Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Gia Lai Province, Vietnam.

Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) deficiency is one of the most common X-linked hereditary disorders worldwide. G6PD deficiency provides resistance against severe malaria, but paradoxically, G6PD deficiency is also a stumbling block in fighting against malaria. Primaquine (PQ), a drug for the radical cure of Plasmodium vivax, can cause lethal acute hemolytic anemia in malaria patients with inherited G6PD deficiency. In this study, we analyzed the phenotypic and genotypic G6PD deficiency status in 1721 individuals (963 males and 758 females) residing in three malaria-endemic areas within the Gia Lai province, Vietnam. The G6PD activity in individuals ranged from 3.04 to 47.82 U/g Hb, with the adjusted male median (AMM) of 7.89 U/g Hb. Based on the G6PD activity assay results, no phenotypic G6PD deficiency was detected. However, the multiplex polymerase chain reaction to detect G6PD variations in the gene level revealed that 26 individuals (7 males, 19 females) had Viangchan mutations (871 G > A). Sequencing analyses suggested that all the males were hemizygous Viangchan, whereas one was homozygous, and 18 were heterozygous Viangchan in females. These results suggested a relatively low prevalence of G6PD deficiency mutation rate (1.51%) in the minor ethnic populations residing in the Gia Lai province, Vietnam. However, considering these areas are high-risk malaria endemic, concern for proper and safe use of PQ as a radical cure of malaria is needed by combining a G6PD deficiency test before PQ prescription.

Genetic analysis and molecular basis of G6PD deficiency among malaria patients in Thailand: implications for safe use of 8-aminoquinolines.

BACKGROUND: It was hypothesized that glucose-6-phosphate dehydrogenase (G6PD) deficiency confers a protective effect against malaria infection, however, safety concerns have been raised regarding haemolytic toxicity caused by radical cure with 8-aminoquinolines in G6PD-deficient individuals. Malaria elimination and control are also complicated by the high prevalence of G6PD deficiency in malaria-endemic areas. Hence, accurate identification of G6PD deficiency is required to identify those who are eligible for malaria treatment using 8-aminoquinolines. METHODS: The prevalence of G6PD deficiency among 408 Thai participants diagnosed with malaria by microscopy (71), and malaria-negative controls (337), was assessed using a phenotypic test based on water-soluble tetrazolium salts. High-resolution melting (HRM) curve analysis was developed from a previous study to enable the detection of 15 common missense, synonymous and intronic G6PD mutations in Asian populations. The identified mutations were subjected to biochemical and structural characterisation to understand the molecular mechanisms underlying enzyme deficiency. RESULTS: Based on phenotypic testing, the prevalence of G6PD deficiency (< 30% activity) was 6.13% (25/408) and intermediate deficiency (30-70% activity) was found in 15.20% (62/408) of participants. Several G6PD genotypes with newly discovered double missense variants were identified by HRM assays, including G6PD Gaohe + Viangchan, G6PD Valladolid + Viangchan and G6PD Canton + Viangchan. A significantly high frequency of synonymous (c.1311C>T) and intronic (c.1365-13T>C and c.486-34delT) mutations was detected with intermediate to normal enzyme activity. The double missense mutations were less catalytically active than their corresponding single missense mutations, resulting in severe enzyme deficiency. While the mutations had a minor effect on binding affinity, structural instability was a key contributor to the enzyme deficiency observed in G6PD-deficient individuals. CONCLUSIONS: With varying degrees of enzyme deficiency, G6PD genotyping can be used as a complement to phenotypic screening to identify those who are eligible for 8-aminoquinolines. The information gained from this study could be useful for management and treatment of malaria, as well as for the prevention of unanticipated reactions to certain medications and foods in the studied population.

Field assessment of the operating procedures of a semi-quantitative G6PD Biosensor to improve repeatability of routine testing.

In remote communities, diagnosis of G6PD deficiency is challenging. We assessed the impact of modified test procedures and delayed testing for the point-of-care diagnostic STANDARD G6PD (SDBiosensor, RoK), and evaluated recommended cut-offs. We tested capillary blood from fingerpricks (Standard Method) and a microtainer (BD, USA; Method 1), venous blood from a vacutainer (BD, USA; Method 2), varied sample application methods (Methods 3), and used micropipettes rather than the test's single-use pipette (Method 4). Repeatability was assessed by comparing median differences between paired measurements. All methods were tested 20 times under laboratory conditions on three volunteers. The Standard Method and the method with best repeatability were tested in Indonesia and Nepal. In Indonesia 60 participants were tested in duplicate by both methods, in Nepal 120 participants were tested in duplicate by either method. The adjusted male median (AMM) of the Biosensor Standard Method readings was defined as 100% activity. In Indonesia, the difference between paired readings of the Standard and modified methods was compared to assess the impact of delayed testing. In the pilot study repeatability didn't differ significantly (p = 0.381); Method 3 showed lowest variability. One Nepalese participant had <30% activity, one Indonesian and 10 Nepalese participants had intermediate activity (≥30% to <70% activity). Repeatability didn't differ significantly in Indonesia (Standard: 0.2U/gHb [IQR: 0.1-0.4]; Method 3: 0.3U/gHb [IQR: 0.1-0.5]; p = 0.425) or Nepal (Standard: 0.4U/gHb [IQR: 0.2-0.6]; Method 3: 0.3U/gHb [IQR: 0.1-0.6]; p = 0.330). Median G6PD measurements by Method 3 were 0.4U/gHb (IQR: -0.2 to 0.7, p = 0.005) higher after a 5-hour delay compared to the Standard Method. The definition of 100% activity by the Standard Method matched the manufacturer-recommended cut-off for 70% activity. We couldn't improve repeatability. Delays of up to 5 hours didn't result in a clinically relevant difference in measured G6PD activity. The manufacturer's recommended cut-off for intermediate deficiency is conservative.

Glucose-6-phosphate dehydrogenase deficiency and psychotic disorders: A systematic review.

OBJECTIVES: Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) is the most common enzymopathy globally. Early studies suggested an association with severe psychotic illness; however, changes to laboratory testing and diagnostic classification renders the association unclear. This study aims to explore the interaction between G6PD deficiency and psychotic symptoms, in particular to identify specific patterns of presentation or impact on outcomes. METHODS: Pubmed, Embase, and PsycInfo databases were searched from inception to May 2023. Descriptive statistics and narrative review of were used to synthesise data on demographics, mental and physical health diagnoses, investigations, treatment, and outcomes. RESULTS: No clear link was found in published data (eight case reports, case series of n = 29) with a high rate (63%) of haemolytic crisis at the time of psychiatric presentation suggested delirium as an alternative diagnosis. Four case control studies found no significant difference in the prevalence of G6PD deficiency. However, catatonic presentation was reported in 40% of the case series and a higher prevalence of G6PD deficiency in catatonic schizophrenia was noted in case control studies. CONCLUSIONS: Based on the information available there was no clear association between G6PD deficiency and psychotic illness or treatment resistance, although paucity of studies and risk of bias limit strong conclusions.

Screening results and mutation frequency analysis of G6PD deficiency in 1,291,274 newborns in Huizhou, China: a twenty-year experience.

OBJECTIVES: This study aimed to investigate the incidence rate and spectrum of gene mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Huizhou city of southern China to provide a scientific basis for disease prevention and control in the area. METHODS: From March 2003 to December 2022, newborn screening for G6PD enzyme activity was carried out in Huizhou city using the fluorescence quantitative method. Infants who tested positive during the initial screening were diagnosed using the nitroblue tetrazolium ratio method, while a subset of infants received further gene mutation analysis using the multicolor probe melting curve analysis method. RESULTS: A total of 1,291,274 newborns were screened and the screening rate has increased from 20.39% to almost 100%. In the 20-year period, 57,217 (4.43%) infants testing positive during the initial screening. Out of these infants, 49,779 (87%) were recalled for confirmatory testing. G6PD deficiency was confirmed in 39,261 of the recalled infants, indicating a positive predictive value of 78.87%. The estimated incidence rate of G6PD deficiency in the region was 3.49%, which was significantly higher than the average incidence rate of 2.1% in southern China. On the other hand, seven pathogenic G6PD variants were identified in the analysis of the 99 diagnosed infants with the most common being c.1388 G > A (48.5%), followed by c.95 A > G (19.2%), c.1376 G > T (15.2%), c.871 G > A (9.1%), c.1360 C > T (3.0%), c.392 G > T (3.0%), and c.487 G > A (1.0%). CONCLUSION: The incidence of G6PD deficiency in newborns in the Huizhou city was higher than the southern China average level, while the types and frequencies of gene mutations were found to vary slightly from other regions. Our findings suggested that free government screening and nearby diagnosis strategies could reduce the incidence of G6PD deficiency in the area.

Prevalence of G6PD deficiency and submicroscopic malaria parasites carriage in malaria hotspot area in Northwest, Tanzania.

BACKGROUND: The use of primaquine for mass drug administration (MDA) is being considered as a key strategy for malaria elimination. In addition to being the only drug active against the dormant and relapsing forms of Plasmodium vivax, primaquine is the sole potent drug against mature/infectious Plasmodium falciparum gametocytes. It may prevent onward transmission and help contain the spread of artemisinin resistance. However, higher dose of primaquine is associated with the risk of acute haemolytic anaemia in individuals with a deficiency in glucose-6-phosphate dehydrogenase. In many P. falciparum endemic areas there is paucity of information about the distribution of individuals at risk of primaquine-induced haemolysis at higher dose 45 mg of primaquine. METHODS: A retrospective cross-sectional study was carried out using archived samples to establish the prevalence of G6PD deficiency in a malaria hotspot area in Misungwi district, located in Mwanza region, Tanzania. Blood samples collected from individuals recruited between August and November 2010 were genotyped for G6PD deficiency and submicroscopic parasites carriage using polymerase chain reaction. RESULTS: A total of 263 individuals aged between 0 and 87 were recruited. The overall prevalence of the X-linked G6PD A- mutation was 83.7% (220/263) wild type, 8% (21/263) heterozygous and 8.4% (22/263) homozygous or hemizygous. Although, assessment of the enzymatic activity to assign the phenotypes according to severity and clinical manifestation as per WHO was not carried out, the overall genotype and allele frequency for the G6PD deficiency was 16.4% and 13. 2%, respectively. There was no statistically significant difference in among the different G6PD genotypes (p > 0.05). Out of 248 samples analysed for submicroscopic parasites carriage, 58.1% (144/248) were P. falciparum positive by PCR. G6PD heterozygous deficiency were associated with carriage of submicroscopic P. falciparum (p = 0.029). CONCLUSIONS: This study showed that 16.4% of the population in this part of North-western Tanzania carry the G6PD A- mutation, within the range of 15-32% seen in other parts of Africa. G6PD gene mutation is widespread and heterogeneous across the study area where primaquine would be valuable for malaria control and elimination. The maps and population estimates presented here reflect potential risk of higher dose of primaquine being associated with the risk of acute haemolytic anaemia (AHA) in individuals with a deficiency in glucose-6-phosphate dehydrogenase and call further research on mapping of G6PD deficiency in Tanzania. Therefore, screening and education programmes for G6PD deficiency is warranted in a programme of malaria elimination using a higher primaquine dose.

Prevalence and molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Senoi Malaysian Orang Asli population.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder characterized by reduced G6PD enzyme levels in the blood. This condition is common in populations exposed to malaria; an acute febrile disease caused by Plasmodium parasites. G6PD-deficient individuals may suffer from acute hemolysis following the prescription of Primaquine, an antimalarial treatment. The population at risk for such a condition includes the Senoi group of Orang Asli, a remote indigenous community in Malaysia. This study aimed to elucidate the G6PD molecular heterogeneity in this subethnic group which is important for malaria elimination. A total of 662 blood samples (369 males and 293 females) from the Senoi subethnic group were screened for G6PD deficiency using a quantitative G6PD assay, OSMMR2000-D kit with Hb normalization. After excluding the family members, the overall prevalence of G6PD deficiency in the studied population was 15.2% (95% CI: 11-19%; 56 of 369), with males (30 of 172; 17.4%) outnumbering females (26 of 197; 13.2%). The adjusted male median (AMM), defined as 100% G6PD activity, was 11.8 IU/gHb. A total of 36 participants (9.6%; 26 male and 10 female) were deficient (<30% of AMM) and 20 participants (5.4%; 4 male and 16 female) were G6PD-intermediate (30-70% of AMM). A total of 87 samples were genotyped, of which 18 showed no mutation. Seven mutations were found among 69 genotyped samples; IVS11 T93C (47.1%; n = 41), rs1050757 (3'UTR +357A>G)(39.1%; n = 34), G6PD Viangchan (c.871G>A)(25.3%; n = 22), G6PD Union (c.1360C>T)(21.8%; n = 19), c.1311C>T(20.7%; n = 18), G6PD Kaiping (c.1388G>A)(8.0%; n = 7), and G6PD Coimbra (c.592C>T)(2.3%; n = 2). Our analysis revealed 27 hemizygote males, 18 heterozygote females, 7 homozygote females, and 2 compound heterozygote females. This study confirms the high prevalence of G6PD deficiency among the Senoi Malaysian Orang Asli, with a significant degree of molecular heterogeneity. More emphasis should be placed on screening for G6PD status and proper and safe use of Primaquine in the elimination of malaria among this indigenous population.

Molecular characterization of G6PD mutations identifies new mutations and a high frequency of intronic variants in Thai females.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy caused by mutations in the G6PD gene. A medical concern associated with G6PD deficiency is acute hemolytic anemia induced by certain foods, drugs, and infections. Although phenotypic tests can correctly identify hemizygous males, as well as homozygous and compound heterozygous females, heterozygous females with a wide range of G6PD activity may be misclassified as normal. This study aimed to develop multiplex high-resolution melting (HRM) analyses to enable the accurate detection of G6PD mutations, especially among females with heterozygous deficiency. Multiplex HRM assays were developed to detect six G6PD variants, i.e., G6PD Gaohe (c.95A>G), G6PD Chinese-4 (c.392G>T), G6PD Mahidol (c.487G>A), G6PD Viangchan (c.871G>A), G6PD Chinese-5 (c.1024C>T), and G6PD Union (c.1360C>T) in two reactions. The assays were validated and then applied to genotype G6PD mutations in 248 Thai females. The sensitivity of the HRM assays developed was 100% [95% confidence interval (CI): 94.40%-100%] with a specificity of 100% (95% CI: 88.78%-100%) for detecting these six mutations. The prevalence of G6PD deficiency was estimated as 3.63% (9/248) for G6PD deficiency and 31.05% (77/248) for intermediate deficiency by phenotypic assay. The developed HRM assays identified three participants with normal enzyme activity as heterozygous for G6PD Viangchan. Interestingly, a deletion in intron 5 nucleotide position 637/638 (c.486-34delT) was also detected by the developed HRM assays. G6PD genotyping revealed a total of 12 G6PD genotypes, with a high prevalence of intronic variants. Our results suggested that HRM analysis-based genotyping is a simple and reliable approach for detecting G6PD mutations, and could be used to prevent the misdiagnosis of heterozygous females by phenotypic assay. This study also sheds light on the possibility of overlooking intronic variants, which could affect G6PD expression and contribute to enzyme deficiency.

Clinical performance validation of the STANDARD G6PD test: A multi-country pooled analysis.

INTRODUCTION: Screening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency. METHODS AND FINDINGS: Data from similar clinical studies evaluating the performance of the STANDARD G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%-100%) for G6PD deficient cases with <30% activity and 77% (95% CI 66.8%-85.4%) for females with intermediate activity between 30%-70%. Specificity was 98.1% (95% CI 97.6%-98.5%) and 92.8% (95% CI 91.6%-93.9%) for G6PD deficient individuals and intermediate females, respectively. Out of 20 G6PD intermediate females with false normal results, 12 had activity levels >60% on the reference assay. The negative predictive value for females with G6PD activity >60% was 99.6% (95% CI 99.1%-99.8%) on capillary specimens. Sensitivity among 396 P. vivax malaria cases was 100% (69.2%-100.0%) for both deficient and intermediate cases. Across the full dataset, 37% of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, over 95% of cases would receive correct treatment with primaquine, over 87% of cases would receive correct treatment with tafenoquine, and no true G6PD deficient cases would be treated inappropriately based on the result of the STANDARD G6PD Test. CONCLUSIONS: The STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.

Mutation spectrum and enzyme profiling of G6PD deficiency in neonates of north India: a prospective study.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked disorder with well-established clinical and allelic heterogeneity and ethnic disparity. With ~390,000 annual births with G6PD deficiency in India, it emerges as the most predictable and preventable inbornmetabolic error. Disease prevalence and mutation spectrum have been reasonably reported fromcentral, western and southern parts of India and are mostly retrospective studies.Although prevalence data fromnorth India is available, there is paucity of data on the mutation spectrum and genotype-phenotype correlation (GxP). Thus, we aimed at establishing the clinical and mutation profiles for G6PD, as a part of a large prospective newborn screening study conducted between 2014 and 2016 across hospitals in Delhi, India. G6PD activity levels were measured at 24-48 h of life for ~200,000 neonates using Victor 2D and/or Genomic Screening Processor followed by confirmatory spectrophotometric analysis usingRBClysates of the respective neonates based on clinical symptoms.Asubset of 570 enzyme deficient neonates were screened formutations by polymerase chain reaction-restriction fragment length polymorphismand/or Sanger sequencing.Mediterraneanwas the most common mutation (n=318; 55.8%) with the lowest enzyme activity and most severe phenotype, followed by G6PD Orissa (n=187;32.8%); Kerala-Kalyan (n=25); Jammu (n=24);Mahidol (n=14); Chattam(n=1) andNilgiri/Coimbra (n=1).Of the 163 intramural neonates followed up, 68 developed clinical jaundice. However, no correlation was observed between jaundice and enzyme level. Notable outcome of this first ever prospective screening approach for G6PD deficiency in neonates may help in prediction of disease severity and appropriate timely management.

Glucose-6-Phosphate Dehydrogenase Deficiency and Coronavirus Disease 2019.

In this cohort study conducted in a national healthcare organization in Israel, we found that individuals with glucose-6-phosphate dehydrogenase deficiency had an increased risk of coronavirus disease 2019 (COVID-19) infection and severity, with higher rates of hospitalization and diagnosed long COVID.

Identification of Glucose-6 Phosphate Dehydrogenase Deficient Patients Using Attenuated Total Reflection Fourier Transform Infrared Spectroscopy Using Partial Least Squares Discriminant Analysis in Aqueous Blood Samples.

Glucose-6 phosphate dehydrogenase (G6PD) deficiency is an X-linked blood disease that affects 400 million people globally and is especially prevalent in malaria-endemic regions. A significant portion of carriers are asymptomatic and undiagnosed posing complications in the eradication of malaria as it restricts the types of drugs used for malaria treatment. A simple and accurate diagnosis of the deficiency is vital in the eradication of malaria. In this study, we investigate the potential of attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) as a diagnostic technique for G6PD deficiency. Venous blood samples were collected in lithium heparin anticoagulant tubes from G6PD partial and fully deficient volunteers, n = 17, and normal volunteers, n = 59, in Khon Kaen, Thailand. Spectra of aqueous and dry samples were acquired of whole blood, plasma, and red blood cells, and modeled using partial least squares discriminant analysis (PLS-DA). PLS-DA modeling resulted in a sensitivity of 0.800 and specificity of 0.800 correctly classifying fully deficient participants as well as a majority of partially deficient females who are often misdiagnosed as normal by current screening methods. The viability of utilizing aqueous samples has always been hindered by the variability of hydration in the sample, but by employing multicurve curve resolution-alternating least squares to subtract water from each sample we are able to produce high-quality spectra with minimized water contributions. The approach shows proof of principle that ATR FT-IR combined with multivariate data analysis could become a frontline screening tool for G6PD deficiency by improving tailored drug treatments and ultimately saving lives.

Evaluation of quantitative point-of-care test for measurement of glucose-6-phosphate dehydrogenase enzyme activity in Malaysia.

INTRODUCTION: The treatment of Plasmodium vivax malaria with 8-aminoquinolines is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals due to the risk of acute haemolytic anaemia. Effective G6PD screening is paramount to avoid adverse drug reactions. This study aimed to evaluate the performance of novel quantitative point-of-care (POC) tests as a new screening method for G6PD deficiency in Malaysia. MATERIALS AND METHODS: A total of 153 neonatal cord blood, 99 peripheral blood of older children aged between 1 month to 12-years old, and 62 peripheral adult blood were screened for G6PD deficiency using two quantitative POC tests, CareStartTM biosensor (Carestart) and CareStartTM Biosensor 1 (S1). The results were compared with OSMMR2000D kit as a reference assay. Two statistical analyses were performed in this study to evaluate the POC test performances, the Spearman's correlation test and the Cohen's kappa method. RESULTS: Both Carestart and S1 tests showed significant positive correlations to OSMMRS000D with r2 = 0.7916 and r2 = 0.7467. Their measurement of agreement showed a kappa (κ) value of 0.805 (p<0.001, 95% CI), and 0.795 (p<0.001, 95% CI), respectively. Analysis of the area under the Receiver Operating Curve (ROC) at 60% cut-off illustrated that the Carestart had 90.2% sensitivity, 98.9% specificity, 98.3% positive predictive value (PPV), and 93.8% negative predictive value (NPV). The corresponding values for the S1 were 95.2%, 100%, 100%, and 96.8%, respectively. CONCLUSION: This study showed that the Carestart and S1 biosensors have high-performance reliability for screening of G6PD deficiency, which can guide safe prescriptions of anti-malaria medications and hence, eradication of Plasmodium vivax malaria.

Glucose 6 phosphate dehydrogenase deficiency quantitative test in dried blood spot- a potential marker for adult unknown G6PD deficiency.

Glucose 6 Phosphate Dehydrogenase (G6PD) enzyme activity estimation in a freshly collected blood sample is the most widely used diagnostic method for the diagnosis of G6PD deficiency. The objective is to evaluate the need for newborn screening for G6PD deficiency over post-malarial diagnosis and the feasibility and reliability of using dried blood spots (DBS) as samples for screening. A total of 562 samples were analyzed for G6PD and parallel measurement of G6PD activity by the colorimetric method in whole blood and DBS was carried out in the neonatal subset. Among 466 adults, 27 (5.7%) showed G6PD deficiency, out of whom 22 (81.48%) were diagnosed after the malarial encounter. In the pediatric group, 8 neonates showed G6PD deficiency. G6PD activity estimated from DBS samples agreed with whole blood, with a statistically significant strong positive correlation. Screening of G6PD deficiency at birth to prevent future unwarranted complications, using DBS is feasible.

Is Glucose-6-Phosphate Dehydrogenase Deficiency a Risk Factor for Autoimmune Thyroid Disease? A Retrospective Case-Control Study.

BACKGROUND: The risk of developing thyroid disorders (TDs) in subjects with inherited glucose-6-phosphate dehydrogenase (G6PD) deficiency is unknown. The aim of this study was to explore the association between autoimmune (AITD) and G6PD deficiency in Northern Sardinia, in a population with a high frequency of these two conditions. METHODS: In this retrospective single-center case-control study, demographic and clinical data were collected from patients examined in a tertiary referral Gastroenterology Section of a teaching hospital. RESULTS: In 8894 subjects examined (64.7% females), 1218 patients were diagnosed with TDs; more specifically, 767 were diagnosed with AITD and 451 were not (non-AITD). Overall, G6PD deficiency was more prevalent in TD patients compared with patients without TD (controls) (16.7% vs. 11.2%; p < 0.0001). Multivariable logistic regression analysis (after adjusting for age, sex, excess weight and smoking habits), confirmed a higher risk of AITD among G6PD deficient patients with an odds ratio (OR) of 1.36 and 95% confidence interval (CI) of 1.11-1.6, female patients (OR 1.33, 95% CI 1.07-1.65) and overweight patients (OR 1.22, 95% CI 1.03-1.44). CONCLUSIONS: The risk of AITD is increased in carriers of G6PD deficiency. A careful assessment of thyroid function is advisable in patients with inherited G6PD defects.

Favism: Clinical Features at Different Ages.

Favism is a hemolytic disease due to the ingestion of fava beans in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. There is wide inter- and intra-individual variability in the development of hemolytic crisis, and several factors influence it: quantity, quality, ripeness of fava beans, and age of onset. In this narrative review of case reports and case series, we reported the predisposing factors and clinical features for four different age groups classified as follows: pregnant women and infants (i.e., exclusively breastfed children); children, from weaned to 11 years; preadolescents and adolescents, from 11 to 18 years; and adults (18 years and older). Some symptoms developed only in specific age groups: death in infants; visual impairment in children; systolic murmur in infants, children, and adolescents; and renal failure in adults. In youngest children or pregnant women the severity is the highest. Some other symptoms were present in all: jaundice, increased bilirubin, splenomegaly, hepatomegaly, discolored urine, tachycardia, pallor, abdominal pain, malaise, vomit, nausea, and dizziness. Laboratory findings are characterized by anemia, reticulocytosis, elevated bilirubin level, and sometimes urinary urobilinogen and methemoglobinemia. In most cases the symptomatology is self-limited and does not release sequelae, but hospitalization and transfusion are often required.