To explore clinical features, gene detection results, diagnosis and treatment of infant cholestasis (IC) caused by ABCB4 gene mutation and cytomegalovirus (CMV) infection.

A 9-month-old girl was admitted to the outpatient department of the Seventh Affiliated Hospital of Sun Yat-Sen University due to the increase of serum total bile acid (sTBA) for 9 months with no yellow skin, rash, liver and spleen enlargement. The clinical data, including clinical features, outpatient examination results, laboratory findings and gene detection, were retrospectively analyzed. Meanwhile, the relevant literature of children with IC caused by ABCB4 gene mutation in home and abroad databases were searched, and the literatures were reviewed. The procedure followed in the whole study were in accordance with World Medical Association Declaration of Helsinki revised in 2013.

①The girl visited our outpatient department at 9 months old, and the level of sTBA was 410.1 μmol/L. She was G₂P₂, born by delivery at full term, had no abnormal appearance and had no history of " neonatal jaundice" . Two months after birth, she developed dark green skin and sclera with repeated vomiting of milk. She was admitted to the local children′s hospital and was diagnosed as " cholestatic liver disease, cytomegalovirus infection and urinary tract infection" . She was discharged after 2 weeks of treatment with ganciclovir. The bile acid level was 152.8 μmol/L and CMV-DNA was less than 4×10² copies/mL. After discharge, ursodeoxycholic acid capsule, 10 mg/(kg·d), was taken orally. Her dark green color of skin gradually faded and she did not defecate in the shape of clay soil. Her liver function was monitored and sTBA concentration and gamma-glutamyl transpeptidase (GGT) level still higher than normal. ②Laboratory test results in our hospital were as follows. Serum CMV immunoglobulin (Ig) G antibody was positive, CMV IgM antibody was negative, CMV-DNA was less than 55×10² copies/mL and the hepatobiliary ultrasound was normal. Exome sequencing showed that she and her father carried ABCB4 gene variation. She was given oral treatment with ursodeoxycholic acid capsule 10 mg/(kg·d) and glutathione tablet 0.1 g, 3 times per day. sTBA and liver enzymes gradually decreased to the normal range after 18 month of following-up. ③Literature review results were as follows. A total of 8 domestic and foreign literatures about IC caused by ABCB4 gene mutation were retrieved, involving 14 children, who were all diagnosed with progressive familial IC type 3 (PFIC3), accompanied by liver enlargement, elevated sTBA and GGT levels.A total of 20 mutation sites of ABCB4 gene were detected in these children, 9 cases received ursodeoxycholic acid, and 7 cases showed improvement in clinical symptoms and results of laboratory test.

Children with ABCB4 gene mutation complicated with CMV detection can cause IC. As to children with persistent elevated sTBA, abnormal liver enzymes, unclear etiology and poor therapeutic effect, it is recommended to conduct the gene detection to further investigate IC caused by ABCB4 gene abnormality.