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.

METAP1 mutation is a novel candidate for autosomal recessive intellectual disability.

Intellectual disability (ID) is a genetic and clinically heterogeneous common disease and underlying molecular pathogenesis can frequently not be identified by whole-exome/genome testing. Here, we report four siblings born to a consanguineous union who presented with intellectual disability and discuss the METAP1 pathway as a novel etiology of ID. Genomic analyses demonstrated that patients harbor a novel homozygous nonsense mutation in the gene METAP1. METAP1 codes for methionine aminopeptidase 1 (MetAP1) which oversees the co-translational excision of the first methionine remnants in eukaryotes. The loss-of-function mutations to this gene may result in a defect in the translation of many essential proteins within a cell. Improper neuronal function resulting from this loss of essential proteins could lead to neurologic impairment and ID.

Does Covid-19 in children have a milder course than Influenza?

BACKGROUND: In December 2019, a novel type of coronavirus infection emerged in the Wuhan province of China and began to spread rapidly. In this study, we aimed to determine the differences between COVID-19 disease and Influenza. METHODS: This retrospective study included 164 children with COVID-19, as well as 46 children with Influenza. The two groups were compared with respect to clinical and laboratory parameters and the rates of intensive care and mechanical ventilation requirement. RESULTS: In both groups, the most common admission complaints were fever and cough. As compared to the COVID-19 group, the Influenza group had significantly higher rates of cough (37 [80.4%] and 38 [23.2%]), fever (31 [67.4%] and 34 [20.7%]), muscle pain (34 [73.9%] and 31 [18.9%]), vomiting (13 [28.9%] and 8 [4.9%]) and tachypnea (32 [69.6%] and 3 [1.8%]) (P < .01 for all comparisons). The mean WBC count (7.10 ± 1.08 vs. 10.90 ± 1.82), mean neutrophil count (3.19 ± 0.58 vs. 6.04 ± 0.97), APTT, CRP, procalcitonin, ALT, and LDH levels were significantly lower in the COVID-19 group compared to the Influenza group (P < .05 for all comparisons). There was, however, no significant difference between the mean lymphocyte counts of both groups. The Influenza group had significantly higher rates of intensive care requirement (19 [41.3%] vs. 3 [1.8%]) and mechanical ventilation requirement (16 [34.8%] vs. 2 [1.2%]) as well as a significantly higher mortality rate (7 [15.2%] vs. 2 [1.2%]) than the COVID-19 group (P < .01). CONCLUSION: COVID-19 and Influenza may share similar clinical features. According to our findings, however, we believe that COVID-19 disease has a milder clinical and laboratory course than Influenza in children.

Urinary kidney injury molecules in children with febrile seizures.

OBJECTIVE: Hypoxia occurs following convulsions, and hypoxia is one of the most common causes of acute renal damage. The aim of this study was to investigate urinary levels of kidney injury molecules, including neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-ß-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with febrile seizures (FS) for the first time. METHODS: The study included 28 children with FS and 34 age and gender matched healthy children. Serum biochemistry and blood gases were measured in the serum samples. Estimated glomerular filtration rate (eGFR) was calculated. NGAL, NAG, L-FABP, and creatinine (Cr) were measured in the urine samples. The ratios of kidney injury markers to urinary Cr were used for comparisons. RESULTS: There were no significant differences in eGFR and serum chemistry values between the FS and the control group (p > 0.05). Hypoxia was detected in 67.9% of the FS patients. The FS group had significantly higher urinary kidney injury molecules to Cr ratios compared to the controls, including NGAL/Cr (17.9 ± 9.8; 6.7 ± 4.0, respectively; p < 0.001), NAG/Cr (0.55 ± 0.29; 0.21 ± 0.16, p < 0.001), and L-FABP/Cr (4.85 ± 2.93; 1.74 ± 1.16, p < 0.001). CONCLUSION: Increased urinary NGAL/Cr, NAG/Cr, and L-FABP/Cr values, in patients with FS compared to healthy controls, suggest a possible subclinical renal damage in these patients.

Serum galectin-3 levels in children with chronic hepatitis B infection and inactive hepatitis B carriers.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is common worldwide. Follow-up of patients by the use of non-invasive techniques may be valuable in clinical practice. The aim of this study was to investigate serum galectin-3 (GAL-3) levels for monitoring disease status in children with chronic HBV infection. MATERIAL/METHODS: Thirty-two patients with chronic hepatitis B (CHB), 30 inactive HBV carrier patients, and 30 matched healthy controls were enrolled in the study. We performed basic laboratory tests: serum glucose, albumin, alanine aminotransferase (ALT), aspartate aminotransferase, gamma-glutamyl transferase (GGT), total bilirubin, prothrombin time, and activated partial thromboplastin time. In addition, serum GAL-3 levels were measured by ELISA technique. RESULTS: Significantly higher serum GAL-3 levels (16.5±3.6, 1.1±0.3, 0.7±0.5 ng/ml, respectively, p<0.001) and ALT levels (80.2±30.6, 26.8±12.6, 28.1±4.4 IU/L, respectively, p<0.001) were found in the CHB group compared with the inactive carriers and the control groups. There were no significant differences in ALT levels and GAL-3 levels or between inactive HBV carriers and the control groups (p>0.05, for each). Significantly higher GGT levels were found in the CHB group (51.3±27.5 IU/L) compared with the inactive HBV carriers (35.7±10.1 IU/L) and the control group (31.3±9.5 IU/L) (p<0.001, and p=0.004, respectively). A significant correlation was found between GAL-3 and ALT levels in the CHB group (r=0.82, p<0.001). CONCLUSIONS: Our results suggest that serum GAL-3 level may be a beneficial indicator of chronicity in hepatitis B infection in children.

Urinary Kidney Injury Molecules in Children with Iron-Deficiency Anemia.

BACKGROUND: The aim of this study was to investigate the urine levels of human kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-ß-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with iron-deficiency anemia (IDA). MATERIAL AND METHODS: Thirty-five children with IDA and 32 matched healthy controls were recruited. We assessed complete blood count, serum iron, iron-binding capacity, ferritin, serum levels of urea, creatinine (Cr), sodium (Na), potassium (K), calcium (Ca), and glucose levels. Estimated glomerular filtration rate (eGFR) was calculated. Urinary NAG, NGAL, KIM-1, and L-FABP were measured and divided by urine creatinine for comparisons. RESULTS: There were no significant differences in serum urea, Cr, or eGFR between the IDA group and the control group (p>0.05, for all). IDA patients had significantly higher urine NGAL/Cr, L-FABP/Cr, KIM-1/Cr, and NAG/Cr compared with the control group (p<0.05). There were significant negative correlations between hemoglobin, hematocrit, red blood cell count, and urine NGAL/Cr, NAG/Cr, L-FABP/Cr, KIM-1/Cr levels (p<0.05). CONCLUSIONS: Higher urinary kidney injury molecule levels in IDA patients suggest a possible subclinical renal injury in pediatric IDA patients whose renal functions and serum electrolytes were normal.

First year real life experience with tenofovir alafenamide fumarate: The pythagorean cohort.

Background and Aim: In chronic hepatitis B infection, antiviral therapy significantly reduces the incidence of complications. This study aimed to present real-life 12-month effectiveness and safety data for TAF. Materials and Methods: This Pythagoras Retrospective Cohort Study included patients from 14 centers in Turkiye. The study presents 12-month results of 480 patients treated with TAF as initial therapy or after switching from another antiviral drug. Results: The study shows treatment of about 78.1% patients with at least one antiviral agent (90.6% tenofovir disoproxil [TDF]). The rate of undetectable HBV DNA increased in both treatment-experienced and naive patients. In TDF-experienced patients, the rate of alanine transaminase (ALT) normalization increased slightly (1.6%) within 12 months, but the change was not statistically significant (p=0.766). Younger age, low albumin, and high body mass index and cholesterol were identified as risk factors for abnormal ALT after 12 months, but no linear relationship was detected. In TDF-experienced patients, renal and bone function indicators showed significant improvement three months after the transition to TAF and remained stable for 12 months. Conclusion: Real-life data demonstrated effective virological and biochemical responses with TAF therapy. After switching to TAF treatment, gains in kidney and bone functions were achieved in the early period.

Retrospective Evaluation of Patients With Scorpion Stings Admitted to the Pediatric Emergency Clinic.

Introduction Scorpion sting in children is still a serious health problem today. Children are at greater risk of developing severe cardiac, respiratory, and neurological complications because of their low body weight. In this study, we retrospectively evaluated the demographical changes, complaints, clinical findings, and laboratory results of scorpion sting cases admitted to the pediatric emergency department.  Materials and Methods The records of 72 patients who were followed up with the diagnosis of scorpion sting in the Dicle University Pediatric Emergency Department between 2013 and 2017 were retrospectively analyzed. Results The patients included in the study were between one and 15 years (7.64±4.04 years) and 43.1% were male, and 56.9% were female. While 65.3% of the cases lived in rural areas, 34.7% lived in the city center. The most common stung areas in the cases were the lower extremity (51.4%) and the upper extremity (34.7%). The most common complaints in the patients were 70.8% pain, 58.3% edema, 41.7% cold extremities, 23.6% sweating, 22.2% vomiting, and 12.5% excessive salivation. Of the cases, 71.4% had mild, 25.7% had moderate, and 2.9% had severe stages. Of the patients, 91.6% were given antivenom, 75.7% were given antihistamines, 74.3% were given steroids, 65.7% were given antibiotics, 64.3% were given analgesics, 44.3% were given tetanus vaccine, 2.8% were given erythrocyte suspension and 1.4% were given platelet suspension. In addition, 11.4% of the cases were given prazosin treatment. While 32.9% of the cases required intensive care, two patients died. A statistically significant difference was found between the glucose, urea, creatine, total protein, sodium, potassium, alanine aminotransferase, white blood cell count, red blood cell count, hemoglobin, hematocrit, neutrophil count values of the patients at admission and discharge. Conclusion Scorpion sting cases are still a significant health problem. The severe clinical course is more common in children. The management of patients with severe clinical forms is based on early recognition of the sting, antivenom serum administration, and cardiorespiratory and systemic support.

Evaluation of inflammatory and hematological parameters in patients diagnosed with COVID-19.

INTRODUCTION: This study aims to research the effects of hematological and inflammatory parameters on the prognosis of COVID-19 disease and hospitalization duration. METHODOLOGY: One hundred and eighty-six patients with COVID-19 and a control group consisting of 187 healthy individuals were included in the study. Hematological variables and inflammatory parameters of the patients were recorded on the first and the fifth days of hospitalization. RESULTS: White blood cell count, lymphocyte count, and platelet count were statistically lower, and mean platelet volume (MPV), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) levels were higher in the patient group compared to the control group. It was observed that the neutrophil count and MPV level were lower, and the platelet count and ferritin level were statistically higher on the fifth day of follow-up compared to the admission day. In contrast, there was a significantly positive correlation between the duration of hospitalization and the fifth day D-dimer (r = 0.546, p < 0.001) and ferritin (r = 0.568, p < 0.001); in addition, there was a negative correlation between the duration of hospitalization and admission day lymphocyte count and the fifth-day lymphocyte count. CONCLUSIONS: Increased levels of ferritin and D-dimer, and decreased count of lymphocytes are among the important factors affecting the duration of hospitalization for COVID-19 patients. Furthermore, we think that neutrophil count and MPV levels are low, and platelet count and ferritin levels are high during the disease. Therefore, these parameters can be used as prognostic indicators of the disease.

Evaluation of Hematological Parameters of Children Diagnosed with COVID-19: Single-Center Experience.

OBJECTIVE: Although many pediatric studies on children infected with coronavirus disease 2019 (COVID-19) have been published, the diagnosis, clinical symptoms, laboratory findings, and treatment of COVID-19 in children are still unclear. MATERIALS AND METHODS: This study was conducted with an aim to examine the hematological findings of symptomatic pediatric patients diagnosed with COVID-19 in May 2020 at the Pandemic Hospital in Dicle University. Patient records were evaluated retrospectively. This study involved 59 symptomatic pediatric patients with a definite diagnosis of COVID-19 who had positive SARS-CoV-2 RT-PCR test results on nasopharyngeal swab between March 15, 2020 and May 31, 2020. RESULTS: The records of a total of 10 (16.9%) patients under the age of 1; 21 (35.6%) patients aged 1-10 years, and, 28 (47.5%) patients aged 10-18 years, who had been diagnosed with COVID-19 were evaluated. Based on severity, 35 (59.3%) patients were in the mild group (group 1) and 24 (40.7%) patients were in the moderate-severe group (group 2). The blood parameters of WBC, neutrophil, lymphocyte, monocyte, and thrombocyte counts, the hemoglobin (Hgb) level, and NLR, PLR, MPV, fibrinogen, ferritin, and D-dimer levels were compared between groups, the difference was not statistically significant (P > .05). LDH was higher in group 2 (P = .014). CONCLUSION: Since children infected with COVID-19 show mild clinical symptoms or are asymptomatic, fewer pediatric patients may be detected than adults. Therefore, it should be known that the laboratory findings typical for adults may not accompany the disease in pediatric cases. More studies are needed to determine the most appropriate COVID-19 treatment approach for children, as hospitalization history and testing rates are less reported among children.

Comparison of Inflammatory Markers between Adult and Pediatric Brucellosis Patients.

INTRODUCTION: This study aimed to evaluate and compare with healthy control subjects the levels of indirect inflammatory markers such as mean platelet volume (MPV), platelet to lymphocyte ratio (PLR), and neutrophil to lymphocyte ratio (NLR) in adults and children with brucellosis. METHODS: White blood cell, neutrophil, lymphocyte, and platelet counts, and C-reactive protein (CRP) levels were retrospectively recorded for all participants. RESULTS: NLR and neutrophil counts were significantly higher in adult patients compared to those in pediatric patients. CONCLUSIONS: Indirect inflammatory markers such as NLR, PLR, MPV, red distribution width, and CRP levels may be helpful for follow-up of brucellosis.

Evaluation of the novel coronavirus disease in Turkish children: Preliminary outcomes.

BACKGROUND: The novel coronavirus disease (Covid-19) can progress with mild to moderate or self-limiting clinical findings in children. The aim of this study was to investigate the disease features of Covid-19 in Turkish children. METHODS: Children diagnosed by the method of real-time reverse transcription-polymerase chain reaction for Covid-19 at the Dicle University Department of Pediatric, between April and June 2020, were evaluated. Hospital records were investigated retrospectively. RESULTS: One hundred and five patients children with the mean age of 108.64 ± 65.61 months were enrolled in this study. The most common cause of transmission in pediatric patients was in contact with a family member diagnosed with COVID-19 (n = 91, 86.7%). The most common admission complaints were dry cough (n = 17, 16.2%), fever (n = 16, 15.2%), lassitude and fatigue (n = 14, 13.3%) respectively. More than 95% of all children with Covid-19 were asymptomatic, mild, or moderate cases. CRP was identified only independent factor associated with long duration of hospitalization. CONCLUSION: The results of this study show the effect of Covid-19 on Turkish children. A clear understanding of the local epidemiology of corona virus infections and identification of risk factors are critical for the successful implementation of the prevention and control program.

Multicenter Hospital-Based Prospective Surveillance Study of Bacterial Agents Causing Meningitis and Seroprevalence of Different Serogroups of Neisseria meningitidis, Haemophilus influenzae Type b, and Streptococcus pneumoniae during 2015 to 2018 in Turkey.

The etiology of bacterial meningitis in Turkey changed after the implementation of conjugated vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) in the Turkish National Immunization Program (NIP). Administration of Hib vaccine and PCV-7 (7-valent pneumococcal conjugate vaccine) was implemented in NIP in 2006 and 2009, respectively. In 2011, PCV-7 was replaced with PCV-13. Meningococcal vaccines have not yet been included in Turkish NIP. This prospective study comprised 27 hospitals located in seven regions of Turkey and represented 45% of the population. Children aged between 1 month and 18 years who were hospitalized with suspected meningitis were included. Cerebrospinal fluid (CSF) samples were collected, and bacterial identification was made according to the multiplex PCR assay results. During the study period, 994 children were hospitalized for suspected meningitis, and Hib (n = 3, 2.4%), S. pneumoniae (n = 33, 26.4%), and Neisseria meningitidis (n = 89, 71%) were detected in 125 samples. The most common meningococcal serogroup was MenB. Serogroup W comprised 13.9% (n = 5) and 7.5% (n = 4) of the meningococci in 2015 to 2016 and 2017 to 2018, respectively. Serogroup C was not detected. There were four deaths in the study; one was a pneumococcus case, and the others were serogroup B meningococcus cases. The epidemiology of meningococcal diseases has varied over time in Turkey. Differing from the previous surveillance periods, MenB was the most common serogroup in the 2015-to-2018 period. Meningococcal epidemiology is so dynamic that, for vaccination policies, close monitoring is crucial.IMPORTANCE Acute bacterial meningitis (ABM) is one of the most common life-threatening infections in children. The incidence and prevalence of ABM vary both geographically and temporally; therefore, surveillance systems are necessary to determine the accurate burden of ABM. The Turkish Meningitis Surveillance Group has been performing a hospital-based meningitis surveillance study since 2005 across several regions in Turkey. Meningococcus was the major ABM-causing agent during the 2015-to-2018 period, during which MenB was the dominant serogroup.

Importance of pedigree in patients with familial epilepsy and intellectual disability.

In this study, we prospectively evaluated demographic characteristics, clinical findings and pedigree patterns in 70 patients with familial epilepsy and/or intellectual disability (ID)/global developmental delay (GDD) and/or motor retardation but without specific etiologic diagnosis to determine genetic inheritance patterns by using at least a three-generation pedigree analysis. Mean age of the patients was 6.85 ± 3.93 years and male/female ratio was 1.50. There was consanguinity between the parents of 47 (67.1%) patients. Only epilepsy was diagnosed in 14 patients; only ID/GDD in 22; epilepsy and ID/GDD in 9 and epilepsy and ID/GDD and motor retardation in 25 patients. Genetic inheritance pattern was definitely determined in 60 (85.7%) patients, and most of the patients (61.4%) displayed autosomal recessive inheritance. Based on our findings, we suggest that a three-generation pedigree analysis should be obtained in all patients with familial neurological disorders, including epilepsy, ID/GDD and motor retardation, to optimise counselling, screening and diagnostic testing.

Mean platelet volume, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in determining the diagnosis or outcome in children with snakebite. / Volumen plaquetario medio, índice de neutrófilos/linfocitos e índice de trombocitos/linfocitos para determinar el diagnóstico y/o pronóstico en niños con mordedura de serpiente.

BACKGROND: The objective of this study is to evaluate the relationships between the mean platelet volume (MPV), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) variables and diagnosis or prediction of outcome in children with snakebite envenomation. METHODS: Children diagnosed with snakebite envenomation and a control group of healthy subjects were retrospectively evaluated. Patients were classified into three groups as mild, moderate and severe. RESULTS: 142 children were enrolled in the study. Leukocytosis (p= 0.003), neutrophilia (p= 0.026) and thrombocytopenia (p= 0.034) were significantly more common in severe snakebite envenomation, although no statistical significant were found in association with MPV, NLR and PLR between snakebite envenomation groups. The mean MPV, NLR and PLR were found to be significantly higher in children with snakebite compared to than among healthy controls. CONCLUSIONS: Our results suggested that MPV, NLR and PLR may be useful for the diagnosis as inflammatory markers in snakebite envenomation.

OBJETIVO: Evaluar la relación entre las variables de volumen plaquetario medio (VPM), índice de neutrófilos/linfocitos (INL) e índice de trombocitos/linfocitos (ITL) y el diagnóstico o la predicción del desenlace en los niños con intoxicación por mordedura de serpiente. MÉTODOS: Se realizó una evaluación retrospectiva de niños con diagnóstico de intoxicación por mordedura de serpiente y un grupo de referencia de sujetos sanos. Se clasificó a los pacientes en tres grupos de intoxicación: leve, moderada y grave. CONCLUSIONS: Según nuestros resultados, el uso del VPM, el INL y el ITL podría servir para el diagnóstico como marcadores inflamatorios en los casos de intoxicación por mordedura de serpiente.

Colistin use in critically ill neonates: A case-control study.

BACKGROUND: The aim of this study was to assess the safety and efficacy of colistin use in critically ill neonates. METHODS: This was a case-control study that included newborn infants with proven or suspected nosocomial infections between January 2012 and October 2015, at two centers in Diyarbakir, Turkey. The clinical and laboratory characteristics and outcomes of patients who received colistin therapy were reviewed and compared to patients who were treated with antimicrobial agents other than colistin during the same period. RESULTS: Forty-seven cases who received intravenous colistin (colistin group) and 59 control patients (control group) were included. There were no significant differences between the groups regarding outcomes and nephrotoxicity, including acute renal failure. Colistin therapy was associated with significantly reduced serum magnesium (1.38 ± 0.39 mg/dL vs. 1.96 ± 0.39 mg/dL, p < 0.001) and hypokalemia (46.8% vs. 25.4%, p = 0.026). The patients who received colistin also had longer hospital stays (43 (32-70) days vs. 39 (28-55) days, p = 0.047), a higher rate of previous carbapenem exposure (40.4% vs. 11.9%, p = 0.001), and a higher age at the onset of infection (13 (10-21) days vs. 11 (9-15) days, p = 0.03). CONCLUSION: This study showed that colistin was both effective and safe for treating neonatal infections caused by multidrug-resistant gram-negative bacteria. However, intravenous colistin use was significantly associated with hypomagnesemia and hypokalemia.