Infectious precipitants of acute hyperammonemia are associated with indicators of increased morbidity in patients with urea cycle disorders

Abstract

Objective: To prospectively characterize acute hyperammonemic episodes in patients with urea cycle disorders (UCDs) in terms of precipitating factors, treatments, and use of medical resources.

Study design: This was a prospective, longitudinal observational study of hyperammonemic episodes in patients with UCD enrolled in the National Institutes of Health-sponsored Urea Cycle Disorders Consortium Longitudinal Study. An acute hyperammonemic event was defined as plasma ammonia level >100 μmol/L. Physician-reported data regarding the precipitating event and laboratory and clinical variables were recorded in a central database.

Results: In our study population, 128 patients with UCD experienced a total of 413 hyperammonemia events. Most patients experienced between 1 and 3 (65%) or between 4 and 6 (23%) hyperammonemia events since study inception, averaging fewer than 1 event/year. The most common identifiable precipitant was infection (33%), 24% of which were upper/lower respiratory tract infections. Indicators of increased morbidity were seen with infection, including increased hospitalization rates (P = .02), longer hospital stays (+2.0 days; P = .003), and increased use of intravenous ammonia scavengers (+45%-52%; P = .003-.03).

Conclusion: Infection is the most common precipitant of acute hyperammonemia in patients with UCD and is associated with indicators of increased morbidity (ie, hospitalization rate, length of stay, and use of intravenous ammonia scavengers). These findings suggest that the catabolic and immune effects of infection may be a target for clinical intervention in inborn errors of metabolism.

Keywords: IV; Intravenous; LOS; Length of stay; OTC; Ornithine transcarbamylase; RDCRN; Rare Diseases Clinical Research Network; UCD; UCDC; Urea Cycle Disorders Consortium; Urea cycle disorder.

Conflict of interest statement

The authors declare no conflicts of interest.

Published by Mosby, Inc.

Figures

Figure 1

Infection is associated with markers of morbidity. A) Change in baseline plasma ammonias during acute hyperammonemia in patients with UCD. B) Length of stay for hospitalization due to various acute hyperammonemia precipitants in patients with UCD. C) Use of intravenous (IV) ammonia scavengers for the treatment of acute hyperammonemia due to various precipitants in patients with UCD. Other – indicates precipitants not due to dietary or infectious causes. Hatched bars indicate P < 0.05.