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Updated: Feb 26, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Early Diagnosis of ABCB11 Spectrum Liver Disorders by Next Generation Sequencing
Su Jeong Lee1, Jung Eun Kim1, Byung-Ho Choe1
1Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Korea.
Insights
Early diagnosis of ABCB11 spectrum liver disorders, including benign recurrent intrahepatic cholestasis and progressive familial intrahepatic cholestasis, is crucial. Genetic analysis aids in accurate diagnosis and timely treatment, potentially preventing unnecessary liver transplants.
Area of Science:
- Hepatology
- Medical Genetics
- Pediatric Gastroenterology
Background:
- Neonatal cholestasis presents a diagnostic challenge with diverse etiologies.
- ABCB11 spectrum liver disorders, including PFIC and BRIC, often exhibit overlapping clinical features.
- Accurate diagnosis is essential for appropriate management and prognosis.
Purpose of the Study:
- To achieve early diagnosis of ABCB11 spectrum liver disorders.
- To differentiate between benign recurrent intrahepatic cholestasis and progressive familial intrahepatic cholestasis.
- To evaluate the role of genetic analysis in managing neonatal cholestasis.
Main Methods:
- Fifty patients with neonatal cholestasis underwent etiological evaluation.
- Genetic analysis, including whole exome and Sanger sequencing, was performed on suspected cases.
- Two families with confirmed ABCB11 spectrum liver disorders received genetic counseling.
Main Results:
- Idiopathic/viral hepatitis (34%) and metabolic diseases (20%) were common causes of neonatal cholestasis.
- Novel ABCB11 mutations were identified in patients with PFIC and atypical BRIC.
- Genetic confirmation enabled timely liver transplantation for PFIC and prevented unnecessary transplantation for BRIC.
Conclusions:
- ABCB11 spectrum liver disorders present with indistinguishable clinical signs during acute episodes.
- Comprehensive genetic analysis is vital for accurate diagnosis and effective treatment strategies.
- Genetic insights guide therapeutic decisions, optimizing patient outcomes.
Purpose:
The goal of this study was the early diagnosis of ABCB11 spectrum liver disorders, especially those focused on benign recurrent intrahepatic cholestasis and progressive familial intrahepatic cholestasis.
Methods:
Fifty patients presenting neonatal cholestasis were evaluated to identify underlying etiologies. Genetic analysis was performed on patients suspected to have syndromic diseases or ABCB11 spectrum liver disorders. Two families with proven ABCB11 spectrum liver disorders were subjected to genetic analyses to confirm the diagnosis and were provided genetic counseling. Whole exome sequencing and Sanger sequencing were performed on the patients and the family members.
Results:
Idiopathic or viral hepatitis was diagnosed in 34%, metabolic disease in 20%, total parenteral nutrition induced cholestasis in 16%, extrahepatic biliary atresia in 14%, genetic disease in 10%, neonatal lupus in 2%, congenital syphilis in 2%, and choledochal cyst in 2% of the patients. The patient with progressive familial intrahepatic cholestasis had novel heterozygous mutations of ABCB11 c.11C>G (p.Ser4*) and c.1543A>G (p.Asn515Asp). The patient with benign recurrent intrahepatic cholestasis had homozygous mutations of ABCB11 c.1331T>C (p.Val444Ala) and heterozygous, c.3084A>G (p.Ala1028Ala). Genetic confirmation of ABCB11 spectrum liver disorder led to early liver transplantation in the progressive familial intrahepatic cholestasis patient. In addition, the atypically severe benign recurrent intrahepatic cholestasis patient was able to avoid unnecessary liver transplantation after genetic analysis.
Conclusion:
ABCB11 spectrum liver disorders can be clinically indistinguishable as they share similar characteristics related to acute episodes. A comprehensive genetic analysis will facilitate optimal diagnosis and treatment.
