Summary
We are doing the study to see how having certain disorders of protein metabolism affects thinking, biochemistry and the structure of the brain. We will be using MRI to study the structure of the brain. We will also study the amount of certain chemicals in the brain. We will use behavioral testing to look at your thinking skills while you are in the MRI machine. There will be three separate groups that we study and the inclusion criteria are summarized below. We will also ask for healthy people to join the study to see how the brains of people with urea cycle disorders differ from healthy people.
For Diseases
This study is for all urea cycle disorders.
This study has 3 different sections:
- People with ornithine transcarbamylase deficiency (OTC) will be in group 1
- People with argininosuccinate synthase deficiency (ASSD) or argininosuccinate lyase deficiency (ASLD) will be in group 3
- People with all other urea cycle disorders will be in group 2
Background
Metabolism is the process by which your body extracts energy from food. Urea cycle disorders represent a group of rare errors of metabolism that lead to the build-up of ammonia in your body because enzymes needed to properly metabolize protein are defective or non functional. Ammonia is a toxic product of protein metabolism that builds up in people who have a urea cycle disorder due to the lack of the enzymes. Individuals with urea cycle disorders cannot get rid of the ammonia that accumulates in their body and the ammonia can build up in the brain and cause problems with thinking and movement. The symptoms of Urea Cycle disorders may appear at any time including birth, childhood or adulthood.
About this Study
This study is longitudinal (which means it is observational and we collecting information over a period of time). Depending upon which group you are in, you will have a baseline and follow up scan.
For group 1, you will have a baseline MRI scan and a follow up MRI scan two years later.
For group 2, you will have follow up MRI scans at one week, one month, 6 months and one year after a hyperammonemic episode.
For group 3 you will have a baseline MRI scan and a follow up MRI scan in one year. In addition to having and MRI scan, you will also be asked to complete some educational testing outside of the scanner.
Target Enrollment
To be eligible to participate, you must be an individual with the following:
- Inclusion criteria for group 1:
- Confirmed diagnosis of ornithine transcarbamylase deficiency (OTCD) by genetic analysis (genotype) and/or enzyme analysis with at least a single episode of hyperammonemic (HA) encephalopathy
- Ability to undergo MRI without sedation
- Ages 7 – 30 years
- Ability to provide informed consent or assent to the procedures
- Healthy controls (age and gender matched)
- Inclusion criteria for group 2:
- Males and females with a UCD who are having an acute metabolic crisis, with ammonia levels between 100-300 µM
- Subjects must be awake, and not comatose and able to maintain patent airway on their own and in the opinion of the examining physician, medically stable without risk for acute decompensation and must continue to be stable based on visual contact, vital sign measurement and voice contact with subjects while in the scanner
- Age range 7-30 years
- Able to undergo neuroimaging safely (i.e. without ferromagnetic devices)
- Sexually active female of childbearing potential must agree to urine pregnancy test
- Admitted to the hospital for treatment of HA at one of the 4 sites for this study
- Can be subjects who were originally enrolled in aim 1 who then have HA (they will cross over to aim 2)
- Inclusion criteria for group 3
- Confirmed diagnosis of arginosuccinate ASSD, and ASLD by genotype and/or enzyme analysis or healthy age and gender matched control
- Ability to undergo MRI without sedation
- Age 7 – 30 years
- Able to provide informed consent or assent to the procedures
You are not eligible to participate if you have:
- Exclusion Criteria for group 1:
- Inability to undergo MRI without sedation
- Metal implants, including orthodontic braces
- Other health conditions contra-indicated in MRI
- Medically unstable at time of scheduled research visit
- Unable to provide informed consent or assent to the procedures
- Exclusion criteria for group 2:
- Ammonia level > 300 µM, or <100 µM
- Presence of coma and/or inability to maintain a patent airway
- Age younger than 7 or older than 30 years
- Subject with ferromagnetic device that precludes safe MRI imaging
- Pregnant female
- Unstable medically, at risk for decompensations
- Combative, or severely neurologically compromised irrespective of ammonia level and showing declining medical status in the scanner based on visual, voice contact and electronic HR monitoring.
- Subjects must be awake, and not comatose and able to maintain patent airway on their own
- Exclusion criteria for group 3:
- Inability to undergo MRI without sedation
- Metal implants, including orthodontic braces
- Other health conditions contra-indicated for MRI
- Medically unstable at time of scheduled research visit
- Unable to provide informed consent or assent
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 to the right to inquire about participation.