Patient 2 was a 1-year-and-1-month-old male visiting our clinic due to hypercholanemia discovered for 11 months. At the age 2 months, he was referred to a local hospital because of prolonged jaundice for about 1 month. On biochemistry analysis, elevated serum levels of AST, GGT, ALP, TBIL, DBIL, and IBIL, together with decreased level of albumin were detected, and notably, the TBA level reached 268.7 µmol/L (). Subsequent urinary GC-MS analysis detected elevated 4-hydroxyphenylpyruvate (4-HPPV) and 4HPL, while raised levels of citrulline, methionine, and threonine were detected on MS-MS analysis of blood sample. When aged 2.1 months, the infant undertook SLC25A13 analysis in our hospital, and proved to be a homozygote of the c.852_855del4 mutation (), and the diagnosis of NICCD was thus made. Then breast-feeding was stopped and a lactose-free and MCT-enriched formula was given. Then his jaundice disappeared rapidly, and serum bilirubin levels returned to normal at his age 5.5 months (). However, the hypercholanemia persisted, even beyond 1 year of age (). No steatorrhea or acholic stool was observed during the course of the disease.\nAs the first child of a non-consanguineous couple, the patient was delivered vaginally at the gestational age of 37 weeks and 4 days with the birth weight 2700 g. The Apgar score was 9 points at 1 min and 10 points at 5 min after umbilical ligation. Parents were both hepatitis B virus (HBV) carriers, who were apparently healthy but with slightly raised serum TBA levels (). Family history of any genetic diseases was denied.\nPhysical examination revealed a body T 36.6°C, weight 10.5 kg, HR 126 bpm, and RR 32 bpm. No jaundiced skin and sclera was observed. On auscultation, no abnormal sounds were heard on the lungs and heart. There was no abdominal distention, and the liver and spleen were non-palpable. Primitive reflexes were normal and pathological reﬂexes could not be found on nervous system examination.\nLaboratory test at visiting revealed a serum TBA level of 234.5 µmol/L and otherwise normal indices. SLC10A1 genetic analysis demonstrated that the patient was a homozygote, and his parents, carriers, of the variant c.800C > T (p.Ser267Phe) (). The diagnosis of NTCP deficiency was thus made. No specific therapy was given but clinic follow up was suggested. His serum TBA level was 148 µmol/L () when aged 1 year and 6 months, and a fondness for low-carbohydrate and high-protein foods was noticed since the age of 1 year.
Patient 2. A 5-day-old male infant was admitted to our Neonatal Section because of jaundice for 3 days. Mild jaundice appeared at age 2 days. At the 5th day after birth, the total bilirubin increased to 310.1 μmol/L. Then the infant was referred to our clinic, where a laboratory test revealed elevated TBA as well as indirect hyperbilirubinemia (Table ), and thus the infant was admitted for further management. As the first child of a non-consanguineous couple, the patient was delivered vaginally at the gestational age of 37 weeks with the birth weight 3050 g. The parents were both healthy. Family history of any genetic disease was denied.\nOn physical examination, the body weight was 2910 g, with T 36.2°C, HR 130 beats/min, and RR 43 breaths/min. Jaundiced skin and sclera were observed. The lungs were clear on auscultation, and no abnormal heart sound or murmur was heard. There was no abdominal distention, and the liver and spleen were not palpable. Primitive reflexes were normal and no pathological reflexes could be found on nervous system examination.\nThe patient underwent phototherapy for 3 days. As a result, his jaundice subsided, and he was discharged at age 9 days. No special treatment was given thereafter, and the jaundice did not reappear. However, his serum TBA levels kept high in the following 1 month, and hence SLC10A1 analysis was performed at age 33 days to evaluate the possibility of NTCP deficiency. On Sanger sequencing of the UGT1A1 gene, no pathogenic variant was detected but three benign SNPs in the 3ʹ UTR, i.e. rs10929303, rs1042640 and rs8330 [].