1. Duvall MG, Pikman Y, Kantor DB, Ariagno K, Summers L, Sectish TC, Mullen MP. {{Pulmonary Hypertension Associated With Scurvy and Vitamin Deficiencies in an Autistic Child}}. {Pediatrics};2013 (Nov 4)
Restricted dietary intake is common among children with behavioral issues. Here we report a case of a severely autistic child who presented initially with limp but who soon developed cough, tachypnea, hypoxia, and tachycardia. An echocardiogram revealed evidence of pulmonary hypertension (PH) with severely dilated right ventricle and elevated right-sided pressures. The etiology of his PH was unclear but further laboratory evaluation demonstrated severe nutritional deficiencies, in particular an undetectable ascorbic acid (vitamin C) level as well as deficient levels of thiamine (vitamin B1), pyridoxine (vitamin B6), cobalamin (vitamin B12), and vitamin D. Repletion of these vitamins was associated with resolution of his PH and his musculoskeletal complaints. We report this case and a review of the relevant literature as a clinical lesson to expand the differential diagnosis of limp in children who may be difficult to assess as well as to report on an unusual association between severe vitamin deficiencies and PH.
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2. Garg S, Green J, Leadbitter K, Emsley R, Lehtonen A, Evans DG, Huson SM. {{Neurofibromatosis Type 1 and Autism Spectrum Disorder}}. {Pediatrics};2013 (Nov 4)
OBJECTIVE:To determine the prevalence of autism spectrum disorder (ASD) in Neurofibromatosis Type 1 (NF1).METHODS:Second-phase population-based epidemiologic study using an allcase NF1 registry in a defined UK 4.1 million population area. A total of 109 (52.7%) of 207 responders from the initial screening phase were grouped by using the parent-rated Social Responsiveness Scale (SRS) as significant ASD (SRS>/=76; n = 32), moderate ASD (SRS >/= 60<76; n = 29), or non-ASD (SRS <60, n = 48). Twenty-three cases from the significant ASD group, 16 from moderate ASD, and 8 from non-ASD (total n = 47), invited proportionately by random selection, were seen for detailed confirmatory ascertainment. Assessments on Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Scale-Generic, and verbal IQ were combined by using standard Collaborative Program for Excellence in Autism criteria into an ASD categorization for each case (ASD, broad ASD with partial features, non-ASD). A preplanned weighted analysis was used to derive prevalence estimates for the whole population.RESULTS:Fourteen (29.5%) of 47 showed ASD, 13 (27.7%) broad ASD, and 20 (42.5%) non-ASD. The ASD/broad ASD group showed male predominance (1.7:1.0), but did not differ significantly from the non-ASD group on IQ, age, socioeconomic status, inheritance, physical severity, or education. The population prevalence estimate is 24.9% ASD (95% confidence interval 13.1%-42.1%) and 20.8% broad ASD (95% confidence interval 10.0%-38.1%); a total of 45.7% showing some ASD spectrum phenotype.CONCLUSIONS:Findings indicate high prevalence of ASD in NF1, with implications for clinical practice and further research into NF1 as a single-gene model for autism.
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3. Nuytens K, Tuand K, Di Michele M, Boonen K, Waelkens E, Freson K, Creemers JW. {{Platelets of mice heterozygous for neurobeachin, a candidate gene for autism spectrum disorder, display protein changes related to aberrant protein kinase A activity}}. {Mol Autism};2013 (Nov 4);4(1):43.
BACKGROUND: Neurobeachin (NBEA) has been identified as a candidate gene for autism spectrum disorders (ASD) in several unrelated patients with alterations in the NBEA gene. The exact function of NBEA, a multidomain scaffolding protein, is currently unknown. It contains an A-kinase anchoring protein (AKAP) domain which binds the regulatory subunit of protein kinase A (PKA) thereby confining its activity to specific subcellular regions. NBEA has been implicated in post-Golgi membrane trafficking and in regulated secretion. The mechanism of regulated secretion is largely conserved between neurons and platelets, and the morphology of platelet dense granules was found to be abnormal in several ASD patients, including one with NBEA haploinsufficiency. Platelet dense granules are secreted upon vascular injury when platelets are exposed to for instance collagen. Dense granules contain serotonin, ATP and ADP, which are necessary for platelet plug formation and vascular contraction. METHODS: To further investigate possible roles for NBEA in secretion or dense granule morphology, platelets from Nbea+/- mice were analyzed morphometrically, functionally and biochemically. A differential proteomics and peptidomics screen was performed between Nbea+/- and Nbea+/+ mice, in which altered Talin-1 cleavage was further investigated and validated in brain samples. Finally, the phosphorylation pattern of PKA substrates was analyzed. RESULTS: Platelet dense granules of Nbea+/- mice had a reduced surface area and abnormal dense-core halo, but normal serotonin-content. Nbea haploinsufficiency did not affect platelet aggregation and ATP secretion after collagen stimulation, although the platelet shape change was more pronounced. Furthermore, peptidomics revealed that Nbea+/- platelets contain significantly reduced levels of several actin-interacting peptides. Decreased levels were detected of the actin-binding head and rod domain of Talin-1, which are cleavage products of Calpain-2. This is most likely due to increased PKA-mediated phosphorylation of Calpain-2, which renders the enzyme less active. Analysis of other PKA substrates revealed both increased and reduced phosphorylation. CONCLUSION: Our results show the pleiotropic effects of alterations in PKA activity due to Nbea haploinsufficiency, highlighting the important function of the AKAP domain in Nbea in regulating and confining PKA activity. Furthermore, these results suggest a role for Nbea in remodeling the actin cytoskeleton of platelets.
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4. Reser JE. {{Solitary Mammals Provide an Animal Model for Autism Spectrum Disorders}}. {J Comp Psychol};2013 (Nov 4)
Species of solitary mammals are known to exhibit specialized, neurological adaptations that prepare them to focus working memory on food procurement and survival rather than on social interaction. Solitary and nonmonogamous mammals, which do not form strong social bonds, have been documented to exhibit behaviors and biomarkers that are similar to endophenotypes in autism. Both individuals on the autism spectrum and certain solitary mammals have been reported to be low on measures of affiliative need, bodily expressiveness, bonding and attachment, direct and shared gazing, emotional engagement, conspecific recognition, partner preference, separation distress, and social approach behavior. Solitary mammals also exhibit certain biomarkers that are characteristic of autism, including diminished oxytocin and vasopressin signaling, dysregulation of the endogenous opioid system, increased Hypothalamic-pituitary-adrenal axis (HPA) activity to social encounters, and reduced HPA activity to separation and isolation. The extent of these similarities suggests that solitary mammals may offer a useful model of autism spectrum disorders and an opportunity for investigating genetic and epigenetic etiological factors. If the brain in autism can be shown to exhibit distinct homologous or homoplastic similarities to the brains of solitary animals, it will reveal that they may be central to the phenotype and should be targeted for further investigation. Research of the neurological, cellular, and molecular basis of these specializations in other mammals may provide insight for behavioral analysis, communication intervention, and psychopharmacology for autism. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
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5. Wang L, Christophersen CT, Sorich MJ, Gerber JP, Angley MT, Conlon MA. {{Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder}}. {Mol Autism};2013 (Nov 4);4(1):42.
BACKGROUND: A recent report indicated that numbers of Sutterella spp. are elevated in gastrointestinal biopsies taken from children with autism spectrum disorder (ASD). We have recently reported changes in the numbers of some bacteria within the stool of ASD children, and now examine whether numbers of Sutterella spp. and some other mucosa-associated bacteria linked with gastrointestinal disease (Ruminococcus gnavus and Ruminococcus torques) are also altered in the stool of these children. FINDINGS: We show that numbers of Sutterella spp. are elevated in feces of ASD children relative to controls, and that numbers of R. torques are higher in the children with ASD with a reported functional gastrointestinal disorder than those without such a disorder. CONCLUSIONS: We show further evidence of changes in the gut microbiota of children with ASD and confirm that the abundance of Sutterella spp. is altered in stool.
