Citation: Batshaw ML, Tuchman M, Summar M, Seminara J, Members of the Urea Cycle Disorders Consortium. A longitudinal study of urea cycle disorders. Mol Genet Metab. 2014;113(0):127-130. doi:10.1016/j.ymgme.2014.08.001.
Purpose: To summarize studies of 614 patientsa with urea cycle disorders (UCDs) enrolled in a longitudinal study performed by the Urea Cycle Disorders Consortium (UCDC) from 2006 to 2013.b
- The overall average birth prevalence of UCDs in the United States was estimated at 1/35,000, from which approximately 114 newborns with UCDs would be expected each year.
- 26% of patients presented with early onset (aged <30 days) hyperammonemia while 69% exhibited late onset (aged ≥31 days) of symptoms; 5% of patients remained “asymptomatic.”
- The mortality rate was 24% for patients with early-onset disease, and 11% for those with late-onset disease.
- Acute liver failure was the initial presenting symptom in at least 3 of 49 patients with symptomatic ornithine transcarbamylase (OTC) deficiency. The diagnosis of a UCD should be considered in patients with unexplained acute liver failure, dysfunction, or hepatocellular injury.
- On average patients experienced slightly less than 1 hyperammonemic event per year, with infection being the most common precipitant (33% of events).
- When longitudinally tested, mean plasma glutamine levels were predictive of neurocognitive outcome.
- Low-protein diets required to sustain patients with UCDs appeared to yield pediatric weight levels within the expected range, while height velocity was lower than expected.
- Plasma levels of the branched chain amino acids (BCAA) were significantly reduced in patients who were treated with phenylbutyrate, indicating that patients with UCDs should be frequently monitored for deficiencies in BCAA and given supplements if needed.
- Prior to the use of alternative pathway therapies in the early 1980s, UCDs were associated with an 86% 1-year mortality rate in patients with early-onset UCDs,1 while in the late 1990s, early-onset UCDs were associated with an approximately 50% 5-year mortality rate. The apparent improvements in mortality rate published herein could be attributed to neonatal screening, standardization of treatment, and/or earlier recognition of symptoms.
bThe results in this paper are the outcome of hypothesis-driven data mining projects from the longitudinal study, most of which are fully presented in other publications.