5118: Prospective Cross-Sectional Non-invasive Assessment of Chronic Liver Disease in Urea Cycle Disorders

Study Summary

The purpose of this study is to measure liver stiffness and chemicals in the blood that test for liver injury and function in three urea cycle disorders.

For Diseases:

• Argininosuccinate Lyase Deficiency (ASLD)
• Arginase 1 Deficiency (ARG1D)
• Ornithine Transcarbamylase Deficiency (OTCD)

Background

Some patients with urea cycle disorders develop long-term liver disease with a buildup of scar tissue in the liver called fibrosis. This scar tissue can cause increased hardening of the liver tissue and cause damage to the liver.

Recently, a new ultrasound test known as shear wave elastography (SWE) has become available. This new ultrasound is able to measure hardening of liver tissue (liver stiffness). The purpose of this study is to measure liver stiffness in patients with three different urea cycle disorders and compare these results to the levels of chemicals in the blood that test for liver injury and function.

The research questions are:

1. To assess liver stiffness in individuals with ASLD, ARG1D, and OTCD.
2. To assess markers of hepatocellular injury, function, and biomarkers for hepatic fibrosis in individuals with ASLD, ARG1D, and OTCD

About this Study

This is a cross-sectional pilot study being conducted at Baylor College of Medicine, Houston, TX; University of California San Francisco (UCSF), San Francisco CA; and Seattle Children’s Hospital, Seattle, WA

There will be only one study visit. At that time, we will:

• Measure your vital signs (Blood pressure, temperature, heart rate, respirations, height and weight
• Review your medical history
• Take some of your blood
• Give you a shear wave elastography ultrasound

Who Can Join

To be eligible to participate, you must:

1. Be between age > 5 years and < 60 years
2. Weight ≥ 11 kg
3. Be a Male or female with a diagnosis of ASLD or ARG1D based on the following:
   1. ASLD:
      • Presence of argininosuccinic acid in blood or urine and/or
      • Decreased AL enzyme activity in cultured skin fibroblasts or other appropriate tissue and/or
      • Identification of pathogenic mutation and/or
      • Hyperammonemia and first degree relative meets at least one of the criteria for AL Deficiency
   2. ARG1D:
      • >5 fold elevated arginine in blood and/or
      • Decreased arginase enzyme level in red blood cells or other appropriate tissue and/or
      • Identification of pathogenic mutation and/or
      • Hyperammonemia and first degree relative meets at least one of the criteria for ARG Deficiency
4. Be a female with a diagnosis of OTCD based on the following:
   • Identification of pathogenic mutation and/or
   • <20% of control OTC activity in liver and/or
   • Elevated urinary orotate (>20 uM/mM creatinine) in a random urine sample or after allopurinol challenge test and/or
   • Hyperammonemia and first degree relative meets at least one of the criteria for OTC Deficiency

You are not eligible to participate if:

• You have a history of hyperammonemia (blood ammonia greater than 100 micromoles/L) documented in the medical record or reported by the patient in the 30 days preceding enrollment visit
• You have a history of liver transplantation
• You are currently pregnant
• You have a confirmed diagnosis of chronic viral hepatitis, autoimmune liver disease, or alcohol liver disease
• You are a Male with OTCD

To Learn More

To learn more about this a study, please contact a participating site.