Deficiencia de glucosa-6-fosfato deshidrogenasa en recién nacidos en Argentina / Glucose-6-phosphate dehydrogenase deficiency in newborns in Argentina / Deficiência de glicose-6-fosfato desidrogenase em recém-nascidos na Argentina

En Argentina la pesquisa neonatal es obligatoria por ley para ciertas condiciones, pero no para la deficiencia de Glucosa-6-Fosfato Deshidrogenasa (G6PD). La deficiencia de G6PD es un trastorno ligado al cromosoma X que puede causar ictericia neonatal, eventualmente kernicterus y hemólisis intravascular aguda en asociación a la exposición a sustancias oxidantes, la ingestión de ciertos alimentos, drogas o medicamentos, algunas infecciones, o cualquier otra situación que implique estrés celular. Es una de las enzimopatías más frecuentes en todo el mundo. El objetivo de este estudio fue determinar la prevalencia de la deficiencia de G6PD en Argentina. Se analizaron 4.500 muestras de sangre seca en varones recién nacidos provenientes de diferentes regiones del país. La actividad de la enzima se determinó cuantitativamente mediante un método fluorométrico semiautomatizado desarrollado en el laboratorio específico para la medición del NADPH producido. El mismo fue evaluado frente a un método comercial. Se hallaron 13 (0,29%) niños que expresaron deficiencia total y 33 (0,73%) deficiencia parcial. Este hallazgo demuestra que la deficiencia de G6PD es una condición frecuente, la detección es factible y no sólo sería útil para la atención especializada contra hemólisis severa en el neonato, sino también para tomar otras medidas preventivas en la edad adulta.

In Argentina, newborn screening is mandatory by law for certain conditions, but not for Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. G6PD deficiency is an X chromosome-linked disorder which causes, in most cases, neonatal jaundice, and even kernicterus and acute intravascular hemolysis in association with exposure to oxidizing substances, ingestion of certain foods, drugs or medications, some infections, or any other situation involving cellular stress. It is one of the most common enzymopathies in the world. The aim of this study was to determine the prevalence of G6PDH deficiency in Argentina. A total of 4.500 newborn male dried blood samples from different regions of the country were analyzed. The activity of the enzyme was quantitatively determined by an "in house" developed fluorometric method, measuring the rate of formation of NADPH. It was evaluated against a commercial method. A total of 13 (0.29%) children expressing total deficiency were found, while 33 (0.73%) demonstrated intermediate deficiency. This finding is important as such patients must receive a preventive and educational care. Screening for G6PDH deficiency is feasible and not only would it take early preventive measures against severe hemolysis in the neonatal period, but also other preventive measures later in life.

Na Argentina, a pesquisa neonatal é obrigatória por lei para determinadas condições, mas não para a deficiência de glicose-6-fosfato desidrogenase (G6PD). Deficiência de G6PD é um distúrbio ligado ao cromossomo X que pode provocar icterícia neonatal, kernicterus e hemólise intravascular aguda em associação com a exposição a substâncias oxidantes, a ingestão de certos alimentos, drogas ou medicamentos, algumas infecções, ou qualquer outra situação que envolva estresse celular. É uma das enzimopatias mais frequentes em todo o mundo. O objetivo deste estudo foi determinar a prevalência de deficiência de G6PDH na Argentina. Testamos 4.500 amostras de sangue seco de recém-nascidos do sexo masculino originários de diferentes regiões do país. A atividade da enzima foi determinada quantitativamente através de um método fluorimétrico semi-automatizado desenvolvido no laboratório específico para medir o NADPH produzido. O mesmo foi avaliado perante um método comercial. Acharam-se 13 (0,29%) crianças expressando deficiência total, enquanto que 33 (0,73%) demonstraram deficiência parcial. Este achado demonstra que a deficiência de G6PD é uma condição frequente, sua detecção é factível e não só seria útil para o atendimento especializado contra hemólise severa no neonato, mas também para tomar outras medidas preventivas na idade adulta.

Epidemiological, clinical and laboratory profile of glucose-6-phosphate dehydrogenase deficiency in the middle and north of Iraq: a comparative study

This study determined the epidemiological, clinical and laboratory profile of glucose-6-phosphate dehydrogenase [G6PD] deficiency in Baghdad [central Iraq] and compared it with previous data from Mosul [northern Iraq]. We reviewed the records of 156 under-5-year-olds with G6PD deficiency admitted to 3 hospitals in Baghdad over a 6-year period. A preponderance of males was noted in both Baghdad and Mosul [1.6:1 and 3.4:1 respectively]. Family history of G6PD deficiency was positive in 19.2% of patients in Baghdad and 13.6% in Mosul. A majority of patients in Baghdad [69.2%] and Mosul [76.1%] showed haemolysis within 1-3 days of exposure to noxious agents. Similarities in the profiles from Baghdad and Mosul suggest that there are similar G6PD variants and similar exposure to precipitating agents

Glucose-6-phosphate dehydrogenase deficiency as a cause of neonatal jaundice in Zagazig university hospital

Jaundice is a common problem affecting 50% to 70% of term infants and more than 80% of preterms, its mechanism is multifactorial; increased production, impaired conjugation and impaired excretion of bilirubin. Glucose-6-phosphate dehydrogenase [G-6-PD] deficiency the most common red cell enzyme abnormality associated with hemolysis. It is also known to be associated with neonatal jaundice, kernicterus, and even death. Identify neonates suffering pathological unconjugated hyperbilirubinemia particularly due to G-6-PD deficiency in Zagazig University Hospital. Two hundred clinically jaundiced neonates were enrolled in this study. Their mean gestational age was 36.65 +/- 1.76 weeks, mean birth weight was 2.9 +/- 0.49 kg, mean age at time of admission was 6.5 +/- 3.72 days, 121 were males and 79 were females [representing 60.5% and 39.5% respectively]. In addition 60 age and sex matched healthy neonates served as a control group. AII neonates were subjected to history taking, clinical examination, and measurement of total and direct serum bilirubin. Upon plotting total serum bilirubin [TSB] on bilirubin nomogram 123 neonates were identified as having pathological hyperbilirubinemia and the remaining 77 neonates were excluded from the study in addition, 22 neonates were identified as having direct [conjugated] hyperbilirubinemia and were also excluded from the study. The remaining 101 [50.5%] neonates [61 males and 40 females] were diagnosed as having pathological unconjugated hyperbilirubinemia and were subjected to laboratory investigations in the form of; CBC, peripheral blood smear, reticulocytic count, direct Coombs' test, ABO and Rh blood grouping for mothers and neonates, liver function test, urine analysis, sepsis screen [C-reactive protein, total and differential leucocytic count and band cell count], serum TSH and T4, and G-6-PD enzyme assay. Results: Out of 101 neonates wfth pathological unconjugated hyperbilirubinemia G-6-PD deficiency was detected in 13 [12.9%] neonates, 10 of them were males and 3 were females [representing 76.9% and 23.1% respectively]. G-6-PD deficiency is an important cause of neonatal jaundice in both males and females

Intervention and prevention of hereditary hemolytic disorders in India: a case study of two ethnic communities of Sundargarh district in Orissa.

OBJECTIVES: This study was aimed at to sensitize, motivate, and screen two major vulnerable tribal communities--Bhuyan and Kharia, for hemoglobinopathies and allied hemolytic disorders, along with prospective and retrospective genetic/marriage counseling to the affected persons. For sustainability, imparting of relevant training to local paramedical staff, and to undertake periodic follow up for evaluation, intervention and clinical management through local PHCs/hospitals. METHODOLOGY: Tribal people in Orissa live in clusters practicing inter-village marriages following tribal endogamy and clan exogamy. The random sampling procedure for the selection of whole village was followed. Population of each tribe was representative because incoming and outgoing married women represent other surrounding villages belonging to their community. The pre- and post-intervention knowledge, attitude and practice (KAP) studies were conducted. Sensitization, motivation and education for carrier detection were carried out through IEC materials, holding interactive meetings and discussions at district, block and village levels. Standard biochemical and hematological techniques were followed for analysis of blood samples. Relevant training to local health personnel was imparted. Both prospective and retrospective intervention and genetic/marriage counseling was done through local PHC doctor. RESULTS: Study revealed high occurrence of hemoglobinopathies in Bhuyan (9.8%) and Kharia (13.3%) tribes, including uncommon hemoglobin variants like hemoglobin D, E, beta-thalassemia, and hereditary persistence of fetal hemoglobin (HPFH). G-6-PD enzyme deficiency was high in Dhelki Kharia (30.7%) and in Dudh Kharia (19.2%), whereas, it was recorded to be 21.1%, 16.3% and 13.7% in Paraja, Paik and Paudi Bhuyan subtribes, respectively. Use of antimalarials was cautioned in these tribal communities. Due to low frequency of Rhesus (D) negative (0.2-1.2%), the Rhesus (D) incompatibility problem seemed to be absent. Impact of methodical and prudent intervention and preventive strategies was found positive and encouraging. CONCLUSIONS: Adoption of a biomedical anthropological approach for implementing and evolving health seeking cooperative strategy that was tribal-oriented, tribal-friendly and tribal-participatory for intervention and prevention of common hemolytic disorders was found effective. Success of this strategy was apparent with overwhelming response of tribal people towards changing the traditional mindset, improving the health and quality of life. Health must meet the needs and perception of the people.

Efficacy of clofibrate on severe neonatal jaundice associated with glucose-6-phosphate dehydrogenase deficiency (a randomized clinical trial).

Glucose-6-phosphate dehydrogenase (G6PD) deficiency may cause severe hyperbilirubinemia with bilirubin encephalopathy unless intervention is initiated. The aim of this study was to assess the efficacy of clofibrate in full term G6PD deficient neonates with jaundice. A randomized clinical trial study was performed in two groups of full-term G6PD deficient jaundiced neonates (clofibrate treated group, n = 21; control group, n = 19). Infants in the clofibrate group received a single oral dose of 100 mg/kg clofibrate, whereas control group received nothing. Both groups were treated with phototherapy. Serum total and direct bilirubin levels were measured at the onset of treatments, 16, 24 and 48 hours later. On enrollment, the mean total serum bilirubin (TSB) level in the clofibrate treated group was 18.40 +/- 2.41 and in the control group was 17.49 +/- 1.03 (p = 0.401). At 16, 24 and 48 hours of treatment, the mean TSB in the clofibrate group were 15.2 +/- 1.9, 12.6 +/- 2.4, and 10.1 +/- 2.4 and in the control group were 16.5 +/- 1.2, 13.3 +/- 2.2 and 11.4 +/- 2.4, respectively (p = 0.047). At 48 hours, 7 (33%) cases in the clofibrate group and one (5%) case in the control group were discharged with a TSB < 10 mg/dl (p = 0.031). No side effects were observed on serial examinations during hospitalization, or on the 1st and 7th days after discharge. The results show that clofibrate induces a faster decline in serum total bilirubin level, a shorter duration of phototherapy, and hospitalization with no side effects in full-term G6PD deficient neonates with jaundice.

Hematological findings and severity of G6PD deficiency in Vataliya Prajapati subjects.

OBJECTIVES: The present study was undertaken to assess the clinical implication of G6PD deficiency in Vataliya Prajapati (VP) subjects in Surat. METHOD: Blood samples of 954 children and 690 adults were collected in camps. Cord blood samples of 57 neonates born to VP mother were also collected. Medical history and other relevant information of all subjects were obtained. Samples were screened for G6PD deficiency by NBT test and the enzyme activity was estimated by WHO method. Hematological parameters were measured on hematology analyzer while reticulocyte count was measured using new methylene blue dye. RESULTS: The G6PD enzyme deficiency was detected in 27.5% males and 12.8% females. The enzyme levels in deficient subjects suggested class II variant. Hematological studies indicated mild anemia in G6PD deficient persons. Reticulocyte count was slightly raised (p <0.05). Out of eight G6PD deficient neonates one developed mild jaundice. Five deficient male adults gave the history of hemolytic crisis, three of them had typhoid, one tuberculosis and remaining one had fever of unknown origin. CONCLUSION: G6PD deficiency in majority of Vataliya Prajapati subjects is of mild type. However it is essential to test every Vataliya Prajapati subject for G6PD deficiency as certain infections and drugs can cause crisis in deficient person.

G6PD deficiency in Vataliya Prajapati community settled in Surat.

BACKGROUND: A Study on Vataliya Prajapati was published earlier but heterozygous females were not identified. AIMS: To compare incidence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in random and unrelated subjects, present and previous study and as per their original habitat. Incidence of heterozygous deficiency and clinical implication of deficiency was also determined. SETTINGS AND DESIGN: Camps were organized in Katargaon and Amroli regions. Blood specimens, with relevant demographic information, were collected from those who attended the camp. METHODS AND MATERIAL: A total of 1644 random blood samples were collected from 404 families participating in the camps. Nitroblue tetrazolium dye test was used for G6PD deficiency screening and quantitative assay for measurement of G6PD enzyme activity. STATISTICAL ANALYSIS USED: Chi2 test was used to evaluate significance and mean values were compared by the Student's ''t'' test. RESULTS: Incidence of G6PD deficiency was found as 22% among all the random samples tested. However, the G6PD deficiency among unrelated members was 27.9% in males and 12.4% (P< 0.001,df 1). The 13.9% of the females with heterozygous G6PD deficient status, together with the homozygous deficient phenotype makes the incidence comparable with males. Incidence of deficiency was comparable with previous study, in Katargam and Amroli and in Amerli and Bhavganar districts. Deficient subjects had mild anemia and hemolytic crisis rarely occurred. CONCLUSION: Vataliya Prajapatis have high incidence of G6PD deficiency without severe chronic hemolytic anemia. However before prescribing medicines physician should know the G6PD status of a Vataliya Prajapati patient.

Semiquantitative screening test for G6PD deficiency detects severe deficiency but misses a substantial proportion of partially-deficient females.

Neonatal screening for G6PD deficiency has long been established in many countries. The aim of the study was to determine whether the routine semiquantitative fluorescent spot test could detect all cases of G6PD deficiency, including those cases with partial deficiency (residual red cell G6PD activity between 20-60% of normal). We compared the results of G6PD screening by the semiquantitative fluorescent spot test and quantitative G6PD activity assay on a group of 976 neonates and 67 known female heterozygotes. The values for mean G6PD activity of G6PD-normal neonates and 293 healthy adult females were determined. There was no significant difference in the mean normal G6PD activity between the two racial groups in the neonates (669 Malays, 307 Chinese) and in the 293 healthy adult females (150 Malays, 143 Chinese) group. The values for the upper limits of total deficiency (20% of normal residual activity) for neonates and adult females were 2.92 U/gHb and 1.54 U/gHb, respectively. The upper limits of partial deficiency (60% of normal residual activity) were 8.7 U/gHb and 4.6 U/gHb respectively. The prevalence of G6PD deficiency among the male neonates was 5.1% (26) by both the fluorescent spot test and the enzyme assay method. The G6PD activity levels of all 26 cases of G6PD-deficient male neonates were < 20% normal (severe enzyme deficiency). In the female neonate group, the frequency of G6PD deficiency was 1.3% (6 of 472) by the fluorescent spot test and 9.35% (44 of 472) by enzyme assay. The 6 cases diagnosed as deficient by the fluorescent spot test showed severe enzyme deficiency (< 2.92 U/gHb). The remaining 38 female neonates had partial enzyme deficiency and all were misdiagnosed as normal by the fluorescent spot test. In the female heterozygote group, G6PD deficiency was diagnosed in 53% (35 of 67) by enzyme assay and in 7.5% (4 of 67) of cases by the fluorescent spot test. The 4 cases detected by fluorescent spot test had severe enzyme deficiency (<1.6 U/gHb). The remaining 31 (46.3%) cases, diagnosed as normal by fluorescent spot test, showed partial G6PD deficiency. In conclusion, we found that the semiquantitative fluorescent spot test could only diagnose cases of total G6PD deficiency and misclassified the partially-deficient cases as normal. In this study, the overall prevalence of G6PD deficiency was 3.28% by the semiquantitative fluorescent spot test and 7.17% by enzyme assay. This means that 3.9% of G6PD-deficient neonates were missed by the routine fluorescent spot test and they were found to be exclusively females. This study demonstrates a need to use a method that can correctly classify female heterozygotes with partial G6PD deficiency. The clinical implication is that these individuals may be at risk of the hemolytic complication of G6PD deficiency.

Glucose-6-phosphate dehydrogenase deficiency in blood donors: screening by micromethaemoglobin reduction test.

500 blood donors were screened for G6PD deeiciency using micromethaemoglobin reduction (microMRT) test. Most of the blood donors were young adult males (95.8%). The overall incidence of G6PD deficiency was found to be 0.8%. There, was apparently decreased frequency of G6PD deficient blood donors with increasing age, and no relation could be ascertained between G6PD) deficiency and blood groups.

Epidemiological, clinical and laboratory studies of favism [G6PD] in children

This study reports the epidemiological analysis, clinical presentation, laboratory findings and progress of fifty children admitted to "Al-Mansur Teaching Children Hospital", "Saddam's Medical City" during the period from 1st. January 1990 - 31st December 1994, with G6PD deficiency and acute hemolytic anemia after fava bean ingestion. No cases of favism were observed in breast fed babies whose mothers had eaten fava beans, or from pollen inhalation. 10% of the patients had a previous similar attack, 18% had a family history of favism. [86%] of the patients were males. The main age group affected was 2-4 years [66%]. 90% of cases were from Urban and 10% were from Rural areas. 76% presented during the fava bean season, the onset of symptoms started within three days after fava bean ingestion in 94%, the mean value of Hb was 6gm/dl, Hct 19.9%, Reticulocyte count 8.2%, Total bilirubin 5.2mg/dl, Indirect bilirubin 4.3mg/dl. All patients received blood transfusion and achieved good progress

Serum transcobalamin II level in glucose-6-phosphate dehydrogenase deficient subjects with typhoid fever.

Transcobalamin II (TCII) is the vitamin B12 binding protein which is responsible for delivery of this vitamin to the tissues. High values for serum TCII have been reported in many clinical conditions. This paper describes the elevated serum TCII levels in three G-6-PD deficient patients with typhoid fever. They had severe hemolysis with hemoglobinuria associated with slight liver dysfunctions but without obvious increased serum creatinine and BUN concentrations. A remarkable increase in serum TCII level was observed during active hemolysis and decreased to the normal level within 2-3 days after hemolysis ceased. The mechanism of increased serum TCII during hemolysis is probably due to hemoglobinuria secondary to excessive hemolysis. As Hb is known to be efficiently reabsorbed by the proximal tubule cells and can competitively inhibit the tubular uptake of TCII-B12. It is possible that excess Hb interferes with TCII uptake and degradation at renal tubular cells. Therefore, the circulating TCII survival is prolonged resulting in the elevated TCII level. Furthermore, lysosomal degradation of newly synthesized TCII is a normal process that regulates the TCII secretion. Therefore, a reduced lysosome-mediated uptake of TCII-B12 by renal tubular cell may stimulate the TCII secretion as has been shown experimentally in vitro.

An epidemiological study of G-6-PD deficiency, sickle cell haemoglobin, and ABO blood groups in relation to malaria incidence in Muslim and Christian communities of Kheda, Gujarat, (India).

783 blood samples for the study of distribution of ABO blood groups and sickle cell haemoglobin in relation to malaria, from both the sexes of Muslim and Christian populations of Kheda district were screened. 414 blood samples from male individuals were screened for G-6-PD deficiency. High frequency of G-6-PD deficiency was observed in Christians (5.9%) and low in Muslim (1.8%) population, whereas sickle cell haemoglobin in Muslim population was 1.5% and absent in Christians. Blood group B was dominant in both the communities. Significant association of ABO polymorphs with P. falciparum and total malaria cases was observed.

G-6PD deficiency in malaria endemic areas of Udaipur District in Rajasthan.

Nine thousand four hundred thirty three pyrexial cases were screened for the evidence of Malaria and Glucose-6-phosphate dehydrogenase deficiency among the rural tribal population of seven primary health centres in the malarial endemic areas of Udaipur District in Southern Rajasthan. One thousand four hundred five (P. Falciparum 831 and P. Vivax 574) cases were positive for malaria and 170 for G-6PD deficiency. Incidence of G-6PD deficiency in malaria, when compared to the non-malarial cases revealed statistically insignificant alterations (X2 is calculated to 0.1299 which for 1 degree of freedom gives P > 0.05).

Erythrocyte glucose-6-phosphate dehydrogenase and pyruvate kinase activities in hemoglobin H disease.

Erythrocyte glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) activities were studied in hemoglobin H (HbH) patients by spectrophotometric method, cytochemical method and the methemoglobin reduction (MR) test for the detection of heterozygous G6PD deficiency. G6PD deficiency was found in 7 of 64 cases (10.9%), including 3 cases of genotype alpha 1/alpha 2 and 4 cases of genotype alpha 1/CS. None of the HbH patients was found to be PK-deficient. Spectrophotometrically determined G6PD and PK activities were significantly higher in HbH patients than in normals (p less than 0.001), whereas the MR test yielded a significantly lower percentage of residual methemoglobin in HbH patients than in normals (p less than 0.05). All three methods were efficient in the detection of hemizygous G6PD deficiency in HbH patients, but not in G6PD-deficient females.

Erythrocytic glucose-6-phosphate dehydrogenase deficiency in the Bania community of Punjab.

Five hundred members belonging to the Bania community of Punjab were screened for erythrocytic glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. The incidence of enzyme deficiency in males was 2.84 per cent and in females 2.75 per cent, with an overall incidence of 2.80 per cent. No correlation between age and G-6-PD deficiency was found. The mean values for haemoglobin and haematocrit did not differ significantly in the normal and deficient subjects. Study of the deficiency pattern amongst family members of the enzyme deficient subjects confirmed the X-linked inheritance of G-6-PD deficiency.

Neonatal jaundice and glucose-6-phosphate dehydrogenase deficiency.

Ninety-six newborn aged 0-7 days with serum bilirubin of more than 15 mg/dl were studied for the G6PD status using semiquantitative and the assay method. It was found that the result of the 2 methods corresponded. The prevalence of G6PD deficiency was 12.4 per cent (there were 11 boys and one girl). Among the G6PD deficiency and the normal group, there was no difference in the age of the patient, onset of jaundice, bilirubin level, hematocrit status and the reticulocyte count. The semiquantitative method is a reliable as the assay method.