Patient 1 was a 5–year-and-11-month-old female referred to the First Affiliated Hospital, Jinan University due to abnormal liver function discovered for 5 years and 7 months. When aged 4 months, she was admitted to a hospital in Guangzhou due to jaundice for 3 months, where physical examination revealed an enlarged liver 4.0 cm below the right costal margin, and a liver function test revealed elevated serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP), indicating cholestatic jaundice (). Blood amino acid spectrum analysis by tandem mass spectrometry (MS-MS) revealed raised citrulline, methionine, arginine, and threonine, while large quantities of galactose, galactitol, galactonate, and 4-hydroxyphenyllactate (4HPL) were detected on urinary gas chromatography-mass spectrometry (GC-MS) analysis. Considering the above clinical and laboratory findings, NICCD was suspected, and breast-feeding was stopped while a lactose-free and medium-chain triglycerides (MCT)-enriched formula was introduced. When aged 4.9 months, SLC25A13 genetic analysis in our hospital unveiled a homozygote of the c.852_855del4 mutation () and the diagnosis of NICCD was hence made. Thereafter, besides feeding with the therapeutic formula, supplemental foods rich in protein were encouraged. As a result, her liver function indices got improved gradually and returned to normal by age 10.2 months. However, the hypercholanemia was refractory, with total bile acid (TBA) levels fluctuating from 27.6 µmol/L to 340.2 µmol/L (reference range: 0–10 µmol/L) (). After the age 2 years, the patient showed a fondness for foods rich in protein and fat while an aversion to carbohydrate-rich diets.\nAs the first product of a non-consanguineous couple, the child was delivered spontaneously at the gestational age of 38 weeks and 3 days after an uneventful pregnancy, with a birth weight of 3.0 kg and body length 50 cm. The parents were healthy, and there was no family history of any genetic or infectious diseases.\nPhysical examination revealed a body temperature (T) 36.5°C, heart rate (HR) 115 beats/min (bpm), respiratory rate (RR) 20 bpm, weight (WT) 18 kg, height 107.0 cm. No jaundice was observed in the skin and sclera. The lungs were clear. No murmurs or abnormal heart sounds were heard. There was no abdominal distention, and the liver and spleen were not enlarged. Physiological reflexes were normal and no pathological reflexes could be found on nervous system examination. The extremities were warm, and the distal perfusion was excellent.\nLaboratory investigation showed otherwise normal biochemical indices but a TBA level of 48.7 µmol/L. In view of the intractable hypercholanemia, NTCP deficiency was highly suspected, and SLC10A1 genetic analysis was performed. As a result, the patient was a homozygote, while the parents, carriers, of the reportedly pathogenic variant c.800C > T(p.Ser267Phe)(). NTCP deficiency was thus definitely diagnosed. No specific therapy was given but close clinic follow-up was underway.
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.