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5117: Comparative effectiveness of therapy in rare diseases: Liver transplantation vs. conservative management of urea cycle disorders


This study will compare the outcomes of liver transplantation vs. conservative medical treatment in patients with UCD for survival, neurocognitive development, and quality of life.

For Diseases

  • Carbamyl Phosphate Synthetase (CPS) Deficiency
  • Ornithine Transcarbamylase (OTC) Deficiency
  • Argininosuccinate Synthetase Deficiency (Citrullinemia I)
  • Argininosuccinate Lyase Deficiency (Argininosuccinic Aciduria)


Urea cycle disorders (UCD) are genetic disorders caused by the liver's inability to breakdown ammonia from proteins; ammonia then accumulates and is toxic to the brain. UCD cause brain damage and intellectual and developmental disabilities and even death. Medical treatment involves special diet low in protein, drugs that help metabolize ammonia and amino acid supplements (conservative management). However, many patients and families choose liver transplantation rather than conservative treatment; both alternatives are effective in reducing or normalizing blood ammonia. While liver transplantation eliminates the ammonia problem, conservative management does so only temporarily and in many patients, blood ammonia can rise during an infection or other stress.

About this Study

The long-term objective of this study is to help patients make decisions about management alternatives (conservative vs. liver transplantation) by providing them with scientific information that is currently lacking. The questions that will be addressed are:

  1. What is the disease's risk of mortality and illness in each treatment approach?
  2. What can parents expect in terms of neurocognitive development of their child and his/her school performance?
  3. What are the expected effects of each treatment on short-term and long-term quality of life?
  4. What factors do patients' primary caretakers (typically parents) consider when making a decision to pursue liver transplantation or continue conservative management for their child with UCD?

The study will involve up to about 185 participants

Participants with UCD will undergo the following:

  • review of medical records
  • discussion of medical history
  • completion of quality of life questionnaires
  • Neuropsychological testing

Caregivers will participate in interviews and focus groups

Health care providers will participate in interviews.

Target Enrollment

Children with UCD:

  • Age 18 and under
  • Diagnosed with the following Neonatal-type urea cycle disorders: CPSD, OTCD, ASD (Citrullinemia) or ALD (argininosuccinic aciduria)
  • Willing to participate in at least one neuropsychological assessment and one quality of life assessment
  • Permit access to medical records and medical providers


  • must be a primary caretaker of a patient age 18 and under who has been diagnosed with either CPSD, OTCD, ASD or ALD
  • must have considered, are currently considering, or opted for, liver transplantation as a treatment for UCD.
  • Willing to participate in a 60 minute semi-structured interview and/or a 60-90 minute focus group discussion

Health care providers:

  • must be either a metabolic disease physician, liver transplant surgeon, gastroenterologist, genetic counselor, or nurse or other professional that participates in treating patients diagnosed with either CPSD, OTCD, ASD or ALD
  • be willing to participate in a 60 minute semi-structured interview

To Learn More

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