Abstract
BACKGROUND: In recent years, the number of pediatric patients with unexplained liver disease has been increasing. Whole-exome sequencing (WES) technology has played a significant role in the diagnosis; however, related studies remain limited. AIM: To investigate the clinical characteristics and genetic causes of unexplained pediatric liver disease to improve the diagnosis and treatment of this disease. METHODS: Eighty children with unexplained liver disease were divided into two groups: The liver enzyme elevation group (Group A) and the cholestasis group (Group B). Children with both elevated liver enzymes and cholestasis were assigned to Group B. The clinical characteristics of the patients were retrospectively summarized, and WES was performed in the patients and their parents. RESULTS: Genetic results were obtained in 46 patients (46/80, 57.5%), including 38 in Group A (38/65, 58.5%) and 8 in Group B (8/15, 53.3%). A total of 53 pathogenic or likely pathogenic variants were identified in 42 patients (42/80, 52.5%), including 40 previously reported variants and 13 novel variants. Seven variants of uncertain significance were identified in 7 patients (7/80, 8.8%), of which 4 were novel variants. A total of 19 gene mutations were identified: 2 cases of AGL, 15 cases of ATP7B, 1 case of CAPN3, 4 cases of DMD, 1 case of FLG, 1 case of G6PC, 5 cases of JAG1, 2 cases of PHKA2, 2 cases of PYGL, 1 case of SMARCAL1, 1 case of SMPD1, 1 case of TNFAIP3, 1 case of GLB1, and 1 case of MAT1A in Group A; and 1 case of SLC25A13, 3 cases of JAG1, 1 case of ATP8B1, 1 case of ABCC2, 1 case of ABCD3, and 1 case of 45X in Group B. CONCLUSION: WES significantly improved the etiological diagnosis of unexplained pediatric liver disease, helping guide individualized treatment and improve prognosis.