Hepatic Histopathology in Urea Cycle Disorders

This is a multi-site, retrospective chart review as well as a prospective study to evaluate histopathologic findings in liver samples from individuals with any UCD diagnosis. This study will be conducted at all Urea Cycle Disorders Consortium (UCDC) sites: Baylor College of Medicine in Houston, TX and Children's National Medical Center in Washington D.C.

Study Overview

• Status: Recruiting
• Conditions: Ornithine Transcarbamylase Deficiency; Urea Cycle Disorder; Carbamyl Phosphate Synthetase Deficiency; Argininosuccinic Aciduria; Hyperargininemia; Citrullinemia 1; ARGI Deficiency; ASL Deficiency; ASS Deficiency; NAGS Deficiency

Detailed Description

Urea cycle disorders (UCDs) are among the most common inborn errors of liver metabolism. With early diagnosis and improved treatments, the survival of individuals with UCDs has improved, and this improved survival has led to unmasking of some long-term complications such as hepatic dysfunction and progressive fibrosis in a subset of patients. Hepatic complications in UCDs are quite variable and dependent upon the specific metabolic defect.

• Study Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

• Study Contact: Name: Saima Ali, MSN; Phone Number: 832-822-4183; Email: saima.ali@bcm.edu

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Not yet recruiting
      • Children's National Medical Center
      • Contact: Kara Simpson, MS, CGC; Phone Number: 202-476-6216; Email: ksimpson@childrensnational.org
      • Principal Investigator: Nicholas A Mew, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Texas Children's Hospital
      • Contact: Saima Ali, MSN; Phone Number: 832-822-4183; Email: sma1@bcm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals with urea cycle disorders

Description

Inclusion Criteria:

• Diagnosis of primary urea cycle disorder based on clinical suspicion confirmed by enzyme activity, DNA testing or metabolite analysis.
• History of liver transplantation and/or liver biopsy OR
• Planned liver transplantation and/or liver biopsy

Exclusion Criteria:

• Unavailability of histopathology report from the liver biopsy or explant, or unavailability of liver tissue or slides from the biopsy or explant OR
• Anticipated inability to obtain pathology report, liver disease, tissue blocks, or pathology slides after liver biopsy or transplantation
• Known history of a secondary cause for liver disease such as chronic viral hepatitis, autoimmune liver disease, short gut, small bowel syndrome, alcohol liver disease, or TPN-related cholestatic disease

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic fibrosis	Staging of fibrosis from histopathology report from the liver biopsy or explant	Day 1
Steatosis	Grade of steatosis from histopathology report from the liver biopsy or explant	Day 1
Hepatic glycogenosis	Presence and type of glycogenosis from histopathology report from the liver biopsy or explant	Day 1

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: Children's National Research Institute
• Investigators: Principal Investigator: Lindsay Burrage, MD, PhD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2022
• Primary Completion (Anticipated): June 30, 2025
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): June 1, 2021

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Histopathology; Liver biopsy; Liver disease; Liver transplant
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Mitochondrial Diseases; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Ornithine Carbamoyltransferase Deficiency Disease; Urea Cycle Disorders, Inborn; Carbamoyl-Phosphate Synthase I Deficiency Disease; Citrullinemia; Argininosuccinic Aciduria; Hyperargininemia
• Other Study ID Numbers: H-51257

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No