Clinical features and genetic variations of severe neonatal hyperbilirubinemia: Five case reports

BACKGROUND: Neonatal hyperbilirubinemia is a common problem faced by pediatricians. The role of genetic factors in neonatal jaundice has been gradually recognized. This study aims to identify genetic variants that influence the bilirubin level in five patients using next-generation sequencing (NGS). CASE SUMMARY: Five neonates with severe hyperbilirubinemia were retrospectively studied. They exhibited bilirubin encephalopathy, hypothyroidism, ABO blood type incompatibility hemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency and premature birth, respectively. A customized 22-gene panel was designed, and NGS was carried out for these neonates. Eight variations (G6PD c.G1388A, HBA2 c.C369G, ABCC2 c.C3825G, UGT1A1 c.G211A, SPTB c.A1729G, EPB41 c.G520A, c.1213-4T>G and c.A1474G) were identified in these five neonates. Genetic mutations of these genes are associated with G6PD deficiency, thalassemia, Dubin-Johnson syndrome, Gilbert syndrome, hereditary spherocytosis, and hereditary elliptocytosis. One of the neonates was found to have compound variants of the EPB41 splice site c.1213-4T>G and c.G520A (p.E174K), but no elliptocyte was seen on his blood smear of 4 years old. CONCLUSION: Pathological factors of severe neonatal hyperbilirubinemia are complicated. Genetic variants may play an important role in an increased risk of neonatal hyperbilirubinemia, and severe jaundice in neonates may be related to a cumulative effect of genetic variants.