Genetic and clinical variations of developmental epileptic encephalopathies

Objective: The concept of 'developmental and epileptic encephalopathy (DEE)' recognises that in infants presenting with severe early-onset epilepsy, neurodevelopmental comorbidity may be attributable to both the underlying cause and to adverse effects of uncontrolled epileptic activity. There is no direct genotype - phenotype correlation in DEEs. This study aimed to report the genetic and phenotypic differences in patients with DEE. Methods: Genetic evaluations of the patients were performed due to epilepsy combined with developmental delay, epileptic encephalopathy, motor deficits, autistic features, or cognitive impairment. Patients were assessed for demographic characteristics, medical history, family history, psychomotor development, seizure control interventions, electroencephalogram (EEG) and magnetic resonance imaging (MRI) findings. Results: This study included 20 children aged 0-16 years who were diagnosed as having DEE.The types of DEE detected in our study were DEE 2, 4, 6B, 7, 11, 26, 30, 33, 35, 42, 58, 62, and 67.Status epilepticus was recorded in only DEE7. The most common EEG abnormality was multifocal epileptic discharges (35%,) followed by burst-suppression patterns in patients with neonatal-onset seizures. Thirteen of the children were aged over 2 years, two (15%) were non-ambulatory and six (46%) were non-verbal. MRI scans were normal in 80% of the patients. Refractory epilepsy seen in 33% of cases.De-novo mutation, microcephaly and dysmorphic findings accompany resistant seizures and are associated with poor prognosis Discussion: For patients with movement disorders, developmental delay, autism, and ID with or without epilepsy in any period of their life, next-generation sequencing is the only diagnostic technique available, with genetic analysis often being the only diagnostic method

The effect of the COVID-19 pandemic on pediatric emergency admissions and tendency towards prescribing antibiotics

Aim: To determine the changes in the diagnoses of patients admitted to pediatric emergency department due to infection and the change in the tendency towards prescribing antibiotics during the COVID-19 pandemic. Methods: Age, gender and the diagnoses of and the antibiotics prescribed for patients under the age of 18 who admitted to the pediatric emergency department on two separate days before and during the pandemic period were compared retrospectively. Results: It was found that the admissions to the pediatric emergency department decreased by 83% during the pandemic period compared to the pre-pandemic period. Upper respiratory tract infection (URTI) was diagnosed in 61.6% of the patients during the pre-pandemic period compared to 32.6% of the patients during the pandemic periods, indicating a statistically significant difference between the groups (p<0.001). The percentage of patients diagnosed with paranasal infection in the pandemic period was also significantly lower than in the pre-pandemic period. On the other hand, the percentages of patients diagnosed with urinary infection and diagnoses other than infection in the pandemic period were significantly higher than in the pre-pandemic period. Additionally, the percentage of patients who were prescribed amoxicillin-clavulanic acid (CAM) was significantly higher, whereas the percentage of patients who were prescribed Clarithromycin was significantly lower in the pandemic period than in the pre-pandemic period. Furthermore, it was determined that Oseltamivir was not prescribed during the pandemic period. Conclusions: Quarantines imposed due to the COVID-19 pandemic and the use of masks have reduced the incidence of upper and lower respiratory tract infections. In parallel, it was determined that the percentage of patients presented to the pediatric emergency department with the diagnosis of non-infectious diagnoses has increased. This result has been attributed to the use of masks and the attention paid to the hygiene, which caused a decrease in the incidence of infectious diseases, influenza in particular

Clinical and Laboratory Characteristics of Hyperprolactinemia in Children and Adolescents: National Survey

Conclusion: We present the largest cohort of children and adolescents with hyperprolactinemia in the literature to date. Hyperprolactinemia is more common in females and cabergoline is highly effective and practical to use in adolescents, due to its biweekly dosing. Indications for surgery in pediatric cases need to be revised

Lathosterolosis: a rare cholesterol metabolism disorder with a wide range of clinical variability

Objectives: Lathosterolosis is a rare autosomal recessive congenital disease that occurs due to homozygous or compound heterozygous mutations in the sterol C5-desaturase (SC5D) gene. We report a male patient with biallelic missense variant detected in the SC5D gene.Case presentation: An eight-month-old male patient was referred to the department of paediatric neurology for status epilepticus. He had no remarkable dysmorphic features except micrognathia, ptotic ear and thin-stranded hair. Laboratory tests revealed an alanine aminotransferase level of 502 IU/L and an aspartate aminotransferase level of 279 IU/L; other biochemical test results were normal. The brain MRI revealed atrophic changes in both hemispheres. A decrease in the volume of brain stem and thin corpus callosum were noticeable. Whole exome sequencing was performed because of consanguineous marriage and sibling death in his medical history, and the encountered features were consistent with suspected neurometabolic disease in the cranial imaging and the presence of borderline psychomotor retardation. A biallelic missense variant, c.656T > C p.(Leu219Ser), was identified in the SC5D gene.Conclusions: Lathosterolosis is a rare cholesterol metabolism disorder and can be presented with a wide range of clinical features by newly reported cases. Lathosterolosis should be considered in cases with cataracts, delayed neuromotor developmental milestones and high levels of live

Autoimmune complications and clinical outcomes of herpes simplex encephalitis in children: A case series

Objective: To report the neurologic prognosis and autoimmune complications of 16 cases of childhood herpes simplex virus encephalitis.Methods: The study was conducted at Sanliurfa Training and Research Hospital, Turkey from June 2017 to August 2019. The study included 16 pediatric patients aged between 6 months and 17 years (median age 77.7 months) who were diagnosed with herpes simplex virus type 1 encephalitis by pediatric infectious disease and pediatric neurology clinics. Patients were followed using patient records, and interviews at the pediatric neurology clinic or via the telephone. Clinical and demographic data, received therapies, neurologic prognosis and complications were evaluated.Results: Patients with and without autoimmune encephalitis were compared in terms of age, sex, symptom duration before treatment, initial cerebrospinal fluid protein, glucose, red blood count and white blood count but no significant difference was found. Autoimmune complications were seen in four patients. N-methyl-D-aspartate encephalitis was observed in three patients and choreoathetosis was seen in one patient. The average follow-up period was 48.3 months. Twenty-five percent of the patients were receiving multiple antiepileptic drug (AED) treatment, 43.8% were receiving single AED treatment and 31.3% were not receiving AED treatment at the end of the follow-up. Motor disability was observed in 12.5% and drug-resistant epilepsy was observed in 6.3% who had autoimmune complications.Conclusions: Seizures and movement disorders were controlled with immunotherapy and autoantibodies should be studied routinely. Treatment should be started early upon recognition of autoimmune complications through follow-up by measuring autoantibody levels and clinical examination results. Effective prevention and curative treatment modalities are needed to avoid herpes simplex virus encephalitis complications

Genotype and Phenotype Heterogeneity in Neonatal Diabetes: A Single Centre Experience in Turkey

OBJECTIVE: Neonatal diabetes mellitus (NDM) may be transient or permanent, and the majority is caused by genetic mutations. Early diagnosis is essential to select the patients who will respond to oral treatment. In this investigation, we aimed to present the phenotype and genotype of our patients with NDM and share our experience in a single tertiary center METHODS: A total of 16 NDM patients from 12 unrelated families are included in the study. The clinical presentation, age at diagnosis, perinatal and family history, consanguinity, gender, hemoglobin A1c, C-peptide, insulin, insulin autoantibodies, genetic mutations, and response to treatment are retrospectively evaluated. RESULTS: The median age at diagnosis of diabetes was five months (4 days-18 months) although six patients with a confirmed genetic diagnosis were diagnosed >6 months. Three patients had KCNJ11 mutations, six had ABCC8 mutations, three had EIF2AK3 mutations, and one had a de novo INS mutation. All the permanent NDM patients with KCNJ11 and ABCC8 mutations were started on sulfonylurea treatment resulting in a significant increase in C-peptide level, better glycemic control, and discontinuation of insulin. CONCLUSION: Although NDM is defined as diabetes diagnosed during the first six months of life, and a diagnosis of type 1 diabetes is more common between the ages of 6 and 24 months, in rare cases NDM may present as late as 12 or even 24 months of age. Molecular diagnosis in NDM is important for planning treatment and predicting prognosis. Therefore, genetic testing is essential in these patients.This article is freely available online. Click on the 'Additional Link' above to access the full-text via the publisher's site.Unknow

Molecular Diagnosis of Monogenic Diabetes and Clinical/Laboratory Features in Turkish Children

Objective: Monogenic diabetes is a heterogeneous disease that causes functional problems in pancreatic beta cells and hyperglycemia. The aim of this study was to determine the clinical and laboratory features, the admission characteristics and distribution of monogenic form of diabetes in childhood in Turkey. Methods: Patients aged 0-18 years, who were molecularly diagnosed with monogenic diabetes, and consented to participate, were included in the study. Results: Seventy-seven (45.6%) female and 92 male cases with a mean age of 8.18 +/- 5.05 years at diagnosis were included. 52.7% of the cases were diagnosed with monogenic diabetes by random blood glucose measurement. The reason for genetic analysis in 95 (56.2%) of cases was having a family member diagnosed with diabetes under the age of 25. At the time of diagnosis, ketone was detected in urine in 16.6% of the cases. Mean hemoglobin A1c on admission, fasting blood glucose, fasting insulin, and c-peptide values were 7.3 +/- 2.1%, 184.9 +/- 128.9 mg/dL, 9.4 +/- 22.9 IU/L, 1.36 +/- 1.1 and ng/L respectively. GCK-MODY was found in 100 (59.2%), HNF1A-MODY in 31 (18.3%), and variants in ABCC8 in 6 (3.6%), KCNJ11 in 5 (3%), HNF4A in 2 (1.2%), and HNF1B in 2 (1.2%). Conclusion: Recent studies have indicated HNF1A-MODY is the most frequent of all the MODY-monogenic diabetes cases in the literature (50%), while GCK-MODY is the second most frequent (32%). In contrast to these reports, in our study, the most common form was GCK-MODY while less than 20% of cases were diagnosed with HNF1A-MODY