A longitudinal study of urea cycle disorders

Members Of The Urea Cycle Disorders Consortium

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)127-130
Number of pages4
JournalMolecular Genetics and Metabolism
Volume113
Issue number1
DOIs
StatePublished - Sep 1 2014
Externally publishedYes

Fingerprint

Inborn Urea Cycle Disorder
Longitudinal Studies
Urea
Ornithine Carbamoyltransferase Deficiency Disease
Ornithine Carbamoyltransferase
Phenylbutyrates
Branched Chain Amino Acids
Protein-Restricted Diet
Inborn Genetic Diseases
Data Mining
Biomarkers
Nutrition
Rare Diseases
Natural History
Glutamine
Ammonia
Canada
Data mining
Blood
Newborn Infant

Keywords

  • Ammonia
  • Argininosuccinate lyase
  • Hyperammonemia
  • Longitudinal study
  • Ornithine transcarbamylase
  • Urea cycle

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

A longitudinal study of urea cycle disorders. / Members Of The Urea Cycle Disorders Consortium.

In: Molecular Genetics and Metabolism, Vol. 113, No. 1, 01.09.2014, p. 127-130.

Research output: Contribution to journalArticle

Members Of The Urea Cycle Disorders Consortium 2014, 'A longitudinal study of urea cycle disorders', Molecular Genetics and Metabolism, vol. 113, no. 1, pp. 127-130. https://doi.org/10.1016/j.ymgme.2014.08.001
Members Of The Urea Cycle Disorders Consortium. / A longitudinal study of urea cycle disorders. In: Molecular Genetics and Metabolism. 2014 ; Vol. 113, No. 1. pp. 127-130.
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