Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder

Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function

Childhood Traumas, Attachment And Alexithymia In Adolescents With Psychogenic Nonepileptic Seizure Type Of Conversion Disorder

Objective: In this cross-sectional study, childhood traumas, attachment security and alexithymia in adolescents with psychogenic nonepileptic seizures (PNES) were compared with those of adolescents without any psychiatric disorder using both semi-structured clinical interviews and self-report scales. Method: This study included 42 adolescents with PNES aged between 12-18 and 38 healthy adolescents who were matched with the study group in respect to socio-demographic variables. All adolescents and their parents were interviewed using Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version in order to evaluate psychiatric disorders. Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale for Children and Adolescents was used to examine the presence of PTSD symptoms. All adolescents completed the Childhood Trauma Questionnaire-28, Short Form of Inventory of Parent and Peer Attachment, Toronto Alexithymia Scale and Rosenberg Self Esteem Scale. Results: Adolescents with PNES had more emotional and sexual traumatic experiences and PTSD symptoms compared to the control group. PNES group perceived higher “communication” but lower “trust” in attachment relationships with their mothers and fathers. Higher alexithymia and lower self-esteem were determined in the PNES group. Childhood traumas, lifetime PTSD symptoms and alexithymia were found to be significant risk factors for PNES in adolescents. Conclusion: Results indicate that comorbid psychiatric disorders, traumatic experiences, attachment problems and alexithymia need to be evaluated and treated in adolescents with PNES.WoSScopu

Structural Abnormalities Of The Brain Other Than Molar Tooth Sign In Joubert Syndrome-Related Disorders

PURPOSE We performed a retrospective study in which we investigated malformations other than brainstem and vermian dysgenesis in Joubert syndrome-related disorders (JSRD). We investigated the frequency and type of structural abnormalities that coexist with the molar tooth sign (MTS) in JSRD. MATERIALS AND METHODS We searched our archive for the years 2002-2008 in order to find patients with the diagnosis of JSRD. Cranial magnetic resonance imaging studies of 20 patients with the diagnosis of JSRD were reviewed by two neuroradiologists. RESULTS In addition to known anomalies including callosal dysgenesis, heterotopia, polymicrogyria, atretic encephalocele, hypomy-elination, and nonobstructive dilatation of lateral ventricles; malformations that have not been previously reported were determined, including cerebellar folial disorganization, hippocampal malformation, temporal lob hypoplasia, ambient cistern lipoma, and parenchymal cyst. CONCLUSION Structural abnormalities associated with the MTS are not rare, and the additional imaging findings may help explain the neurological presentation in these patients.WoSScopu

Carnitine Palmitoyl Transferase II Deficiency in an Adolescent Presenting With Rhabdomyolysis and Acute Renal Failure

The most common cause of recurrent rhabdomyolysis in childhood is inherited metabolic disorders. Carnitine palmitoyl transferase II (CPT II) deficiency is a lipidosis and is a common cause of inherited recurrent myoglobinuria. The disease is inherited in autosomal recessive trait, and the clinical phenotype ranges from a severe and multisystemic infantile form to a milder muscle form, which is characterized with rhabdomyolysis and myoglobinuria. Exercise, infection, fasting, and cold are the most important triggering factors of rhabdomyolysis in CPT II deficiency. The severity of attacks is highly variable and some of these attacks may be complicated by acute renal failure. We report a case of a 13-year-old girl with recurrent rhabdomyolysis due to CPT II deficiency whose last attack was complicated by acute renal failure