union mutated)] . CONCLUSION: Thus present finding indicates positive correlation between SCA and G6PD deficiency in Chhattisgarh, India.


Assuntos
Anemia Falciforme/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Glucosefosfato Desidrogenase/genética , Glutationa Transferase/genética , Anemia Falciforme/genética , Dano ao DNA , Feminino , Genótipo , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Índia/epidemiologia , Masculino , Mutação , Estresse Oxidativo , Polimorfismo de Fragmento de Restrição , Traço Falciforme/epidemiologia , Traço Falciforme/genética
18.
Clin Chim Acta ; 495: 271-277, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31022393

RESUMO

BACKGROUND: Patients with glucose-6-phosphate dehydrogenase deficiency might develop acute hemolytic anemia, chronic hemolytic anemia, and neonatal hyperbilirubinemia when exposed to high levels of oxidative stress. Severe hemolysis may occur in not only patients but also female carriers under certain conditions. However, 80%-85% of female carriers were undetected in an existing newborn screening program because of their wide-ranging levels of enzyme activity. METHODS: We developed a cost- and time-efficient multiplex SNaPshot assay using dried blood spots. RESULTS: By detecting 21 common mutations in Taiwan and Southeast Asia, the assay could determine 98.2% of the mutant alleles in our cohort of Taiwanese newborns. The 9 undetermined mutant alleles were consequently detected by Sanger sequencing, of which 5 unpublished variations-c.187G > A (Pingtung), c.585G > C (Tainan), c.586A > T (Changhua), c.743G > A (Chiayi), and c.1330G > A (Tainan-2)-were detected. Furthermore, 13% of mild mutations were missed in male infants whose enzyme levels at 6.1-7.0 U/gHb in the newborn screening program when set the cutoff value at 6.0 U/gHb. We therefore suggest increasing the cutoff value and applying the multiplex SNaPshot assay as the second tier for neonatal screening. CONCLUSIONS: Our approach could significantly increase the detection rate of male patients and female carriers with a reasonable cost and a reasonable number of clinic referrals.


Assuntos
Primers do DNA/genética , Teste em Amostras de Sangue Seco/métodos , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Triagem Neonatal/métodos , Sequência de Bases , Estudos de Coortes , Feminino , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Recém-Nascido , Masculino , Risco , Análise de Sequência de DNA , Fatores de Tempo
19.
Atherosclerosis ; 282: 148-153, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30731288

RESUMO

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is associated with high morbidity and mortality. Studies in animal models and humans suggested that glucose‒6‒phosphate dehydrogenase (G6PD) deficiency, a genetically inherited condition causing haemolytic anemia, may be a risk factor for CVD. This hypothesis was tested in a large cohort from Northern Sardinia, where the population prevalence of G6PD deficiency is the highest in the Mediterranean area. METHODS: A retrospective observational case‒control study was performed using clinical records of 9604 patients undergoing digestive endoscopy between 2002 and 2017, with a known G6PD status and a complete clinical history including CVD and leading CVD risk factors. To circumvent covariates imbalance between cases and controls, a 1:2 propensity score‒matched analysis was performed. RESULTS: Major predictors of CVD, as expected, were age (OR 1.07; 95%CI 1.06-1.08), male sex (1.63; 95%CI 1.29-2.06), high blood pressure (OR 1.46; 95%CI 1.16-1.84), smoking (OR 3.03; 95%CI 2.42-3.79), diabetes (OR 1.65; 95%CI 1.23-2.21) and hypercholesterolemia (OR 2.20; 95%CI 1.71-2.84). The propensity score matching procedure resulted in 1123 G6PD deficient patients and 2246 patients with normal enzyme activity. When G6PD status was regressed on the CVD, including propensity score as a continuous covariate, an OR of 1.71 (95%CI 1.17-2.49; p = 0.006) was obtained. CONCLUSIONS: G6PD deficiency is significantly associated with increased risk of CVD, although the underlying mechanisms are still poorly understood. The loss of important protective pathways against oxidative stress, especially in the early stages of atherogenesis, might play a crucial role.


Assuntos
Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Glucose-6-Fosfatase/genética , Deficiência de Glucosefosfato Desidrogenase/complicações , Adulto , Idoso , Anemia Hemolítica/complicações , Anemia Hemolítica/genética , Antioxidantes/metabolismo , Aterosclerose , Doenças Cardiovasculares/enzimologia , Estudos de Casos e Controles , Progressão da Doença , Endoscopia , Feminino , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco
20.
J Neonatal Perinatal Med ; 12(2): 203-207, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30741698

RESUMO

Glucose-6-phosphate dehydrogenase deficiency (D-G6PD) is a common erythroenzymopathy that needs to be addressed as an important public health issue. Proper population monitoring is needed to anticipate clinical complications. A joint venture between Genomi-k (a Mexican company focused on newborn screening) and several university researchers conducted a retrospetive study for D-G6PD based on 156,152 newborn screening reports belonging to the Mexican population comprising a period of 10 years. We identified 540 male newborns affected with this deficiency, representing an incidence of 6.78 cases per 1,000 newborn males. A single double mutation of G202A:A376G was detected in 97.22% of cases. In regions where there is an absence of a national centralized health data for D-G6PD, information from a non-probabilistic large population sample can be used as a national incidence subrogate.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Incidência , Recém-Nascido , Masculino , México/epidemiologia , Mutação , Triagem Neonatal , Estudos Retrospectivos
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