Abstract
Background and PurposeOrnithine transcarbamylase deficiency (OTCD) is an X-chromosome linked urea cycle disorder (UCD) that causes hyperammonemic episodes leading to white matter injury and impairments in executive functioning, working memory, and motor planning. This study aims to investigate differences in functional connectivity of two resting-state networks—default mode and set-maintenance—between OTCD patients and healthy controls.MethodsSixteen patients with partial OTCD and twenty-two control participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA) and region-of-interest (ROI) analyses, we identified the nodes that comprised each network in each group, and assessed internodal connectivity.ResultsGroup comparisons revealed reduced functional connectivity in the default mode network (DMN) of OTCD patients, particularly between the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) node and bilateral inferior parietal lobule (IPL), as well as between the ACC/mPFC node and the posterior cingulate cortex (PCC) node. Patients also showed reduced connectivity in the set-maintenance network, especially between right anterior insula/frontal operculum (aI/fO) node and bilateral superior frontal gyrus (SFG), as well as between the right aI/fO and ACC and between the ACC and right SFG.ConclusionInternodal functional connectivity in the DMN and set-maintenance network is reduced in patients with partial OTCD compared to controls, most likely due to hyperammonemia-related white matter damage. Because several of the affected areas are involved in executive functioning, it is postulated that this reduced connectivity is an underlying cause of the deficits OTCD patients display in this cognitive domain.
Highlights
Urea cycle disorders (UCD) are one of the most common groups of inborn errors of metabolism, with an estimated incidence of 1 in 30,000 births per year [1,2]
Internodal functional connectivity in the default mode network (DMN) and set-maintenance network is reduced in patients with partial Ornithine transcarbamylase deficiency (OTCD) compared to controls, most likely due to hyperammonemia-related white matter damage
Because several of the affected areas are involved in executive functioning, it is postulated that this reduced connectivity is an underlying cause of the deficits OTCD patients display in this cognitive domain
Summary
Urea cycle disorders (UCD) are one of the most common groups of inborn errors of metabolism, with an estimated incidence of 1 in 30,000 births per year [1,2]. Ornithine transcarbamylase deficiency (OTCD) is an X-linked recessive disorder and the most common UCD, with an incidence of 1 in 14,000 [5]. About 85% of the females are considered asymptomatic, while the remainder experience more severe symptoms such as behavioral and learning disabilities, protein intolerance, stroke-like episodes, and hyperammonemic coma [12,13]. Patients with OTCD often have trouble regulating their protein intake, which can result in episodes of hyperammonemia that cause substantial injury to the brain’s white matter [14]. Ornithine transcarbamylase deficiency (OTCD) is an X-chromosome linked urea cycle disorder (UCD) that causes hyperammonemic episodes leading to white matter injury and impairments in executive functioning, working memory, and motor planning. This study aims to investigate differences in functional connectivity of two resting-state networks—default mode and set-maintenance—between OTCD patients and healthy controls.
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