This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT Urea cycle disorders (UCD) are a group of rare inborn errors of metabolism that commonly present in childhood with episodes of vomiting lethargy and coma. Symptoms are the result of an accumulation of ammonia, a toxic product of protein degradation, which is not adequately metabolized in the liver of affected individuals due to an enzyme deficiency present from birth. Deficiencies in each of the 8 enzymes and transporters that comprise the urea cycle have been identified in patients and all are inherited as recessive traits except for the most common disorder, ornithine transcarbamylase deficiency, which is inherited as an X-linked trait. The risk of death or severe disability from these disorders approaches 50%, and current therapy is considered inadequate. The purpose of this study is to perform a long-term follow-up of a large group of patients with the various urea cycle disorders. We will asess biochemical status, growth and various urea cycle disorders. We will evaluate survival and cognitive outcome of the two most commonly used forms of treatment, alternate pathway therapy and liver transplantation. We will also seek to identify biochemical changes (biomarkers) that may predice future metabolic imbalances so that they can be corrected before clinical symptoms develop. The overall goal of this study is to improve treatment and outcome of this devastating group of disorders. The Office of Rare Diseases (ORD) of the National Institutes of Health (NIH) established a Rare Diseases Clinical Research Network (RDCRN) together with the National Center for Research Resources (NCRR)/General Clinical Research Consortium (GCRC) Program and in collaboration with other NIH Institutes funded ten rare diseases clinical research consortia and one Data and Technology Coordinating Center. As part of the RDCRN, the Urea Cycle Disorders Consortium (UCDC) was created to study urea cycle disorders. The UCDC consists of a consortium of eight academic insitutions: Children's National Medical Center, Children's Hospital of Philadelphia, Vanderbilt University, Baylor College of Medicine, University of California Los Angeles, Yale University School of Medicine, Mount Sinai School of Medicine and Case Western Reserve University. All eight UCDC Centers are participating in the Longitudinal Study of Urea Cycle Disorders. HYPOTHESIS A longitudinal multidisciplinary investigation of the natural history, morbidity, and mortality in people with urea cycle disorders will improve treatment and outcome of this devastating group of disorders.
SPECIFIC AIMS The objective of this protocol is to conduct a longitudinal multidisciplinary investigation of the natural history, morbidity, and mortality in people with UCD. The research questions are: a. In the longitudinal cohort, what is the prevalance of specific morbid indicators of disease severity, including hyperammonemia, developmental disabilities, and various long-term renal and hepatic effects, as well as case-fatality associated with the various forms of UCD? b. What are the correlations between various biomarkers and disease severity and progression? c. What is the safety and efficacy of currently used and new UCD therapies?

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
General Clinical Research Centers Program (M01)
Project #
Application #
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Schools of Medicine
United States
Zip Code
Lanzieri, T M; Leung, J; Caviness, A C et al. (2017) Long-term outcomes of children with symptomatic congenital cytomegalovirus disease. J Perinatol 37:875-880
El-Hattab, Ayman W; Zarante, Ana Maria; Almannai, Mohammed et al. (2017) Therapies for mitochondrial diseases and current clinical trials. Mol Genet Metab 122:1-9
Jin, Haoxing Douglas; Demmler-Harrison, Gail J; Coats, David K et al. (2017) Long-term Visual and Ocular Sequelae in Patients With Congenital Cytomegalovirus Infection. Pediatr Infect Dis J 36:877-882
Zeller, Meg H; Washington, Gia A; Mitchell, James E et al. (2017) Alcohol use risk in adolescents 2 years after bariatric surgery. Surg Obes Relat Dis 13:85-94
Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P et al. (2017) Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys. J Pediatr 190:100-107.e2
Zimmerman, Emily; Lau, Chantal (2017) The Development of the Mother-Infant Mutualistic Screening Scale. J Pediatr Mother Care 2:
Thakur, Neeta; Barcelo, Nicolas E; Borrell, Luisa N et al. (2017) Perceived Discrimination Associated With Asthma and Related Outcomes in Minority Youth: The GALA II and SAGE II Studies. Chest 151:804-812
Jenkins, Todd M; Boyce, Tawny W; Ralph Buncher, C et al. (2017) Accuracy of Self-Reported Weight Among Adolescent and Young Adults Following Bariatric Surgery. Obes Surg 27:1529-1532
Lopez, Adriana S; Lanzieri, Tatiana M; Claussen, Angelika H et al. (2017) Intelligence and Academic Achievement With Asymptomatic Congenital Cytomegalovirus Infection. Pediatrics 140:
El-Hattab, Ayman W; Almannai, Mohammed; Scaglia, Fernando (2017) Arginine and citrulline for the treatment of MELAS syndrome. J Inborn Errors Metab Screen 5:

Showing the most recent 10 out of 453 publications