Clinical and laboratory features of pediatric patients with glucose-6-phosphate dehydrogenase enzyme deficiency

Objective: The purpose of our study is to investigate the clinical course, diagnostic criteria, and genetic profiles of pediatric patients diagnosed with Glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Manisa region. We aim to analyze the distribution of observed genetic variants in these patients and uncover the relationship between laboratory data and clinical findings. Materials and methods: We retrospectively examined the clinical and laboratory parameters of patients diagnosed with G6PD deficiency due to neonatal jaundice and acute hemolytic attacks at the Manisa Celal Bayar University Hafsa Sultan Hospital Pediatric Hematology Clinic between 2004 and 2022. Factors such as patients' ages at admission, symptoms, hospitalization duration, family history, and transfusion requirements were evaluated using file records and data obtained from the probe system. Additionally, genetic results, hemogram, reticulocyte ratio, bilirubin levels, and G6PD enzyme levels were analyzed. Results: The data of 95 patients diagnosed with G6PD enzyme deficiency were retrospectively analyzed in our study, and their demographic characteristics, presenting clinics, and clinical courses were evaluated in detail. Fifty-eight patients were diagnosed with hemolytic anemia, while 37 patients were diagnosed with neonatal jaundice. Of the patients, 83 (87.4%) were male, and 12 (12.6%) were female, with no difference in gender regarding presenting clinics. The mean age in the hemolytic anemia group was determined to be 3.83±2.81 years (ranging from 1 to 14 years). The average hospitalization duration due to hemolytic attacks was found to be 2.9 days, with 49 patients requiring transfusion. No significant relationship was found between hospitalization duration and G6PD level, lactate dehydrogenase (LDH), corrected reticulocyte ratio, and indirect bilirubin level. There was no significant association between G6PD enzyme level and transfusion requirement or number of transfusions in patients presenting with hemolytic anemia (p: 0.548). However, a negative correlation was observed between G6PD enzyme level and both LDH level (p: 0.016, r: - 0.314) and lymphocyte count (p: 0.034, r: -0.425) in patients presenting with hemolytic anemia. No significant relationship was found between other laboratory parameters and G6PD level. In the hemolytic anemia group, compared to the neonatal jaundice group, Hb, Hct, RBC, MCV, MCH, MPV, total bilirubin, and indirect bilirubin values were significantly lower, while reticulocyte, LDH, WBC, and neutrophil levels were higher (p <0.05). The 62 average hospitalization duration due to neonatal jaundice was 2.49 ± 3.02 days, with the longest hospitalization duration being 13 days. A significant positive correlation was found between the indirect bilirubin level of neonatal patients and hospitalization duration, while no significant relationship was found between G6PD enzyme level and hospitalization duration or hematologic parameters. Genetic analysis results were obtained for 22 patients, revealing six different variants. Four of these variants (Mediterranean, Chatham, Cassano and Union) were classified as Class II, while two (Asahi and Kalyan-Kerala) were classified as Class III. The Mediterranean variant (Ser188Phe) was found in 14 cases, with eight of these patients diagnosed with hemolytic attacks and six with prolonged jaundice. Discussion and Conclusion: Glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency is a commonly encountered enzymopathy in our country. In our study, 61.1% of our patients were diagnosed with hemolytic anemia, and 38.9% with neonatal jaundice. The mean age of patients presenting with hemolytic attacks was 3.83±2.81 years (range 1-14 years), consistent with reports in our country and other academic studies. While G6PD enzyme deficiency manifests more prominently in males due to genetic mutation, in females, it can result in symptoms of varying severity due to both mutation and random X chromosome inactivation. Both in the neonatal jaundice group and the hemolytic attack group, male gender predominance was observed, consistent with the literature. In patients diagnosed with hemolytic anemia, a history of fava bean consumption and previous infections were frequently observed. Complaints of jaundice and pallor were common in patients presenting with hemolytic attacks, with the most common physical examination findings being jaundiced appearance, tachycardia, and fever. In neonatal patients, the most common complaint and physical examination finding was jaundice in the skin and sclera. The presenting complaints and physical examination findings of the patients were similar to those reported in other studies in the literature. The data from our study demonstrated that G6PD enzyme levels did not vary according to gender and presenting clinic, indicating a consistent situation among measurements. Consistent with other studies in the literature, we did not observe a significant effect of G6PD levels on hematologic parameters in neonates with G6PD deficiency. However, in patients with hemolytic anemia, we found a significant negative correlation between low G6PD levels and lymphocyte count, suggesting that increased oxidative stress in patients with G6PD deficiency leads to lymphocyte proliferation. Current studies also support our findings, indicating a need for further research in this area. In patients presenting with hemolytic attacks, a negative relationship was found between G6PD levels and LDH levels, 63 but no correlation was found between LDH levels and the need for erythrocyte transfusion or hospitalization duration. LDH was considered to increase due to increased oxidative stress and increased anaerobic glycolysis as G6PD levels decreased, suggesting that LDH may be a predictive parameter for G6PD enzyme levels, necessitating further comprehensive studies. Laboratory parameters of patients with hemolytic anemia were compared with those of neonatal jaundice groups, revealing significantly lower levels of hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean platelet volume, total and indirect bilirubin, and higher reticulocyte ratio, lactate dehydrogenase, white blood cell, and neutrophil levels in the hemolytic anemia group; these differences were statistically significant (p<0.05). There was no significant difference between the groups in other parameters (p>0.05). The high MCV, MCH, and MPV in neonates were attributed to age-related changes. On the other hand, the high levels of hemoglobin, hematocrit, and total/indirect bilirubin were indicative of liver dysfunction rather than erythrocyte breakdown. The elevation of WBC and neutrophils in hemolytic anemia was linked to rapidly deteriorating red blood cells and increased oxidative stress. We could not find a parameter associated with the need for erythrocyte transfusion in patients presenting with hemolytic attacks. Similarly, there was no parameter that could predict hospitalization duration for the hemolytic anemia group. However, in the neonatal group, hospitalization correlated positively with indirect bilirubin levels, and considering the existence of studies indicating that patients with G6PD deficiency have higher bilirubin levels and a higher risk of developing kernicterus compared to the normal population, we believe that G6PD deficiency should be screened in patients followed up for hyperbilirubinemia. In our study, genetic analysis of 22 patients revealed six different variants, four of which were classified as Class II (Mediterranean, Chatham, Cassano, and Union) and two as Class III (Asahi and Kalyan-Kerala). Especially, the Mediterranean variant was found to be associated with hemolytic attacks and prolonged jaundice, demonstrating that G6PD deficiency is a significant cause of favism and neonatal jaundice in our region. Keywords: Glucose-6-Phosphate Dehydrogenase, neonatal jaundice, acute hemolytic attack, favism