CASE
A 2 months and 28 days old male, Han Nationality from the Jianshui County of Yunnan Province, was born full term at 38.5 weeks gestation with a birth weight of 3,200 g and a birth length 47 cm, who was not the product of a consanguineous marriage. He presented skin yellowing, mild anemia and feeding difficulty for 2 months. Physical examination revealed a body weight of 6.5 kg, height 58 cm and head circumference 41.5 cm. Obvious jaundice was observed in the skin and sclera. No stridor, crackles or crepitus was heard in the two lungs. There was no abdominal distention, liver was palpable under the right costal margin (2.0 cm), spleen was non-palpable. Echocardiography showed patent foramen ovale (PFO). Laboratory test revealed that the serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total bile acids (TBA), aspartate transaminase (AST) and alanine transaminase (ALT), thyroid stimulating hormone (TSH), and alkaline phosphatase (ALP) were all elevated; 25-hydroxy vitamin D (VD) was decreased (Table 1). Blood routine examination revealed that the mean corpuscular volume (MCV), corpuscular hemoglobin (MCH) and hemoglobin (HB) were decreased (Table 1). The baby was diagnosed to have hypercholesterolemia, hyperbilirubinemia, mild anemia, abnormal liver and thyroid function, and high suspicion of NTCPD. Sanger sequencing revealed that the patient was a compound heterozygous for the c.800C>T (p.Ser267Phe) and c.263T>C (p.lle88Thr) SLC10A1 mutations, which was inherited from the mother and father, respectively (Figures 1A-F); moreover, the patient and his mother were both heterozygous missense mutation of c.2698G>A (p.Ala900Thr) in AT-rich interaction domain 1A (ARID1A) gene (Figure 1G and H), and heterozygous deletion type α- Thalassemia (–SEA/αα), while his father was normal (Figure 1I). A diagnosis of NTCPD with heterozygous missense mutations in c.800C>T and c.263T>C, ARID1A gene with a heterozygous missense mutation in c.2698G>A, and heterozygous deletion type α- Thalassemia (–SEA/αα) was confirmed. Considering that the genotype of ARID1A is related to the phenotype of CSS, we did a detailed physical examination for the child again. However, except for feeding difficulties and PFO, we did not find any typical characteristics of CSS, such as developmental delay (DD), mental retardation, hypo/aplasia of the fifth digit phalanges/nails, coarse facial features, or body hypertrichosis and so on, which may be due to the baby was too young. The baby was started on symptomatic and supportive treatment including phototherapy for neonatal indirect hyperbilirubinemia, intravenous ademetionine1,4-butanedisulfonate, oral ursodeoxycholic acid capsules, fat-solublevitamin D and clostridium butyricum powder. His transaminase, bilirubin, TSH, ALP, VD and foramen ovale gradually returned to normal, but the levels of TBA remained high, and mild anemia, which could only be continuously observed. After two years of close clinic follow-up, the baby grew well and had no other special clinical signs except mild hyperbilirubinemia and anemia (Table1, Figure 1J). We will continue to follow up and observe the patient. Written informed consent was obtained from the child’s parents.