PEARL - Pediatric Evaluation and Registry for Liver Cholestasis in Canada
The purpose of this study is to create a national, multi-centre registry for children with Alagille syndrome (ALGS) and Genetic Intrahepatic Cholestasis (GIC) that follows participants long-term, ensuring standardized, high-quality data capture across all participating pediatric hepatology centres. Inclusion criteria: • Pediatric participants (\<18 years old) with genetically confirmed or clinically diagnosed ALGS or any of the various subtypes of GIC, each associated with a distinct genetic mutation: A. PFIC Type 1 (FIC1 Deficiency) - Mutation in ATP8B1 gene. B. PFIC Type 2 (BSEP Deficiency) - Mutation in ABCB11 gene. C. PFIC Type 3 (MDR3 Deficiency) - Mutation in ABCB4 gene. D. PFIC Type 4 (TJP2 Deficiency) - Mutation in TJP2 gene. E. PFIC Type 5 (FXR Deficiency) - Mutation in NR1H4 gene. F. PFIC Type 6 (MYO5B-Associated) - Mutation in MYO5B gene. G. Progressive cholestasis of northwestern Quebec (PCNQ)-Mutation in UTP4 gene. * Enrollment within Canadian pediatric liver centers participating in the registry. * Written informed consent obtained from participant if they have the capacity, or parents/guardians, and assent from participants as appropriate. Exclusion criteria: • Inability to comply with follow-up requirements (lost to follow-up). Participants will be recruited from our hepatology clinics retrospectively (diagnosed on or after January 1, 2022) and prospectively (newly diagnosed). Written consent/assent will be obtained from all participants prior to data collection from the participants' medical chart.
• Pediatric participants (\<18 years old) with genetically confirmed or clinically diagnosed ALGS or any of the various subtypes of GIC, each associated with a distinct genetic mutation:
⁃ A. PFIC Type 1 (FIC1 Deficiency) - Mutation in ATP8B1 gene. B. PFIC Type 2 (BSEP Deficiency) - Mutation in ABCB11 gene. C. PFIC Type 3 (MDR3 Deficiency) - Mutation in ABCB4 gene. D. PFIC Type 4 (TJP2 Deficiency) - Mutation in TJP2 gene. E. PFIC Type 5 (FXR Deficiency) - Mutation in NR1H4 gene. F. PFIC Type 6 (MYO5B-Associated) - Mutation in MYO5B gene. G. Progressive cholestasis of northwestern Quebec (PCNQ)-Mutation in UTP4 gene. Other novel PFIC-like conditions continue to be identified and may be included in the registry. If additional conditions are identified for inclusion in the registry, a protocol amendment will be submitted for REB approval.
• Enrollment within Canadian pediatric liver centers participating in the registry. These include: Children's Hospital of Eastern Ontario (Ottawa, ON, Lead Site), CHU Sainte-Justine (Montreal, QC), McMaster Children's Hospital (Hamilton, ON), Montreal Children's Hospital (Montreal, QC), Alberta Children's Hospital (Calgary, AB), Stollery Children's Hospital (Edmonton, AB), Janeway Children's Health and Rehabilitation Centre (St. John's, NL), Jim Pattison Children's Hospital (Saskatoon, SK), Children's Hospital LHSC (London, ON), Children's Hospital IWK Health Centre (Halifax, NS), BC Children's Hospital (Vancouver, BC), HSC Winnipeg Children's Hospital (Winnipeg, MB), Hôpital de l'Enfant-Jésus (Quebec City, QC)
• Written informed consent obtained from participant if they have the capacity, or parents/guardians, and assent from participants as appropriate.