Fesih Aktar

CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration.

Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans.

Clinical features and prognosis with Guillain-Barré syndrome

Background: Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy commonly characterized by rapidly progressive, symmetric weakness and areflexia. Materials and Methods: We retrospectively assessed the clinical manifestations, results of electrodiagnostic tests, functional status and prognosis of 36 children diagnosed with GBS. Results: Based on clinical and electrophysiological findings, the patients were classified as having acute inflammatory demyelinating polyradiculoneuropathy (AIDP) (n = 25), acute motor axonal neuropathy (AMAN) (n = 10) and acute motor-sensory axonal neuropathy (AMSAN) (n = 1). Twenty (55.5%) patients were males and 16 (44.5%) patients were females. The mean age of the 36 patients was 68.1 ± 45.01 months (range, 6–180 months). Five (13.8%) patients were younger than 2 years. The most common initial symptoms were limb weakness, which was documented in 34 (94.4%) patients. In our study, 18 patients (51.4%) showed albuminocytological dissociation (raised protein concentration without pleocytosis) on cerebrospinal fluid (CSF) examination. Three patients (8.3%) required mechanical ventilation therapy during hospitalization. Unfortunately, three (8.3%) patients died; one patient had AIDP and two patients had axonal involvement (one case was AMAN and another case was AMSAN). When we compared the cases of residual sequel/dead and cases of complete recovery for neural involvement type including AIDP, AMAN and AMSAN, we did not find a statistically significant difference between the groups (P > 0.05). Conclusion: Our findings showed that cases of GBS was not uncommon in children younger than 2 years of age, and CSF protein level might be found high in the first week of the disease in about one half of the patients, with a higher rate of morbidity and mortality in patients with axonal involvement than in those with AIDP.

Brain Malformations Associated With Knobloch Syndrome—Review of Literature, Expanding Clinical Spectrum, and Identification of Novel Mutations

BACKGROUND Knobloch syndrome is a rare, autosomal recessive, developmental disorder characterized by stereotyped ocular abnormalities with or without occipital skull deformities (encephalocele, bone defects, and cutis aplasia). Although there is clear heterogeneity in clinical presentation, central nervous system malformations, aside from the characteristic encephalocele, have not typically been considered a component of the disease phenotype. METHODS Four patients originally presented for genetic evaluation of symptomatic structural brain malformations. Whole-genome genotyping, whole-exome sequencing, and confirmatory Sanger sequencing were performed. Using immunohistochemical analysis, we investigated the protein expression pattern of COL18A1 in the mid-fetal and adult human cerebral cortex and then analyzed the spatial and temporal changes in the expression pattern of COL18A1 during human cortical development using the Human Brain Transcriptome database. RESULTS We identified two novel homozygous deleterious frame-shift mutations in the COL18A1 gene. On further investigation of these patients and their families, we found that many exhibited certain characteristics of Knobloch syndrome, including pronounced ocular defects. Our data strongly support an important role for COL18A1 in brain development, and this report contributes to an enhanced characterization of the brain malformations that can result from deficiencies of collagen XVIII. CONCLUSIONS This case series highlights the diagnostic power and clinical utility of whole-exome sequencing technology-allowing clinicians and physician scientists to better understand the pathophysiology and presentations of rare diseases. We suggest that patients who are clinically diagnosed with Knobloch syndrome and/or found to have COL18A1 mutations via genetic screening should be investigated for potential structural brain abnormalities even in the absence of an encephalocele.

Determining the Independent Risk Factors and Mortality Rate of Nosocomial Infections in Pediatric Patients

The objective of this study was to determine the rate, independent risk factors, and outcomes of healthcare-associated infections in pediatric patients. This study was performed between 2011 and 2014 in pediatric clinic and intensive care unit. 86 patients and 86 control subjects were included in the study. Of 86 patients with nosocomial infections (NIs), there were 100 NIs episodes and 90 culture growths. The median age was 32.0 months. The median duration of hospital stay of the patients was 30.0 days. The most frequent pathogens were Coagulase-negative Staphylococcus, Acinetobacter spp., Klebsiella spp., and Candida spp. Unconsciousness, prolonged hospitalization, transfusion, mechanical ventilation, use of central venous catheter, enteral feeding via a nasogastric tube, urinary catheter, and receiving carbapenems and glycopeptides were found to be significantly higher in NIs patients. Multivariate logistic regression analysis showed prolonged hospitalization, neutropenia, and use of central venous catheter and carbapenems as the independent risk factors for NIs. In the univariate analysis, unconsciousness, mechanical ventilation, enteral feeding, use of enteral feeding via a nasogastric tube, H2 receptor blockers, and port and urinary catheter were significantly associated with mortality. In the multiple logistic regression analysis, only mechanical ventilation was found as an independent predictor of mortality in patients with NIs.

Congenital tuberculosis: presentation of a rare case.

Congenital tuberculosis is a rare disease with a high mortality rate. Congenital tuberculosis is considered the result of mother-to-child transmission from the placenta to the fetus, through the ingestion of the amniotic fluid, or via transplacental transmission through the umbilical vein. Given the non-specific clinical signs of tuberculosis, it is usually difficult to diagnose it. The case of a 48-day-old male infant hospitalized due to weight loss, fever, cough, hemoptysis, and respiratory distress for the past 20 days, is presented. In this period, he had received broad spectrum antibiotics but with no improvement. A chest x-ray showed the presence of consolidation and a cavitary lesion in the upper and middle left lung fields. Mycobacterium tuberculosis was detected by polymerase chain reaction in a bronchoalveolar lavage specimen. Congenital tuberculosis was diagnosed based on this finding; hence, a tuberculostatic regimen was started accordingly. The patient died 13 days after treatment initiation. Congenital tuberculosis should be considered in infants with weight loss, fever, cough, hemoptysis and respiratory distress.

A case of immune thrombocytopenic purpura presenting with intracranial hemorrhage

Abstract Immune thrombocytopenic purpura is an acute, generally considered a self-limiting benign disorder with a 60%-80% change of spontaneous recovery occurring usually within a few months after onset. Intracranial hemorrhage is a rare but life-threatening complication of childhood immune thrombocytopenic purpura. We report a 4-year-old girl who admitted with headache, vomiting, bleeding from noise and bruises on the extremities. Her neurological examination was normal. Based on laboratory finding she was diagnosed immune thrombocytopenic purpura and intracranial hemorrhage. We suggest that cranial imaging should be perform in patients with immune thrombocytopenic purpura admitted with bleeding symptoms, vomiting and headache even if they had no abnormal neurological signs.

Atypical presentation of herpes zoster in a case with acute myeloblastic leukemia

Abstract Herpes zoster (HZ) is often associated with painful erythematous vesicular eruptions of the skin or mucous membranes. Approximately 10% to 30% of the population will suffer from HZ during their lifetime. HZ is infrequent in healthy children. However, diminished cellular immunity seems to increase risk of reactivation because incidence increases with age and in immunocompromised states. We report a 7-year-old girl with acute myeloblastic leukemia HZ infection on the right palmar, elbow and forearm region (C7, C8 and T1 dermatomes). We want to indicate unusual localization of HZ on the acute myeloblastic leukemia child patient.

Comparison of Inflammatory Markers Between Adult and Pediatric Brucellosis Patients

Abstract Background Brucellosis is still endemic in many developing countries and frequently leads to misdiagnosis and treatment delays. Indirect inflammatory markers such as mean platelet volume (MPV), platelet distribution width (PDW), red cell distribution width (RDW), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have been identified as markers of inflammation. The present study aimed to evaluate and compare the levels of these markers for prognostic purposes, and to assess the correlation of C-reactive protein (CRP) with brucellosis in adults and children. Methods The study included 137 adults and 141 age- and gender-matched healthy controls, as well 71 children and 81 age- and gender-matched healthy controls. Hematological parameters and CRP were retrospectively recorded and compared between the adult and pediatric patients. Results The mean age of the adult patients (54% female) was 43.1 ± 15.4 years, whereas the mean age of the pediatric patients (50.7% male) was 9.5 ± 3.6 years. Significantly higher lymphocyte count, and lower neutrophil count, platelet count, RDW, MPV, NLR and PLR values were found in adult brucellosis patients compared with their healthy subjects, whereas higher lymphocyte count, PDW and lower neutrophil count, platelet count, MPV, NLR and PLR values were observed in pediatric brucellosis patients compared with the control subjects. Significantly higher neutrophil count (p=0.019) and NLR (p<0.001) were found in adult patients compared with the pediatric patients. Positive correlation was found between CRP and NLR (R2 = 0.052, P = 0.011), PLR (R2 = 0.061, P = 0.006) in adult patients. Conclusion Based on our findings, we consider that the use of complementary indirect markers such as MPV, NLR, PLR and RDW together with the CRP test – which is used concomitantly with serological diagnostic tests in situations where brucellosis is suspected – might be helpful in the diagnosis and follow-up of brucellosis, as well as in the evaluation of complications and response to therapy, in both adult and pediatric brucellosis patients. Disclosures All authors: No reported disclosures.

Protective effects of L-glutamine against toxicity of deltamethrin in the cerebral tissue

Background Deltamethrin (DLM) is a broad-spectrum synthetic dibromo-pyrethroid pesticide that is widely used for agricultural and veterinary purposes. However, human exposure to the pesticide leads to neurotoxicity. Glutamine is one of the principal, free intracellular amino acids and may also be an antioxidant. This study was undertaken in order to examine the neuroprotective and antioxidant potential of l-glutamine against DLM toxicity in female Wistar albino rats. Materials and methods The rats were divided into the following groups (n=10): Group I: control (distilled water; 10 mL/kg, po one dose), Group II: l-glutamine (1.5 g/kg, po one dose), Group III: DLM (35 mg/kg, po one dose), and Group IV: DLM (35 mg/kg, po one dose) and l-glutamine (1.5 g/kg, po one dose after 4 hours). Total oxidant status (TOS), total antioxidant status (TAS), tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels and apoptosis were evaluated in brain tissue. Results DLM-treated animals had a significant increase in brain biochemical parameters, as well as TOS and TAS. Furthermore, the histopathological examination showed neuronal cell degeneration in the cerebral tissue. l-Glutamine treatment decreased the elevated brain levels of TOS and neuronal cell degeneration. There was no difference in tumor necrosis factor-α, IL-1β, and IL-6 levels between the groups. Conclusion l-Glutamine may reduce the toxic effects of DLM in the cerebral tissue through antioxidant properties.

Evaluation of Risk Factors and Follow-Up Criteria for Severity of Snakebite in Children

Background Snakebites are an emergency medical condition and require rapid treatment procedures in children. Objectives This study aimed to present an overview of the demographic characteristics, clinical presentations, laboratory findings, severity, and complications that developed in pediatric patients due to snakebites. Patients and Methods A total of 151 children with snakebite were enrolled in the study. All patients had a history of snakebite obtained between June 2006 and August 2015 retrospectively. Results Duration of hospitalization (P < 0.001), rural occurrence (P < 0.001), white blood cell (WBC) count (P = 0.002), aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio (P = 0.010), hypoproteinemia (P = 0.001), hypoalbuminemia (P < 0.001), and hypocalcemia (P = 0.005) were significantly high in the severe snakebite group. WBC (P = 0.006) and AST/ALT ratio (P = 0.018) were significantly higher on the first day of the snakebite than on subsequent days. Conclusions Children admitted to the hospital due to snakebite should be monitored for at least 24 - 48 hours even if no signs of clinical envenomation could be observed. According to the severity of the disease, antivenom should be administered to the patients. Duration of hospitalization, rural occurrence, WBC count, AST/ALT ratio, CK, hypoproteinemia, hypoalbuminemia, and hypocalcemia can be associated with the severity of snakebite. WBC AST/ALT ratio can be used as follow-up criteria in children with snakebite