TY - JOUR
T1 - A longitudinal study of urea cycle disorders
AU - Members Of The Urea Cycle Disorders Consortium
AU - Batshaw, Mark L.
AU - Tuchman, Mendel
AU - Summar, Marshall
AU - Seminara, Jennifer
AU - Summar, Marshall L.
AU - Baumgartner, Matthias R.
AU - Berry, Susan A.
AU - Cederbaum, Stephen
AU - Diaz, George A.
AU - Gallagher, Renata C.
AU - Harding, Cary O.
AU - Hoffmann, George
AU - Kerr, Douglas S.
AU - Lichter-Konecki, Uta
AU - McCandless, Shawn E.
AU - Merritt, J. Lawrence
AU - Schulze, Andreas
AU - Seashore, Margretta R.
AU - Stricker, Tamar
AU - Susan, Waisbren
AU - Derek, Wong
AU - Lee, Brendan
AU - Campeau, Philippe
AU - McGuire, Peter J.
AU - LeMons, Cynthia
AU - Oster-Granite, Mary Lou
AU - McCarter, Robert
AU - Yudkoff, Mark
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - The Urea Cycle Disorders Consortium (UCDC) is a member of the NIH funded Rare Diseases Clinical Research Network and is performing a longitudinal study of 8 urea cycle disorders (UCDs) with initial enrollment beginning in 2006. The consortium consists of 14 sites in the U.S., Canada and Europe. This report summarizes data mining studies of 614 patients with UCDs enrolled in the UCDC's longitudinal study protocol. The most common disorder is ornithine transcarbamylase deficiency, accounting for more than half of the participants. We calculated the overall prevalence of urea cycle disorders to be 1/35,000, with 2/3rds presenting initial symptoms after the newborn period. We found the mortality rate to be 24% in neonatal onset cases and 11% in late onset cases. The most common precipitant of clinical hyperammonemic episodes in the post-neonatal period was intercurrent infections. Elevations in both blood ammonia and glutamine appeared to be biomarkers for neurocognitive outcome. In terms of chronic treatment, low protein diet appeared to result in normal weight but decreased linear growth while N-scavenger therapy with phenylbutyrate resulted in low levels of branched chain amino acids. Finally, we found an unexpectedly high risk for hepatic dysfunction in patients with ornithine transcarbamylase deficiency. This natural history study illustrates how a collaborative study of a rare genetic disorder can result in an improved understanding of morbidity and disease outcome.
AB - The Urea Cycle Disorders Consortium (UCDC) is a member of the NIH funded Rare Diseases Clinical Research Network and is performing a longitudinal study of 8 urea cycle disorders (UCDs) with initial enrollment beginning in 2006. The consortium consists of 14 sites in the U.S., Canada and Europe. This report summarizes data mining studies of 614 patients with UCDs enrolled in the UCDC's longitudinal study protocol. The most common disorder is ornithine transcarbamylase deficiency, accounting for more than half of the participants. We calculated the overall prevalence of urea cycle disorders to be 1/35,000, with 2/3rds presenting initial symptoms after the newborn period. We found the mortality rate to be 24% in neonatal onset cases and 11% in late onset cases. The most common precipitant of clinical hyperammonemic episodes in the post-neonatal period was intercurrent infections. Elevations in both blood ammonia and glutamine appeared to be biomarkers for neurocognitive outcome. In terms of chronic treatment, low protein diet appeared to result in normal weight but decreased linear growth while N-scavenger therapy with phenylbutyrate resulted in low levels of branched chain amino acids. Finally, we found an unexpectedly high risk for hepatic dysfunction in patients with ornithine transcarbamylase deficiency. This natural history study illustrates how a collaborative study of a rare genetic disorder can result in an improved understanding of morbidity and disease outcome.
KW - Ammonia
KW - Argininosuccinate lyase
KW - Hyperammonemia
KW - Longitudinal study
KW - Ornithine transcarbamylase
KW - Urea cycle
UR - http://www.scopus.com/inward/record.url?scp=84908510356&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908510356&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2014.08.001
DO - 10.1016/j.ymgme.2014.08.001
M3 - Article
C2 - 25135652
AN - SCOPUS:84908510356
SN - 1096-7192
VL - 113
SP - 127
EP - 130
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1
ER -