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Sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD; MIM #616084) is an autosomal recessive disorder of mitochondrial and cytosolic tRNA processing caused by pathogenic, biallelic variants in TRNT1. Other features of this disorder include central nervous system, renal, cardiac, ophthalmological features, and sensorineural hearing impairment. SIFD was first described in 2013 and to date, it has been reported in 46 patients. Herein, we review the literature and describe two siblings with SIFD and note the novel phenotype of hypoglycemia in the context of growth hormone (GH) deficiency. GH deficiency without hypoglycemia has previously been reported in three patients with SIFD, but GH deficiency had not been firmly ascribed to SIFD. We propose to expand the phenotype to include GH deficiency, hypoglycemia, and previously unreported dysmorphic features. Furthermore, we highlight the intrafamilial variability of the disease by the discordance of our patients' clinical phenotypes and biochemical profiles measured by untargeted metabolomics analysis. Several metabolomic abnormalities were observed in both patients, and these may represent a potential biochemical signature for SIFD.

Riboflavin transporter deficiency (RTD) (MIM #614707) is a neurogenetic disorder with its most common manifestations including sensorineural hearing loss, peripheral neuropathy, respiratory insufficiency, and bulbar palsy. Here, we present a 2-year-old boy whose initial presentation was severe macrocytic anemia necessitating multiple blood transfusions and intermittent neutropenia; he subsequently developed ataxia and dysarthria. Trio-exome sequencing detected compound heterozygous variants in SLC52A2 that were classified as pathogenic and a variant of uncertain significance. Bone marrow evaluation demonstrated megaloblastic changes. Notably, his anemia and neutropenia resolved after treatment with oral riboflavin, thus expanding the clinical phenotype of this disorder. We reiterate the importance of starting riboflavin supplementation in a young child who presents with macrocytic anemia and neurological features while awaiting biochemical and genetic work up. We detected multiple biochemical abnormalities with the help of untargeted metabolomics analysis associated with abnormal flavin adenine nucleotide function which normalized after treatment, emphasizing the reversible pathomechanisms involved in this disorder. The utility of untargeted metabolomics analysis to monitor the effects of riboflavin supplementation in RTD has not been previously reported.

Relapse of anti-NMDA receptor (NMDAR) encephalitis should be considered in all patients with history of anti-NMDAR encephalitis presenting with new acute-onset encephalopathy or psychosis.

Although the detrimental effects of math anxiety in adults are well understood, few studies have examined how it affects younger children who are beginning to learn math in a formal academic setting. Here, we examine the relationship between math anxiety and math achievement in second and third graders. In response to the need for a grade-appropriate measure of assessing math anxiety in this group we first describe the development of Scale for Early Mathematics Anxiety (SEMA), a new measure for assessing math anxiety in second and third graders that is based on the Math Anxiety Rating Scale. We demonstrate the construct validity and reliability of the SEMA and use it to characterize the effect of math anxiety on standardized measures of math abilities, as assessed using the Mathematical Reasoning and Numerical Operations subtests of the Wechsler Individual Achievement Test (WIAT-II). Math achievement, as measured by the WIAT-II Math Composite score, was significantly and negatively correlated with SEMA but not with trait anxiety scores. Additional analyses showed that SEMA scores were strongly correlated with Mathematical Reasoning scores, which involves more complex verbal problem solving. SEMA scores were weakly correlated with Numerical Operations which assesses basic computation skills, suggesting that math anxiety has a pronounced effect on more demanding calculations. We also found that math anxiety has an equally detrimental impact on math achievement regardless of whether children have an anxiety related to numbers or to the situational and social experience of doing math. Critically, these effects were unrelated to trait anxiety, providing the first evidence that the specific effects of math anxiety can be detected in the earliest stages of formal math learning in school. Our findings provide new insights into the developmental origins of math anxiety, and further underscore the need to remediate math anxiety and its deleterious effects on math achievement in young children.

Functional and structural maturation of networks comprised of discrete regions is an important aspect of brain development. The default-mode network (DMN) is a prominent network which includes the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), medial temporal lobes (MTL), and angular gyrus (AG). Despite increasing interest in DMN function, little is known about its maturation from childhood to adulthood. Here we examine developmental changes in DMN connectivity using a multimodal imaging approach by combining resting-state fMRI, voxel-based morphometry and diffusion tensor imaging-based tractography. We found that the DMN undergoes significant developmental changes in functional and structural connectivity, but these changes are not uniform across all DMN nodes. Convergent structural and functional connectivity analyses suggest that PCC-mPFC connectivity along the cingulum bundle is the most immature link in the DMN of children. Both PCC and mPFC also showed gray matter volume differences, as well as prominent macrostructural and microstructural differences in the dorsal cingulum bundle linking these regions. Notably, structural connectivity between PCC and left MTL was either weak or non-existent in children, even though functional connectivity did not differ from that of adults. These results imply that functional connectivity in children can reach adult-like levels despite weak structural connectivity. We propose that maturation of PCC-mPFC structural connectivity plays an important role in the development of self-related and social-cognitive functions that emerge during adolescence. More generally, our study demonstrates how quantitative multimodal analysis of anatomy and connectivity allows us to better characterize the heterogeneous development and maturation of brain networks.

The inferior parietal lobule (IPL) of the human brain is a heterogeneous region involved in visuospatial attention, memory, and mathematical cognition. Detailed description of connectivity profiles of subdivisions within the IPL is critical for accurate interpretation of functional neuroimaging studies involving this region. We separately examined functional and structural connectivity of the angular gyrus (AG) and the intraparietal sulcus (IPS) using probabilistic cytoarchitectonic maps. Regions-of-interest (ROIs) included anterior and posterior AG subregions (PGa, PGp) and 3 IPS subregions (hIP2, hIP1, and hIP3). Resting-state functional connectivity analyses showed that PGa was more strongly linked to basal ganglia, ventral premotor areas, and ventrolateral prefrontal cortex, while PGp was more strongly connected with ventromedial prefrontal cortex, posterior cingulate, and hippocampus-regions comprising the default mode network. The anterior-most IPS ROIs, hIP2 and hIP1, were linked with ventral premotor and middle frontal gyrus, while the posterior-most IPS ROI, hIP3, showed connectivity with extrastriate visual areas. In addition, hIP1 was connected with the insula. Tractography using diffusion tensor imaging revealed structural connectivity between most of these functionally connected regions. Our findings provide evidence for functional heterogeneity of cytoarchitectonically defined subdivisions within IPL and offer a novel framework for synthesis and interpretation of the task-related activations and deactivations involving the IPL during cognition.

Objective: To discuss occurrence of Balint syndrome in the pediatric population. Background Balint syndrome is a clinical symptom triad of simultagnosia, ocular apraxia and optic ataxia, without occurrence of visual agnosia and with sparing of visual acuity. This occurs secondary to damage of bilateral occipito-parietal regions. This has been described in adults, usually secondary to strokes or tumors. The syndrome is rarely reported in pediatric literature. Design/Methods: Described is a case report of three children seen at a tertiary pediatric hospital, diagnosed with Balint syndrome. Results: Case 1 was a 7 year old male with severe traumatic brain injury, following a motor vehicle accident. Imaging showed damage to the parietal regions, along with minor damage to the cerebellar, frontal and temporal lobes. He showed difficulties in multi-tasking and in maintaining attention, along with the Balint9s symptom triad. He had improvement by 6 months, though he had residual hemiparesis along with memory and attention problems. Case 2 was a 5 year old female with a strong family history of stroke, presenting with new onset seizures. Imaging suggested bilateral parieto-occipital damage, secondary to stroke. However, magnetic resonance spectroscopy suggested a demyelinating disorder. Further workup indicated a mitochondrial disorder. Within a year of presentation, she had significant improvement with resolution of her Balint syndrome. Case 3 was a two and a half year old female who developed herpes encephalitis, resulting in damage to bilateral hippocampi and occipitoparietal regions. Along with the symptom triad, she had marked anterograde amnesia and emotional lability. Her symptoms improved, with only mild deficits in daily living skills one year later. Conclusions: Balint syndrome occurs in children, though the symptom complex may not be easily recognized. Etiologies may vary. In children, resolution is common. Disclosure: Dr. Amin has nothing to disclose. Dr. Ehrreich has nothing to disclose. Dr. Kelly has nothing to disclose. Dr. Lebby has nothing to disclose. Dr. Hutchison has nothing to disclose.