A longitudinal study of urea cycle disorders

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 (UCD) 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 UCD 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 phenybutyrate 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.

Living with Intoxication-Type Inborn Errors of Metabolism: A Qualitative Analysis of Interviews with Paediatric Patients and Their Parents

“…Considerable progress in recent decades in the diagnosis and treatment of IT-IEM has resulted in a growing number of long-term survivors (de Baulny et al 2005;Batshaw et al 2014). The long-term medical care and support of patients and families requires insight into subjective psychosocial conditions and health-related quality of life (HrQoL) (Bullinger 2002).…”

Nutrition Management of Urea Cycle Disorders

“…Once a neonate who presented with hyperammonemia is stabilized, he or she will usually experience a period of metabolic stability or "honeymoon period" [ 14 ]. During this time, the infant is growing rapidly and has a relatively higher protein tolerance.…”

“…Intercurrent illness is the most common cause of hyperammonemia outside of the newborn period, and prompt treatment can prevent catabolism and be lifesaving [ 14 ]. Patients should have a MedicAlert ® bracelet (MedicAlert, Turlock, CA).…”

“…Glutamine is often a harbinger of high ammonia because it is a reservoir for ammonia (glutamine is synthesized from glutamate and ammonia). Both ammonia and glutamine are markers for neurocognitive outcomes [ 14 ]. Branched-chain amino acids, if low (either as a consequence of dietary restriction or Buphenyl ® therapy) [ 35 ], indicate the need for more protein.…”

“…Traditionally, however, outcomes have been suboptimal and characterized by early mortality, growth failure, chronic liver disease, and poor development [ 15 ]. Outcomes are better for those with late onset (11 % mortality) compared to neonatal onset (24 % mortality) [ 14 ]. Because of shortcomings of traditional therapies, liver transplantation is becoming a more viable and attractive option for many patients with UCD [ 16 ].…”