The purpose of this study is to measure liver stiffness and chemicals in the blood that test liver injury and function in four urea cycle disorders.
Sometimes the seizures are not clinically obvious, but can be picked up if a video recording and concurrent EEG (video EEG is used, cVEEG). cVEEG is used in many intensive care units across the country to pick up seizures. We want to determine if having seizures due to HA leads to any adverse cognitive outcomes, and want to use the EEG to identify any changes that may be associated with that.
This study is for four urea cycle disorders to include:
- argininosuccinate synthetase deficiency (ASS1D)
- argininosuccinate lyase deficiency (ASLD)
- arginase deficiency (ARG1D)
- ornithine transcarbamylase deficiency (OTCD)
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, new biomarkers for liver fibrosis have been introduced. Some of these biomarkers are measured in blood. In addition, new radiologic methods, including FibroScan® and magnetic resonance elastography (MRE) have been introduced. These new imaging methods are able to measure hardening of liver tissue (liver stiffness).
About this Study
There are two parts to this research study.
In the first part of the study, you will be asked to sign the informed consent form. You will be asked questions about your medical history and current medications you are taking. You will have your blood drawn. A urine for pregnancy test will be collected if you are a female of childbearing age. A FibroScan® will be performed. The first part of the study should be completed in one outpatient visit.
If you qualify for second part of the study, you will be called to return to the hospital or research center for a Magnetic Resonance Elastography (MRE) within the one year of your first visit. The procedure will take around 30 minutes.
To be eligible to participate, the following criteria must be met:
- Inclusion criteria for First Part of Study:
- Age 6 years and < 65 years
- Weight ≥ 11 kg
- Molecular or biochemical diagnosis of argininosuccinate synthetase deficiency (ASS1D), argininosuccinate lyase deficiency (ASLD), arginase deficiency (ARG1D), or ornithine transcarbamylase deficiency (OTCD)
- Exclusion Criteria for First Part of Study:
- Prior liver transplantation
- Episode of acute hyperammonemia (ammonia ≥ 100 umol/L) in the 30 days prior to enrollment
- Confirmed diagnosis of chronic viral hepatitis, short gut, small bowel syndrome, autoimmune liver disease, alcohol liver disease, TPN requirement, or TPN-related cholestatic disease
- Adults with BMI ≥ 45 kg/m2
- Current pregnancy
- Open wound near expected Fibroscan® probe application site
- Use of implantable active medical device such as cardiac pacemaker or implantable cardioverter-defibrillator
- Inclusion criteria for Second Part of Study:
- Participation in First Part of this study
- Exclusion Criteria for Second Part of Study:
- Individuals with claustrophobia or other inability to complete study procedures
- Known diagnosis of hemochromatosis
- Presence of implants or devices incompatible with MRI
- Inability to breath-hold for 20 seconds for the elastography sequence
- Current pregnancy
- Confirmed diagnosis of chronic viral hepatitis, autoimmune liver disease, short gut, small bowel syndrome, alcohol liver disease, TPN requirement, or TPN-related cholestatic disease
- Episode of documented acute hyperammonemia (ammonia > 100 umol/L) in the 30 days prior to scheduled visit for Second Part of study
How to participate
In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation.
Baylor College of Medicine/Texas Children’s Hospital
Saima Ali, FNP-C
Children's Hospital Colorado
Children's Hospital of Philadelphia
Children's National Hospital
Kara L. Simpson, MS, CGC
Seattle Children's Hospital