TY - JOUR
T1 - Investigating neurological deficits in carriers and affected patients with ornithine transcarbamylase deficiency
AU - Sprouse, Courtney
AU - King, Jessica
AU - Helman, Guy
AU - Pacheco-Colón, Ileana
AU - Shattuck, Kyle
AU - Breeden, Andrew
AU - Seltzer, Rebecca
AU - Van Meter, John W.
AU - Gropman, Andrea L.
N1 - Funding Information:
This work was supported by 5U54HD061221. We also appreciate the support of the Intellectual and Development Disorders Research Center (IDDRC) grant: 5P30HD040677-13 . We thank all the participants for taking part in our study, all the referring doctors and the National Urea Cycle Disorder Foundation.
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - Background: Urea cycle disorders are caused by dysfunction in any of the six enzymes and two transport proteins involved in urea biosynthesis. Our study focuses on ornithine transcarbamylase deficiency (OTCD), an X-linked disorder that results in a dysfunctional mitochondrial enzyme, which prevents the synthesis of citrulline from carbamoyl phosphate and ornithine. This enzyme deficiency can lead to hyperammonemic episodes and severe cerebral edema. The objective of this study was to use a cognitive battery to expose the cognitive deficits in asymptomatic carriers of OTCD. Materials and methods:: In total, 81 participants were recruited as part of a larger urea cycle disorder imaging consortium study. There were 25 symptomatic participants (18 female, 7 male, 25.6. years ± 12.72 years), 20 asymptomatic participants (20 female, 0 male, 37.6. years ± 15.19 years), and 36 healthy control participants (21 female, 15 male, 29.8. years ± 13.39 years). All participants gave informed consent to participate and were then given neurocognitive batteries with standard scores and T scores recorded. Results:: When stratified by symptomatic participant, asymptomatic carrier, and control, the results showed significant differences in measures of executive function (e.g. CTMT and Stroop) and motor ability (Purdue Assembly) between all groups tested. Simple attention, academic measures, language and non-verbal motor abilities showed no significant differences between asymptomatic carriers and control participants, however, there were significant differences between symptomatic and control participant performance in these measures. Conclusions:: In our study, asymptomatic carriers of OTCD showed no significant differences in cognitive function compared to control participants until they were cognitively challenged with fine motor tasks, measures of executive function, and measures of cognitive flexibility. This suggests that cognitive dysfunction is best measurable in asymptomatic carriers after they are cognitively challenged.
AB - Background: Urea cycle disorders are caused by dysfunction in any of the six enzymes and two transport proteins involved in urea biosynthesis. Our study focuses on ornithine transcarbamylase deficiency (OTCD), an X-linked disorder that results in a dysfunctional mitochondrial enzyme, which prevents the synthesis of citrulline from carbamoyl phosphate and ornithine. This enzyme deficiency can lead to hyperammonemic episodes and severe cerebral edema. The objective of this study was to use a cognitive battery to expose the cognitive deficits in asymptomatic carriers of OTCD. Materials and methods:: In total, 81 participants were recruited as part of a larger urea cycle disorder imaging consortium study. There were 25 symptomatic participants (18 female, 7 male, 25.6. years ± 12.72 years), 20 asymptomatic participants (20 female, 0 male, 37.6. years ± 15.19 years), and 36 healthy control participants (21 female, 15 male, 29.8. years ± 13.39 years). All participants gave informed consent to participate and were then given neurocognitive batteries with standard scores and T scores recorded. Results:: When stratified by symptomatic participant, asymptomatic carrier, and control, the results showed significant differences in measures of executive function (e.g. CTMT and Stroop) and motor ability (Purdue Assembly) between all groups tested. Simple attention, academic measures, language and non-verbal motor abilities showed no significant differences between asymptomatic carriers and control participants, however, there were significant differences between symptomatic and control participant performance in these measures. Conclusions:: In our study, asymptomatic carriers of OTCD showed no significant differences in cognitive function compared to control participants until they were cognitively challenged with fine motor tasks, measures of executive function, and measures of cognitive flexibility. This suggests that cognitive dysfunction is best measurable in asymptomatic carriers after they are cognitively challenged.
KW - Asymptomatic carriers
KW - Cognitive function
KW - Metabolic disease
KW - Ornithine transcarbamylase deficiency
KW - Urea cycle disorders
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U2 - 10.1016/j.ymgme.2014.05.007
DO - 10.1016/j.ymgme.2014.05.007
M3 - Article
C2 - 24881970
AN - SCOPUS:84908506508
SN - 1096-7192
VL - 113
SP - 136
EP - 141
JO - Molecular genetics and metabolism
JF - Molecular genetics and metabolism
IS - 1
ER -