ABCB4 Deficiency Presenting as a Pruritus-Free Continuous Spectrum From Childhood Cholestasis to Adult Cirrhosis: A Case Report.
- 1Department of Infectious Diseases/Hepatology The Second People's Hospital of Gansu Province Lanzhou China.
- 2Department of Healthcare-Associated Infection Management The Second People's Hospital of Gansu Province Lanzhou China.
Abstract
Progressive familial intrahepatic cholestasis type 3 (PFIC3) is caused by biallelic mutations in the ABCB4 gene and typically presents in childhood. However, the full phenotypic spectrum-particularly adult-onset and pruritus-free forms-remains under-recognized. We report the case of a 28-year-old male who presented with pruritus-free decompensated cirrhosis after a 10-year diagnostic delay. Genetic testing revealed compound heterozygous ABCB4 variants [c.249C>A (p.Asp83Glu) and c.1466A>G (p.Asn489Ser)], which were initially classified as variants of uncertain significance (VUS). Proactive family screening identified his asymptomatic 14-year-old sister, who carried the same genotype and exhibited significant gamma-glutamyl transferase (GGT) elevation (142.1 U/L) but no pruritus. Perfect genotype-phenotype cosegregation in the two siblings, combined with the absence of these variants in population databases (PM2 and PP1 criteria per American College of Medical Genetics and Genomics [ACMG] guidelines), provided decisive evidence for reclassifying the VUS as "Likely Pathogenic." This family defines a pruritus-free continuous PFIC3 spectrum and demonstrates that systematic screening of all first-degree relatives upon proband diagnosis is essential for enabling pre-symptomatic intervention. The key learning point is that ABCB4 deficiency should be considered in adults with cryptogenic cirrhosis even without pruritus, and family screening can resolve diagnostic uncertainty while facilitating early therapy.
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BibTeX
@article{ma2026abcb4,
title = {{ABCB4 Deficiency Presenting as a Pruritus-Free Continuous Spectrum From Childhood Cholestasis to Adult Cirrhosis: A Case Report.}},
author = {Rongxia Ma and Wenjie Zhang and Xiaojuan Yang and Haojun Zhang},
journal = {Clinical case reports},
year = {2026},
month = nov,
doi = {10.1002/ccr3.73455},
url = {https://europepmc.org/article/MED/42996793},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - ABCB4 Deficiency Presenting as a Pruritus-Free Continuous Spectrum From Childhood Cholestasis to Adult Cirrhosis: A Case Report.
AU - Rongxia Ma
AU - Wenjie Zhang
AU - Xiaojuan Yang
AU - Haojun Zhang
PY - 2026
DA - 2026/11/05
JO - Clinical case reports
DO - 10.1002/ccr3.73455
UR - https://europepmc.org/article/MED/42996793
AB - Progressive familial intrahepatic cholestasis type 3 (PFIC3) is caused by biallelic mutations in the ABCB4 gene and typically presents in childhood. However, the full phenotypic spectrum-particularly adult-onset and pruritus-free forms-remains under-recognized. We report the case of a 28-year-old male who presented with pruritus-free decompensated cirrhosis after a 10-year diagnostic delay. Genetic testing revealed compound heterozygous ABCB4 variants [c.249C>A (p.Asp83Glu) and c.1466A>G (p.Asn489Ser)], which were initially classified as variants of uncertain significance (VUS). Proactive family screening identified his asymptomatic 14-year-old sister, who carried the same genotype and exhibited significant gamma-glutamyl transferase (GGT) elevation (142.1 U/L) but no pruritus. Perfect genotype-phenotype cosegregation in the two siblings, combined with the absence of these variants in population databases (PM2 and PP1 criteria per American College of Medical Genetics and Genomics [ACMG] guidelines), provided decisive evidence for reclassifying the VUS as "Likely Pathogenic." This family defines a pruritus-free continuous PFIC3 spectrum and demonstrates that systematic screening of all first-degree relatives upon proband diagnosis is essential for enabling pre-symptomatic intervention. The key learning point is that ABCB4 deficiency should be considered in adults with cryptogenic cirrhosis even without pruritus, and family screening can resolve diagnostic uncertainty while facilitating early therapy.
SN - 2050-0904
ER -