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 1. A 9-day-old female infant was admitted to the Neonatal Section of our Department of Pediatrics due to jaundice over 6 days. At her age of 3 days, jaundiced skin and sclera was noticed, which was then aggravated progressively. As the second product of a non-consanguineous couple, the infant was spontaneously delivered at the gestation age of 38 weeks and 2 days, with a birth weight of 2.85 kg and a body length 48 cm. The Apgar score was 9 points at 1 min after umbilical ligation, and 10 points at 5 min, while the amniotic fluid was clear. The patient had a 9-year-old brother, who was physically healthy with normal social performance. The parents were healthy, and there was not family history of any genetic disease.\nPhysical examination found a body temperature (T) 36.5°C, heart rate (HR) 140 beats/min , respiratory rate (RR) 45 breaths/min, and a body weight (WT) 2940 g. Jaundice was observed in the skin and sclera. The anterior fontanelle was flat and soft, and no malformation of the head, ears, nose, mouth, and eyes could be observed. No positive signs were found in the two lungs and the heart. Her liver and spleen were not enlarged. The extremities were warm, and the distal perfusion was excellent.\nAfter admission, the liver function test revealed indirect hyperbilirubinemia and markedly elevated serum TBA level. Her jaundice was alleviated soon in a response to phototherapy, but the TBA elevation persisted, even on the following-up in the clinic after she was discharged at the age of 19 days (Table ). When aged 25 days, the infant underwent SLC10A1 analysis to evaluate the possibility of NTCP deficiency. Sanger sequencing of the UGT1A1 gene was performed (), but no pathogenic variant was detected.