Related Experiment Video
Updated: May 19, 2026
Biochemical Measurement of Neonatal Hypoxia
Published on: August 24, 2011
Neonatal hyperbilirubinemia in infants with G6PD c.563C > T Variant
Bushra Moiz1, Amna Nasir, Sarosh Ahmed Khan
1Department of Pathology and Microbiology, The Aga Khan University Hospital, Karachi, Pakistan. bushra.moiz@aku.edu
Insights
Neonates with the G6PD c.563C > T variant experience earlier and more severe jaundice. This genetic variant is linked to significantly lower glucose-6-phosphate dehydrogenase enzyme activity, increasing hyperbilirubinemia risk.
Area of Science:
- Medical Genetics
- Neonatology
- Biochemistry
Background:
- Neonatal hyperbilirubinemia is frequently associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency, posing a risk of bilirubin encephalopathy.
- In Pakistan, G6PD deficiency affects 4-14% of hospitalized jaundiced neonates, with the G6PD c.563C > T variant being most common.
- This study investigates the clinical implications of the G6PD c.563C > T variant on hyperbilirubinemia onset and progression in infants.
Purpose of the Study:
- To evaluate the time of onset of hyperbilirubinemia in infants with the G6PD c.563C > T variant.
- To analyze the postnatal bilirubin trajectory in infants carrying the G6PD c.563C > T variant.
- To compare clinical and biochemical parameters between neonates with and without the G6PD c.563C > T variant.
Main Methods:
- A case-control study involving 216 icteric male neonates requiring phototherapy was conducted.
- Infants were assessed for clinical factors, bilirubin levels, and treatment. G6PD deficiency was quantified, and genotyping (PCR-RFLP, sequencing) was performed for deficient infants.
- Comparison was made between neonates with the G6PD c.563C > T variant and G6PD normal neonates.
Main Results:
- The G6PD c.563C > T variant was identified in 65% of G6PD deficient infants.
- Infants with the c.563C > T variant exhibited significantly lower G6PD enzyme activity compared to controls.
- These infants also presented with higher peak total serum bilirubin levels that occurred earlier postnatally.
Conclusions:
- Infants with the G6PD c.563C > T variant develop jaundice earlier than those with normal G6PD levels.
- The G6PD c.563C > T variant is associated with significantly reduced G6PD enzyme activity.
- This variant contributes to a more rapid and severe onset of neonatal hyperbilirubinemia.
Background:
There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4-14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T.
Methods:
This was a case-control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing.
Results:
G6PD variants c.563C > T and c.131 C > G were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean ± 1SD; 0.3 ± 0.2 U/gHb vs. 14.0 ± 4.5 U/gHb, p < 0.001) experienced higher peak levels of total serum bilirubin (mean ± 1SD; 16.8 ± 5.4 mg/dl vs. 13.8 ± 4.6 mg/dl, p = 0.008) which peaked earlier after birth (mean ± 1SD 2.9 ± 1.6 vs. 4.3 ± 2.3 days, p = 0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups.
Conclusions:
We concluded that infants with G6PD c.563C > T variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, G6PD c.563C > T carrying infants had significantly low G6PD activity.
Related Concept Videos
01:25Jaundice
01:20Inborn Errors of Metabolism
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
01:27Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
01:31Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life