Cross-sectional multicenter study of patients with urea cycle disorders in the United States

Abstract

Inherited urea cycle disorders comprise eight disorders (UCD), each caused by a deficiency of one of the proteins that is essential for ureagenesis. We report on a cross-sectional investigation to determine clinical and laboratory characteristics of patients with UCD in the United States. The data used for the analysis was collected at the time of enrollment of individuals with inherited UCD into a longitudinal observation study. The study has been conducted by the Urea Cycle Disorders Consortium within the Rare Diseases Clinical Research Network (RDCRN) funded by the National Institutes of Health. One-hundred eighty-three patients were enrolled into the study. Ornithine transcarbamylase (OTC) deficiency was the most frequent disorder (55%), followed by argininosuccinic aciduria (16%) and citrullinemia (14%). Seventy-nine percent of the participants were white (16% Latinos), and 6% were African American. Intellectual and developmental disabilities were reported in 39% with learning disabilities (35%) and half had abnormal neurological examination. Sixty-three percent were on a protein restricted diet, 37% were on Na-phenylbutyrate and 5% were on Na-benzoate. Forty-five percent of OTC deficient patients were on L-citrulline, while most patients with citrullinemia (58%) and argininosuccinic aciduria (79%) were on L-arginine. Plasma levels of branched-chain amino acids were reduced in patients treated with ammonia scavenger drugs. Plasma glutamine levels were higher in proximal UCD and in neonatal type disease. The RDCRN allows comprehensive analyses of rare inherited UCD, their frequencies and current medical practices.

Figure 1

The Urea Cycle Disorders Consortium currently consists of 8 sites. Children's National Medical Center (CNMC) The George Washington University, Washington, DC; Children's Hospital of Philadelphia (CHOP) University of Pennsylvania, Philadelphia, PA; Mount Sinai School of Medicine (MSSM), New York, NY; Yale University School of Medicine (YSM), New Haven CT; Vanderbilt University School of Medicine (VUSM), Nashville, TN; Baylor College of Medicine (BCM), Houston, TX; Case Western Reserve University (CWRU), Cleveland OH; University of California Los Angeles, Los Angeles, CA. Additional sites are being added at the time of this report in: Children's Hospital Boston (BCH); Harvard University, Boston, MA; The Children's Hospital (TCH), University of Colorado, Denver, CO; Oregon Health and Sciences University (OHSU), Portland, OR; University of Washington (UW), Seattle WA; Hospital for Sick Children (HSC), Toronto, Canada; University of Zürich (UZH), Zürich Switzerland. The Data Technology and Coordinating Center (DTCC) is located at the University of South Florida, Tampa, FL, and the National Urea Cycle Disorders Foundation (NUCDF) has its headquarters in La Canada, CA.

Figure 2

Frequency of the various urea cycle disorders among patients that have enrolled, registered but not enrolled, and the combination of the two groups. The category designated "Other" includes those patients with a highly likely diagnosis of a urea cycle disorder but for whom the specific diagnosis is still pending.