Acalypha indica -induced transient glucose-6-phosphate dehydrogenase deficiency with acute haemolysis.

Acalypha indica is a tropical herb found in Asia. The entire plant, especially the leaves, is used in herbal medicine for several therapeutic purposes. Acute intravascular haemolysis and methaemoglobinaemia have been reported in patients who consume this herb. We present a case of a previously healthy middle-aged man who ingested boiled leaves of A. indica The patient developed clinical symptoms and signs of intravascular haemolysis 7 days after ingestion. Peripheral blood smear showed typical findings of glucose-6-phosphate dehydrogenase (G6PD) deficiency with acute haemolysis. The G6PD activity was low during active haemolysis. The G6PD level, however, returned to normal after 4 months of follow-up. The patient was further tested for common G6PD gene mutations in Southeast Asia and was negative. Ingestion of A. indica may induce transient G6PD deficiency, which in this patient led to acute haemolysis and methaemoglobinaemia.

Exercise in Glucose-6-Phosphate Dehydrogenase Deficiency: Harmful or Harmless? A Narrative Review.

OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, theoretically, renders red blood cells (RBC) susceptible to oxidative stress. G6PD deficiency has also been found in other types of cells than RBC, such as leukocytes and myocytes, where an inefficient protection against oxidative stress may occur too. Glutathione (GSH), a significant antioxidant molecule, levels are lower in G6PD individuals, and theoretically, the probability of oxidative stress and haemolysis due to exercise in individuals with G6PD deficiency is increased, whereas dietary supplementation with antioxidants may have beneficial effects on various aspects of this enzymopathy. METHODS: A search of the available literature was conducted using the keywords glucose-6-phosphate dehydrogenase (G6PD), deficiency, disease, exercise, muscle, antioxidant, vitamin, supplement, and supplementation. The search was limited to publications in English, conducted on humans, and published until August 2018. After screening, only relevant articles were included. RESULTS: There is little evidence indicating that G6PD deficiency can cause perturbations in redox status, haemolysis, and clinical symptoms such as fatigability and myoglobinuria, especially after intense exercise, compared to individuals with normal enzyme levels. CONCLUSIONS: Exercise could be used by G6PD-deficient individuals as a tool to improve their quality of life. However, there is a lack of training studies, and assessment of the effects of regular and systematic exercise in G6PD-deficient individuals is warranted. Finally, since GSH levels are lower in G6PD deficiency, it would be interesting to examine the effects of antioxidant or cysteine donor supplements on redox status after exercise in these individuals.

Readmission for neonatal hyperbilirubinemia in an area with a high prevalence of glucose-6-phosphate dehydrogenase deficiency: A hospital-based retrospective study.

BACKGROUND: Hyperbilirubinemia is one of the most common causes of neonatal readmission to hospital. AIMS: To assess risk factors for hyperbilirubinemia among neonates readmitted for this condition and the ratio of the mean corpuscular hemoglobin concentration (MCHC) to the mean corpuscular volume (MCV). METHODS: We retrospectively studied the clinical and laboratory findings, management and possible risk factors for hyperbilirubinemia in 301 neonates born at ≥35 weeks gestation and readmitted to hospital owing to hyperbilirubinemia over five years. RESULTS: No risk factors for hyperbilirubinemia were identified in 64 (21.3%) neonates, and one or more risk factors were found in 237 neonates (78.7%). The most prevalent risk factor (41.9%) was G6PD deficiency, which occurred in 11 of the 15 neonates with a serum bilirubin level ≥427 µmol/l. A double-volume exchange blood transfusion was performed in two neonate boys in whom G6PD deficiency was the single risk factor for hyperbilirubinemia. One of them developed kernicterus later. The MCHC/MCV ratio of neonates with idiopathic hyperbilirubinemia, unexplained hemolysis, or other risk factors overlapped. CONCLUSIONS: This study confirmed that in an area where G6PD deficiency is prevalent, it is the most common and most severe risk factor for hyperbilirubinemia. This finding supports routine neonatal screening for G6PD deficiency in such areas. The usefulness of determining the MCHC/MCV ratio in the management of hyperbilirubinemia is uncertain.

Association between G6PD deficiency and hyperbilirubinemia in neonates: a meta-analysis.

Hyperbilirubinemia is prevalent in newborns and multiple factors are responsible for the occurrence of neonatal hyperbilirubinemia. G6PD (Glucose-6-Phosphate Dehydrogenase) deficiency is recognized as one of the risk factors. However, many pediatricians did not take into account the probable effect of G6PD-deficiency when severe neonatal hyperbilirubinemia occurred. The aim of the present study was to perform a meta-analysis to investigate whether G6PD-deficiency increases the risk of hyperbilirubinemia and phototherapy in newborn. We searched PubMed and Embase databases for eligible articles according to explicit study inclusion and exclusion criteria. Risk ratios (RRs) and 95% confidence interval (CI) were selected as the evaluation indexes. Cochrane Q and I(2) test were utilized to assess the heterogeneity among studies. A total of five cohort studies were included in this meta-analysis. There were 21,585 participants enrolled in these studies including 877 newborns with hyperbilirubinemia and 261 newborns receiving phototherapy. Comparison of the incidence of hyperbilirubinemia in newborns with G6PD-deficiency to the ones with normal G6PD in each study yielded a pooled RR of 3.92 (95% CI, 2.13-7.20; P <.0001). The pooled RR of receiving phototherapy in G6PD-deficiency neonates is 3.01 (95% CI, 2.20-4.12; P <.0001) when compared to G6PD normal neonates. This study revealed a significant correlation between G6PD-deficiency and neonatal hyperbilirubinemia, as well as G6PD-deficiency and phototherapy. G6PD-deficient newborns have higher risk of hyperbilirubinemia and phototherapy than the ones with normal G6PD. Monitoring the level of G6PD in newborns is important for predicting the occurrence of hyperbilirubinemia.

Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity.

Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an important class of antimalarial/antiinfective therapeutics. However, there is no suitable animal model that can predict the clinical hemolytic potential of drugs. We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors. Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic toxicity (pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations.

Nonimmune hydrops fetalis caused by G6PD deficiency hemolytic crisis and congenital dyserythropoietic anemia.

We present a case of a female neonate who had a nonimmune hydrops fetalis and severe hemolytic anemia due to a rare combination of glucose-6-phosphate dehydrogenase (G6PD) deficiency and congenital dyserythropoietic anemia. We conclude that in severe cases with persistent anemia one should search after delivery for a second reason other than G6PD deficiency alone.

Implementation and analysis of a pilot in-hospital newborn screening program for glucose-6-phosphate dehydrogenase deficiency in the United States.

OBJECTIVE: The purpose of this study was to analyze a targeted screening program for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDdef) and clinical outcomes of G6PD-deficient vs G6PD normal newborns. STUDY DESIGN: Retrospective chart review for 1578 male newborns was performed. The study group was those screened for G6PDdef. Comparisons between G6PD-deficient and normal infants were made with χ (2)-test and unpaired t-test. RESULT: A total of 1095 male newborns were screened, 11.1% had G6PDdef. 97.8% of screen results were reported by 48 h. Total bilirubin (TB) levels in deficient infants were significantly higher than in normal infants throughout birth hospitalization and they were more likely to receive phototherapy. Nineteen screened newborns were rehospitalized for hyperbilirubinemia, 47% had G6PDdef. CONCLUSION: In-hospital newborn screening for G6PDdef with rapid turnaround time is possible. G6PDdef is a risk factor for hyperbilirubinemia in American newborns. US centers with large at-risk populations can identify newborns at risk for severe hyperbilirubinemia with similar screening.

Massive acute haemolysis and severe neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient preterm triplets.

Premature triplets (2 boys and 1 girl) were delivered at 34 weeks, with both boys identified as Glucose-6-phosphate dehydrogenase (G6PD) deficient. Despite having similar quantitative levels of G6PD in their cord blood, only one boy had severe hyperbilirubinemia and anaemia caused by acute haemolysis requiring exchange transfusion. G6PD-deficient infants with the similar genetic, demographic, maternal, clinical factors and G6PD quantification levels can have different severity of presentation of neonatal jaundice in similar environmental set up. This supports the massive acute haemolysis can occur in infant with G6PD deficiency in the absence of any obvious blood group incompatibilities, infection, or ingestion of oxidising agents known to trigger haemolysis.

Glucose-6-phosphate dehydrogenase deficiency in neonatal indirect hyperbilirubinemia.

The aim of this article is to investigate the prevalence of Glucose-6-phosphate dehydrogenase (G6PD) deficiency in neonatal hyperbilirubinemia and to compare the clinical presentation and course of G6PD-deficient and normal patients. This study included a total of 624 term neonates with indirect hyperbilirubinemia from March 2001 to September 2004. Birth weight, sex, weight at admission, serum bilirubin at admission, maximum bilirubin, phototherapy duration, duration of hospitalization and the need for exchange transfusion were recorded. Laboratory evaluations included blood group typing of mother and newborn, complete blood count, peripheral blood smear, serum total and direct bilirubin, direct coombs test, reticulocyte count, serum-free T4 and TSH, urine analysis, urinary reducing substance and erythrocyte G6PD level. The analysis of the results indicated that 24 neonates with indirect hyperbilirubinemia were G6PD-deficient. No statistically significant difference was detected between G6PD-deficient and normal groups in relation to the time of onset of jaundice, reticulocyte count, hematocrit level, phototherapy duration and duration of hospitalization. Serum bilirubin at admission, maximum serum bilirubin level and the need for exchange transfusion were higher in G6PD-deficient group. From this study our conclusion is that the G6PD deficiency is a common enzyme defect causing severe indirect hyperbilirubinemia which may result in kernicterus. Early neonatal screening programmes should be instituted in countries where the deficiency is prevalent.

Diagnosis and management of G6PD deficiency.

Glucose-6-phosphate dehydrogenase deficiency, the most common enzyme deficiency worldwide, causes a spectrum of disease including neonatal hyperbilirubinemia, acute hemolysis, and chronic hemolysis. Persons with this condition also may be asymptomatic. This X-linked inherited disorder most commonly affects persons of African, Asian, Mediterranean, or Middle-Eastern descent. Approximately 400 million people are affected worldwide. Homozygotes and heterozygotes can be symptomatic, although the disease typically is more severe in persons who are homozygous for the deficiency. The conversion of nicotinamide adenine dinucleotide phosphate to its reduced form in erythrocytes is the basis of diagnostic testing for the deficiency. This usually is done by fluorescent spot test. Different gene mutations cause different levels of enzyme deficiency, with classes assigned to various degrees of deficiency and disease manifestation. Because acute hemolysis is caused by exposure to an oxidative stressor in the form of an infection, oxidative drug, or fava beans, treatment is geared toward avoidance of these and other stressors. Acute hemolysis is self-limited, but in rare instances it can be severe enough to warrant a blood transfusion. Neonatal hyperbilirubinemia may require treatment with phototherapy or exchange transfusion to prevent kernicterus. The variant that causes chronic hemolysis is uncommon because it is related to sporadic gene mutation rather than the more common inherited gene mutation.

Glucose-6-phosphate dehydrogenase deficiency: a hidden risk for kernicterus.

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, a commonly occurring enzymatic defect, is an important risk factor in the pathogenesis of severe neonatal hyperbilirubinemia. Many of the recently reported cases of kernicterus, even in countries with a low overall incidence of the G-6-PD deficiency such as the United States and Canada, have been found to be enzyme deficient. In many cases the hyperbilirubinemia may be due to acute hemolysis precipitated by exposure to an identifiable chemical trigger, or to infection. In other cases the hemolysis may be mild, the hyperbilirubinemia being due to diminished bilirubin conjugation. An interaction between G-6-PD deficiency and promoter polymorphism for the gene encoding the bilirubin conjugating enzyme, UDP-glucuronosyltranferase 1A1, associated with Gilbert syndrome, has been implicated in the pathogenesis of hyperbilirubinemia. Neonates whose families originated in areas at high risk for G-6-PD deficiency should be vigilantly observed for jaundice. Phototherapy is the mainstay of treatment, with exchange transfusion being performed in those unresponsive to phototherapy. A high degree of physician awareness is essential in the identification and follow-up of these high-risk neonates.

Neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase deficiency in Sephardic-Jewish neonates: incidence, severity, and the effect of phototherapy.

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is frequently associated with neonatal hyperbilirubinemia, and sometimes kernicterus, often in the absence of any identifiable trigger or hematological evidence of hemolysis. The aim of this study was to compare the incidence and severity of, and the effect of phototherapy on, jaundice in G 6-PD-deficient vs G-6-PD-normal neonates in the Sephardic-Jewish community. Healthy term newborns, born to mothers of families stemming from geographic areas known to be "at risk" for G-6-PD deficiency, were screened for the condition and surveyed for hyperbilirubinemia. Seventy-five G-6-PD-deficient neonates formed the study group, while 266 neonates with normal levels of the enzyme formed the control group. Neonates with any other identifiable cause for jaundice were excluded. Phototherapy was commenced when the serum bilirubin levels reached 16 mg/dL (274 mumol/L) or more, and it was discontinued at 12 mg/dL (205 mumol/L) or less. Hyperbilirubinemia developed in 27 (36%) of the deficient neonates (serum total bilirubin greater than 13.9 mg/dL [238 mumol/L]), compared with 50 (18.8%) of control neonates (P = .002), while 20 (26.7%) of the study group required phototherapy, compared with 31 (11.7%) of control neonates (P = .002). Two neonates in the study group required exchange transfusion (serum bilirubin greater than 20 mg/dL [342 mumol/L]), vs 0 in the control group (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Phototherapy for neonatal jaundice in erythrocyte glucose-6-phosphate dehydrogenase-deficient infants.

The effectiveness of phototherapy in the management of neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient infants was studied. "Prophylactic" phototherapy for six continuous days commencing from the first day of life was effective in preventing a significant rise in bilirubin levels in 12 G6PD-deficient infants in the first three days, during which period a rapid rise was observed in a control group of G6PD-deficient infants. The hemoglobin levels on the first and eighth postnatal days were comparable in both groups. "Therapeutic" phototherapy proved equally effective in reducing bilirubin levels in 24 infants with nonhemolytic hyperbilirubinemia and an equal number of infnats with hyperbilirubinemia associated with G6PD deficiency. Phototherapy was efficacious in the prevention or treatment of neonatal hyperbilirubinemia associated with G6PD deficiency; even if its use is prolonged it does not cause hemolysis in such infants.