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 2-years-old female infant was referred to the First Affiliated Hospital, Jinan University, due to elevated serum total bile acids (TBA) discovered for 21 months. At the age 3 months, she was admitted to Women and Children's Hospital of Quanzhou because of jaundice for 2 months. Laboratory test revealed that the serum levels of TBA, direct bilirubin (DBIL), aspartate transaminase (AST) and alanine transaminase (ALT) were all elevated (Table ), and she was thus diagnosed to have cholestatic liver disease. After being treated with intravenous reduced glutathione and ademetionine-1,4-butanedisulfonate for 9 days, which were commonly used in cholestatic patients with elevated alanine transaminase levels, her jaundice was alleviated, but the liver function indices remained abnormal (Table ). Then oral ursodesoxycholic acid was given and she was discharged at the age 3.3 months. During the subsequent follow-up over 20 months, she showed normal anthropometric and neurobehavioral development without abnormal appearance, and her cholestasis resolved completely since the age 7 months. However, persistently raised TBA levels were observed on repeated biochemical analyses (Table ). So she was referred to our hospital for further investigation and management when aged 2 years.\nThe patient was the elder sister of two monochorionic diamniotic twins who was delivered by cesarean section at the gestation age of 37 weeks and 2 days with the birth weight 2.25 kg and body length 45.0 cm. Her father is a hepatitis B virus (HBV) carrier who was clinically healthy but with slightly elevated serum TBA level on biochemistry analysis, and her mother was physically and biochemically healthy (Table ). There was no family history of any genetic disease.\nPhysical examination revealed a body weight of 12.0 kg, height 83.5 cm and head circumference 46.0 cm. No jaundice was observed in the skin and sclera. No stridor, crackles or crepitus was heard in the two lungs, and the heart sound was normal without any murmurs. There was no abdominal distention, and the liver and spleen were non-palpable. Physiological reflexes were normal and no pathological reflexes could be found on nervous system examination. On biochemical analysis, the TBA level reached 173.8 μmol/L (0–10 μmol/L) as other indices were normal (Table ).