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

Table 1 Clinical and laboratory characteristics of five neonates with severe hyperbilirubinemia

Case ID	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Gender	Male	Male	Male	Female	Male
Admission time (d)	5	12	4	28	7
Gestational age (wk)	39 + 5	39	40 + 3	40	35 + 4
Birth weight (kg)	3.15	3.1	3.3	3.25	2.65
Mode of delivery	Vaginal	Cesarean	Cesarean	Cesarean	Vaginal
Feeding patterns	Formula	Breast	Breast	Formula	Breast
Postnatal growth ratardation	+	-	-	+	-
Skin and mucous membrane yellowing	+	+	+	+	+
Time of jaundice occur after birth (d)	2	3	3	4	2
Maximum TBIL levels (μmol/L)a	719.5	527.87	429.6	538.7	584.4
Age at maximum TBIL (d)	5	12	4	28	7
Phototherapy	+	+	+	+	+
RBC transfusion	-	+	-	-	-
IVIGb or albumin therapy	+	+	+	-	-
Clinical diagnosis	G6PD deficiency; Congenital hypertrophic pyloric stenosis; Neonatal hyperbilirubinemia	G6PD deficiency; Anemia; Bilirubin encephalopathy	ABO blood type incompatibility hemolytic disease	Congenital hypothyroidism; Neonatal hyperbilirubinemia	Premature delivery; Neonatal hyperbilirubinemia

^aNormal upper limit: 20.1 µmol/L.

^bIntravenous immunoglobulin.

+: Present; -: Absent; TBIL: Total bilirubin; RBC: Red blood cell; IVIG: Intravenous immunoglobulin; G6PD: Glucose-6-phosphate dehydrogenase.

Table 2 Causative mutations and potentially pathogenic variants identified in five neonates

Case numbers	Gene name	rs number	cDNA/protein change	Mutationtaster prediction	PolyPhen2	SIFT	Genotype	Associated disorder
Patient 1	EPB41	rs201231112	c.G520A/p.E174K	Disease-causing	Probably damaging	Tolerated	Hetero	Elliptocytosis
	EPB41	rs188648724	c.1213-4T>G	Disease-causing			Hetero	Elliptocytosis
	G6PD	rs72554664	c.G1388A/p.R463H	Disease-causing	Damaging	Deleterious	Hemiz	G6PD deficiency
Patient 2	G6PD	rs72554664	c.G1388A/p.R463H	Disease-causing	Damaging	Deleterious	Hemiz	G6PD deficiency
	HBA2	rs41479347	c.C369G/p.H123Q	Disease-causing	Probably damaging	Deleterious	Hetero	Thalassemia
Patient 3	EPB41	rs778090351	c.A1474G/p.T492A	Disease-causing	Damaging	Deleterious	Hetero	Elliptocytosis
Patient 4	SPTB	rs144668591	c.A1729G/p.I577V	Disease-causing	Probably damaging	Deleterious	Hetero	Elliptocytosis
	ABCC2	rs554976086	c.C3825G/p.Tyr1275X	Disease-causing	Probably damaging	Deleterious	Hetero	Dubin-Johnson syndrome
Patient 5	UGT1A1	rs4148323	c.G211A/p.G71R	Polymorphism	Probably damaging	Deleterious	Hetero	Gilbert's syndrome

Hetero: Heterozygous; Hemiz: Hemizygote; EPB41: Protein 4.1; G6PD: Glucose-6-phosphate dehydrogenase; HBA2: Hemoglobin alpha 2; SPTB: Spectrin beta; ABCC2: Adenosine triphosphate-binding cassette subfamily C member 2; UGT1A1: Uridine diphosphate glucuronosyltransferase 1A1.