Intellectual, adaptive, and behavioral functioning in children with urea cycle disorders

Abstract

Inborn errors of urea synthesis lead to an accumulation of ammonia in blood and brain and result in high rates of mortality and neurodevelopmental disability. This study seeks to characterize the cognitive, adaptive, and emotional/behavioral functioning of children with urea cycle disorders (UCDs). These domains were measured through testing and parent questionnaires in 92 children with UCDs [33 neonatal onset (NO), 59 late onset (LO)]. Results indicate that children who present with NO have poorer outcome than those who present later in childhood. Approximately half of the children with NO performed in the range of intellectual disability (ID), including a substantial number ( approximately 30%) who were severely impaired. In comparison, only a quarter of the LO group was in the range of ID. There is also evidence that the UCD group has difficulties in aspects of emotional/behavioral and executive skills domains. In conclusion, children with UCDs present with a wide spectrum of cognitive outcomes. Children with NO disease have a much higher likelihood of having an ID, which becomes even more evident with increasing age. However, even children with LO UCDs demonstrate evidence of neurocognitive and behavioral impairment, particularly in aspects of attention and executive functioning.

Figure 1

Cognitive Range Across All Subjects Ages 3 – 16: Neonatal (NO) vs. Late Onset (LO) and by Diagnosis* *Includes estimated IQ scores for children unable to complete testing in their age range who were excluded from table 3 NO (n=16), LO (n=52), AL deficiency (n=10, 40% NO), AS deficiency (n=12, 58% NO), OTC (n=36, 8% NO) . Average to Above Average (□); Borderline/Low (); Mild Intellectual Disability (); Moderate/Severe Intellectual Disability (■).

Figure 2

UCD Performance on the BRIEF for ages 6–16 Relative to a Normative Population* *INH = Inhibit, SHF = Shift, EMC = Emotional Control, INI = Initiate, WKM = Working Memory, P/O = Plan/Organize, ORG = Organization of Materials, MON = Monitor, BRI = Behavioral Regulation Index, MI = Metacognition Index, GEC = Global Executive Composite. UCD Group (●); Normative mean (solid line); 1 standard deviation (dashed line)

Figure 3

UCD Subjects ages 3–16: Child Behavior Checklist. Clinically Significant T ≥70 (■); At Risk T = 60–79 (); Within Normal Limits (◻)