Ulaş Emre Akbulut

Early Clinical Diagnosis of PC1/3 Deficiency in a Patient With a Novel Homozygous PCSK1 Splice-Site Mutation.

ABSTRACT Autosomal recessive proprotein convertase 1/3 (PC1/3) deficiency, caused by mutations in the PCSK1 gene, is characterized by severe congenital malabsorptive diarrhea, early-onset obesity, and certain endocrine abnormalities. We suspected PC1/3 deficiency in a 4-month-old girl based on the presence of congenital diarrhea and polyuria. Sequencing the whole coding region and splice sites detected a novel homozygous PCSK1 splice-site mutation, c.544–2A>G, in the patient. The mutation resulted in the skipping of exon 5, the generation of a premature termination codon, and nonsense-mediated PCSK1 messenger ribonucleic acid decay, which was demonstrated in complementary DNA derived from fibroblasts.

Association between Adherence to the Mediterranean Diet and Presence of Nonalcoholic Fatty Liver Disease in Children

OBJECTIVE The studys objective was to analyze the association between the adherence to the Mediterranean diet (MD) and the presence of nonalcoholic fatty liver disease (NAFLD) in children. METHODS The study consisted of three groups of children. Group 1 included obese/overweight children with recent diagnosis of NAFLD (n = 106, 12.4 ± 2.6 years). Group 2 included obese children without NAFLD (n = 21, 11.3 ± 2.6 years). Group 3 included the healthy children (without known chronic disease) with normal BMI (n = 54, 11.8 ± 2.9 years). Compliance to the MD was assessed by the KIDMED index score. RESULTS KIDMED index score in obese children with NAFLD, without NAFLD, and healthy children were 2.6 ± 2.4, 4.6 ± 1.2, and 6.2 ± 1.9, respectively (p < 0.05 for group 1 versus 2, 1 versus 3, and 2 versus 3). Diet compliance was good in only 4.7% of the patients with NAFLD, whereas it was 31.5% in healthy children. KIDMED index score was negatively correlated with BMI (p < 0.05, r = -0.53), but no correlation was found with other parameters. The area under the receiver operation curve (AUROC) for predicting fatty liver disease in obese children (n = 127) with BMI and KIDMED index score was 0.78 (p < 0.05) and 0.24 (p < 0.05), respectively. BMI >26 has a sensitivity of 79.2% and specificity of 52.4%, and KIDMED index score ≤3 has a sensitivity of 66.9% and specificity of 76.1%. CONCLUSIONS MD is an inexpensive and nontoxic dietary regimen and may be used as a therapeutic option in obese children with NAFLD.

Efficacy and Safety of Low Dose Ketamine and Midazolam Combination for Diagnostic Upper Gastrointestinal Endoscopy in Children

Purpose We aimed to analyze the effectiveness and safety of low-dose midazolam and ketamine combination for upper gastrointestinal endoscopy (UGIE) in children. Methods The study included the children (n=425, 10.78±3.81 years) who underwent UGIE for diagnostic purpose during 1 year period. All children were sedated with low dose midazolam (0.1 mg/kg) and ketamine (0.5 mg/kg) intravenously. Effectiveness of the sedation and complications during the procedure and recovery period were recorded. Results Endoscopic procedure was successfully completed in 414 patients (97.4%; 95% confidence interval, 95.8-98.9). Mean±standard deviation (SD) duration of procedure was 6.36±1.64 minutes (median, 6.0 minutes; range, 4-12 minutes). Minor complications occurred during the procedure in 39.2% of the patients. The most common complication was increased oral secretion (33.1%). No major complications were observed in any patient. Age and Ramsay sedation scores of patients with complications during the procedure were lower than the others (9.49±4.05 years vs. 11.61±3.43 years, p=0.002 and 2.10±1.46 vs. 4.37±1.16, p=0.001). Mean recovery time was 22 minutes (range, 10-90 minutes; mean±SD, 25±12.32 minutes). Minor complications developed during recovery in 60.1% of the patients. The most common complication was transient double vision (n=127, 30.7%). Emergence reaction was observed in 5 patients (1.2%). Conclusion The procedure was completed with high level of success without any major complication in our study. Combination of low-dose midazolam and ketamine is a suitable sedation protocol for pediatric endoscopists in UGIE.

A comparison of sedation with midazolam-ketamine versus propofol-fentanyl during endoscopy in children: a randomized trial.

Purpose We aimed to compare the efficacy and safety of midazolam plus ketamine versus fentanyl plus propofol combination administered to children undergoing upper gastrointestinal endoscopy (UGE) and to determine the most appropriate sedation protocol. Materials and methods This prospective, randomized, single-blind study included patients between the ages of 4 and 17 years who underwent UGE for diagnostic purposes. Patients were divided randomly into groups A (midazolam–ketamine combination, n=119) and B (fentanyl plus propofol combination, n=119). The effectiveness of the sedation and complications during the procedure and recovery period were recorded. Results The processes started without an additional dose of the drug for 118 patients (99.1%) in group A and for 101 patients (84.8%) in group B (P=0.001). The average dose of ketamine administered to the patients in group A was 1.03±0.15 mg/kg and the average dose of propofol administered to the patients in group B was 1.46±0.55 mg/kg. None of the patients stopped the endoscopic procedure in group A, but one patient (0.8%) had to discontinue the endoscopic procedure in group B. 27 patients in group A (22.7%) and 41 patients (34.5%) in group B developed complications during the procedure (P=0.044). The rate of complications during the recovery of group A (110 patients, 92.4%) was significantly higher than that in group B (48 patients, 40.3%) (P=0.001). Conclusion In children, UGE procedures can be quite comfortable when using the midazolam–ketamine combination. However, adverse effects related to ketamine were observed during recovery.

The coexistence of neurofibromatosis type I and celiac disease in a child

A 12-year-old girl who had neurofibromatosis type 1 (NF1) for 6 years presented to a pediatric gastroenterology clinic with the complaint of short stature. She was the third child of non-consanguineous parents. Her older brother had been also diagnosed with NF1. Her physical examination revealed that her weight was 33 kg (3-10 percentile) and that her height was 139 cm (<3 percentile, Z score: -2.2). There were multiple cafe au lait spots on her skin; the largest one was 5×5 cm in diameter. Her ophthalmological examination revealed the presence of Lisch nodules on her iris. There were no pathological findings found in her brain and on performing orbital magnetic resonance imaging and abdominal ultrasonography. While her complete blood count; liver and kidney function test results; and electrolyte, basal growth hormone, free thyroxine (T4), free triiodothyronine (T3), thyrotropin-stimulating hormone, serum ferritin, folate, and total IgA levels were normal, her vitamin B12 and vitamin D3 levels were low. After positive serum anti-endomysial IgA level, upper gastrointestinal endoscopy was performed. A mosaic pattern was observed at the second portion of the duodenum, and her histopathological examination results were compatible with Marsh 3B. The patient with positive human leucocyte antigen (HLA) DQ2 was diagnosed as having celiac disease (CD), and a gluten-free diet (GFD) was introduced. At the 9th month of introducing the GFD, negative antiendomysial IgA levels were observed, with a significant increase in the patient’s height and weight.

Esophageal eosinophilia in children: a 6-year single-center experience

Çakır M, Sağ E, Mungan S, Akbulut UE, Orhan F. Esophageal eosinophilia in children: A 6-year single-center experience. Turk J Pediatr 2017; 59: 369-378. Esophageal eosinophilia (EE) and eosinophilic esophagitis (EoE) are emerging clinical entities, the prevalence of which has increased during the last 15 years. However, there is a lack of data concerning the etiology and outcomes of EE in children. The aim of this study was therefore to analyze the clinical findings and outcomes of children with EE and EoE in our pediatric gastroenterology unit over a 6-year period. The study included children undergoing esophagogastroduodenoscopy (EGD) during this 6-year period (January 2010 to December 2015) in our pediatric gastroenterology unit. The files of patients with EE were re-evaluated in detail to elicit demographic features, clinical, laboratory and histopathological findings, treatment modalities and outcomes. EE was determined in 33 patients [0.95% (95% CI: 0.63-1.27) among all children, and in 4.66% (95% CI: 3.11-6.21) of children undergoing esophageal biopsy] (8.6±4.2 years and 72.7% male). EoE was the most common cause of EE (n=11, 33.3%), followed by eosinophilic gastroenteropathy (n=6, 18.1%) and proton pump inhibitor responsive esophageal eosinophilia (n=4, 12.1%). Patients with EoE (n=11) were followed up for 21.2±18 (range: 1-60) months, and treatment was discontinued in 2 patients (18.1%). Additionally, 5 patients (45.5%) received diet elimination only and 1 patient (9%) received a combination of low dose steroids and diet. Three patients (27.2%) are still being treated under the initial regimen. The overall incidence of EE increased in 2014-2015 compared to 2010-2011 (0.41% vs. 1.33, p=0.047, OR: 3.22 and 95% CI: 0.94-10.98, p=0.06). EE is an increasingly common clinical entity with a wide spectrum of etiology and clinical presentations in children.

Interleukin-6 and interleukin-17 gene polymorphism association with celiac disease in children

BACKGROUND/AIMS This study aimed to investigate polymorphisms in the genes responsible for encoding cytokines interleukin-6 (IL-6) (-572G/C) (rs1800796) and IL-17 (-197A/G) (rs2275913) in patients with celiac disease (CD). We further aimed to investigate the relationship between CD symptoms and histopathological findings and the relationship between these polymorphisms. MATERIALS AND METHODS We compared the results with those of healthy control subjects to establish whether any of the polymorphisms are involved in the susceptibility to CD. Eighty-four patients with CD and 83 healthy controls were enrolled in this study. Children with CD were divided into two groups depending on whether their symptoms were typical or atypical. The IL-6 (-572G/C) and IL-17 (-197A/G) polymorphisms were genotyped based on a polymerase chain reaction coupled with restriction fragment length polymorphism. RESULTS Significant differences for the IL-6 (-572G/C) polymorphism were observed between patients with CD and controls (p=0.018, odds ratio (OR): 5.47, 95% confidence interval (CI): 1.161-25.800). No statistically significant association was observed between the IL-17 (-197A/G) polymorphism and CD (p>0.05). In addition, the symptoms and histopathological findings of children with CD were not related to either of the polymorphisms. CONCLUSION The results of our study indicate that the IL-6 (-572G/C) polymorphism may play a role in susceptibility to CD.

Long-term prognosis of chronic hepatitis B virus infection in the childhood.

AIM It was aimed to investigate the modes of transmisson and long-term prognosis of the disease in patients who were followed up with a diagnosis of chronic hepatitis B infection. MATERIAL AND METHODS The files of the patients who presented to our outpatient clinic between January 2002 and May 2013 and were being followed up with a diagnosis of chronic hepatitis B virus infection were examined retrospectively and the information related with the age, gender, age at the time of diagnosis, mode of transmission, follow-up period, transaminase levels, the amount of hepatitis B virus-deoxyribonucleic acid and treatment and responses to the treatment given were recorded. RESULTS The age at the time of diagnosis of 150 patients (97 males, 64%) included in the study was 14.95±2.94 years. 59 (39.3%) of the patients were inactive carriers, 61 (40.7%) were in the immunotolerant stage and 30 (20%) were in the immunoreactive stage. Vertical transmission was present in 86 (57.3%) patients, horizontal transmission was present in 41 patients (27.3%) and the mode of transmission was not known in 23 patients (15.3%). Response to treatment was obtained in 26 (72.2%) of 36 patients who received treatment. Lamivudine (4 mg/kg/day) was given to 29 of the patients who were given treatment, interferon-α (IFN-α) (6 MU/m(2), three days a week) was given to 3 patients at the same dose and both IFN-α and lamivudine were given to 4 patients. The time to give response to treatment was 24.23±15.23 months (6-50 months). Spontaneous anti-HBe seroconversion occured in four (7.2%) of 55 immuntolerant children who were followed up without treatment. The time to development of seroconversion in these children was 2.50±1.91 years (1-5 years). CONCLUSIONS Chronic hepatitis B virus infection has a more benign prognosis in children compared to adults, though it may lead to development of hepatic failure, cirrhosis and hepatocellular cancer. In addition, a decrease in the frequency of infection is expected in children in the years ahead owing to vaccination programs. However, we think that studies related with use of different drugs in patients who do not respond to treatment should be performed.