Abdelrahim Abdrabou Sadek

Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction

Pediatric-onset ataxias often present clinically as developmental delay and intellectual disability, with prominent cerebellar atrophy as a key neuroradiographic finding. Here we describe a new clinically distinguishable recessive syndrome in 12 families with cerebellar atrophy together with ataxia, coarsened facial features and intellectual disability, due to truncating mutations in the sorting nexin gene SNX14, encoding a ubiquitously expressed modular PX domain–containing sorting factor. We found SNX14 localized to lysosomes and associated with phosphatidylinositol (3,5)-bisphosphate, a key component of late endosomes/lysosomes. Patient-derived cells showed engorged lysosomes and a slower autophagosome clearance rate upon autophagy induction by starvation. Zebrafish morphants for snx14 showed dramatic loss of cerebellar parenchyma, accumulation of autophagosomes and activation of apoptosis. Our results characterize a unique ataxia syndrome due to biallelic SNX14 mutations leading to lysosome-autophagosome dysfunction.

The genetic landscape of autism spectrum disorders

Autism spectrum disorders (ASDs) are a group of heterogeneous neurodevelopmental disorders that show impaired communication and socialization, restricted interests, and stereotypical behavioral patterns. Recent advances in molecular medicine and high throughput screenings, such as array comparative genomic hybridization (CGH) and exome and whole genome sequencing, have revealed both novel insights and new questions about the nature of this spectrum of disorders. What has emerged is a better understanding about the genetic architecture of various genetic subtypes of ASD and correlations of genetic mutations with specific autism subtypes. Based on this new information, we outline a strategy for advancing diagnosis, prognosis, and counseling for patients and families.

Study of the C677T and 1298AC polymorphic genotypes of MTHFR Gene in autism spectrum disorder

Background Autism is currently known as “a behaviorally defined syndrome” manifested as impairment in social communication, repetitive routines and restricted interests. There is an increased risk of ASDs associated with common mutations affecting the folate/methylation cycle. Aim The aim of this study was to identify C677T and 1298AC polymorphic genotypes of MTHFR gene among a sample of Egyptian children with autism and to make a phenotype-genotype correlation for the autistic patients. Methods This case-control study was carried out from 2013 through 2015. The study included 31 children with autism and 39 children in a normal control group, the mean age of patients and control was comparable (4.5 years± 2) with males predominant in both groups. We used DSM-V-TR criteria, Stanford-Binet intelligence scale V and childhood autism rating scale (CARS) for assessments. Genotyping for MTHFR gene polymorphic loci C677T and 1298AC was performed on amplified DNA by PCR with subsequent reverse hybridization and restriction fragment length polymorphisms analysis. Data were analyzed by SPSS version 11, using Chi-Square, independent-samples t-test, and ANOVA. Results There was significant relationship between low birth weight and occurrence of autism (p<0.01), and between delayed motor and social milestones in cases of autism compared to controls (p<0.01). Heterozygosity for A1298C polymorphism was highest among patients (41.9%) followed by 35.5% mutant genotype CC and 22.6% normal AA (wild) type and Allele C was detected in patients more than in control (56.45% vs. 11.54%) (p<0.001). For C667T polymorphism, heterozygosity was also highest among patients (48.4%) followed by wild type genotypes C677 (38.7%) and 12.9% for mutant genotypes 667T. Allele T appeared more in patients than control (31.10 %vs. 5.13%) (p<0.00). Heterozygosity for CT and A–C genotypes were detected equally (46.2%) among patients with severe autism (according to CARS). Conclusion There is a significant association between severity and occurrence of autism with MTHFR gene polymorphisms C677T and A1298C. Further studies are needed on a larger scale to explore other genes polymorphisms that may be associated with autism, to correlate the genetic basis of autism.

Outcome of Guillain - Barré Syndrome in Children: A prospective cohort study in a tertiary hospital in Upper Egypt

Introduction Guillain-Barré syndrome is the most common cause of acute flaccid paralysis in children, and defined as an acute inflammatory polyneuropathy. The objective of this study was to assess the clinico-laboratory profile, and outcome of Guillain-Barré syndrome in children at Sohag University Hospital. Methods This prospective cohort observational study was conducted in 2014–2015. The included children were subjected to through medical history and detailed systemic and neurological examination. Nerve conduction studies and cerebrospinal fluid analysis were done for all patients. Follow up was done at three and six months both clinically and by nerve conduction studies. Results This study included 50 patients (27 males/23 females) with median age of 2.92 years. Upper respiratory tract infections were the most common antecedent infections (50%) and the neurological findings were weakness of both lower limbs and pain in all patients (100%) followed by sphincteric dysfunction (26%) while cranial neuropathies were found in 4%. Nerve conduction study revealed that acute inflammatory demyelinating polyradiculoneuropathy was found in 52% of cases, acute motor axonal neuropathy in 36% of cases, whereas acute motor-sensory axonal neuropathy was found in 6% of cases. The outcome was good in about 78% of cases, Hughes motor scale revealed that 58% were healthy, 18% had minor signs or symptoms, 12% walked without support, 6% walked with support, and 6% were bed ridden. Conclusion The outcome was favorable, although a minority of patients suffered neurological deficit. Immediate administration of intravenous immunoglobulin reduced mortality and disability.

Pattern and Outcome of Acute Disseminated Encephalomyelitis (ADEM) in Children: Experience in a Tertiary Center, Upper Egypt

Introduction Acute disseminated encephalomyelitis (ADEM) is an immune mediated disease of the brain. Although it occurs in all ages, most reported cases are in children and adolescents. The aims of this study were to study the clinical pattern and outcome of ADEM in children in a tertiary center in Upper Egypt and to determine the effect of combined use of steroids and IVIg on outcome. Methods This observational study was carried out from January 2014 through December 2014 in the Pediatric Department of Sohag University Hospital (Egypt). All children diagnosed as ADEM during a one year period were included in this study. The treatments used were IV methylprednisolone followed by oral prednisone taper and intravenous immunoglobulin for severe cases. All studied cases were followed up and reevaluated at three months and six months. We used SPSS version 10 and Chi Square, Spearman’s test and t-test for data analysis. Results Eighteen children were included in this study (10 males and 8 females), the average age was 5.5 ± 0.9 years. Prodroma was found in 72.22% of the cases while the main complaint was encephalopathy (83.33%) followed by seizures (11.11%). The neurological findings were convulsions in 83.33%, quadriparesis (33.33%), hemiparesis (33.33), bladder involvement (both retention and incontinence) in 61.11%, and cranial nerve affection (11.11%). Demyelination patches were multifocal in 50%, mainly subcortical in 27.78%. Intelligence quotient (IQ) assessment after 6 months follow up showed that 50% were below average, 25% had mild MR while neurological evaluation showed that 75% of our patients were completely cured. The predictors of better outcome were; children related to the age group (1–4 years) (p = 0.01), children with higher GCS (6–14) (p = 0.01), and children who received steroids on the first day of symptoms and intravenous immunoglobulin in the first week (p = 0.03). Conclusion The clinical pattern of acute disseminated encephalomyelitis is variable, and a disturbed level of consciousness was the most common presentation. The outcome is generally favorable although motor deficit and cognitive impairment were reported. The combined use of steroids and IVIg has substantial effect on the outcome in children with ADEM.

Metabolic profile of oxidative stress and trace elements in febrile seizures among children

Febrile seizures (FS) are frequent convulsive disorders, occurring in infants and young children. The present study aims to assess and compare the serum levels of oxidative stress markers and some essential trace minerals in FS with normal or abnormal EEG and evaluate the effect of antioxidant therapy on the clinical outcome. This study has been carried out on 80 children with FS (40 with simple FS and 40 with complex FS) and 40 febrile children without seizures. Clinical and EEG findings were recorded for the included patients. Biochemical assays of serum nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), copper (Cu), zinc (Zn) and selenium (Se), using colorimetric methods, were measured in the studied groups. The overall results showed an increased values of NO, MDA and Cu with decreased values of SOD, Zn and Se in patients with FS (simple and complex) in comparison with febrile children without seizures (p < 0.05 for all). Additionally, NO and MDA was increased in complex FS patients with EEG abnormalities in comparison with complex FS with normal EEG findings (p < 0.05); NO and MDA were also significantly decreased after valproate therapy in complex FS patients (p < 0.05 for all). In conclusions, oxidative stress, decreased Zn and Se with increased Cu may play a role in FS. Valproate improves the oxidative stress status in complex FS.

Pediatric self-inflicted eye trauma due to a major depressive disorder

Self-inflicted eye trauma is a serious form of self-harm as it may lead to irreversible visual disability. Diagnosing self-inflicted ocular injuries, in all its forms, can be quite challenging. In this report, we are presenting a 5-year-old girl presented to Sohag University Outpatient Clinic with a history of repeated attacks of bilateral eye redness with blood-tinged strands removed from her eyes. After ocular examination, inferior bulbar conjunctival injection with blood-tinged strands were found. After careful examination of the strands, it was discovered that they were actual threads of cloth due to self-inflicted eye injury. Following psychiatric consultation, the patient was diagnosed as having a major depressive disorder. The case was subject to pharmacological and psychotherapeutic treatment, and showed significant improvement within two months of starting treatment as regard to depressive symptoms and self-injury behaviors. Although self-inflicted ocular injuries due to pediatric mood disorders are rare, it should be suspected in any case of unexplained chronic conjunctivitis.

Diagnostic value of lumbar puncture among infants and children presenting with fever and convulsions

Introduction Central nervous system (CNS) infections can be categorized according to the nature of the infectious pathogen into viral, bacterial, protozoan, or fungal. The diagnosis of diffuse CNS infections depends on examination of cerebrospinal fluid (CSF) obtained by lumbar puncture (LP). The aim of this work was to determine the diagnostic value of CSF analysis in infants and children presenting with fever and convulsions. Methods Detailed clinical data of infants and children included in this study were collected with special reference to the course and duration of the illness, description of the convulsions, consciousness level, signs of increased intracranial pressure, and signs of meningeal irritation. Lumbar puncture and chemical and bacteriological analyses of the obtained cerebrospinal fluid were done for all of the children. Results The total number of children included in the study was 85, they had a median age 19 months, and 88% of them had generalized convulsions. CSF examination revealed that 20% had abnormal physical findings, while 23.5% had abnormal white blood cell count (WBC) (CSF Pleocytosis). CSF cultures were done in three cases with the highest White blood cells (WBCs), and streptococcus pneumoniae was present in all three cases. Conclusion This study found that CNS infections are not uncommon in infants and children presenting with fever and convulsions in our locality, and acute bacterial meningitis cannot be excluded. However, its presence in the absence of clinical symptoms and signs of meningeal irritation is a remote possibility, but it should always be considered.