A Neurological Appearance of Celiac Disease: Is There Any Associated Factor?

OBJECTIVE: Celiac disease may present with one or more neurological signs and/or symptoms. We aimed to define the incidence of accompanying neurological manifestations in children diagnosed as having celiac disease. METHODS: The prospective study included 146 children diagnosed as having celiac disease. The medical records (presentation symptoms, clinical findings, serological test, duodenal biopsy results, lack/deficiency of vitamin, tissue type, accompanying autoimmune disorders) and demographic data of all patients were also reviewed. RESULTS: Thirty-five (23.9%) of the 146 celiac patients exhibited one or more neurological findings. Headache (11.6%) and dizziness (6.1%) were the most common symptoms among neurological manifestations. There was a significant difference between the patients with and without neurological manifestations in terms of sex, biopsy result, and tissue type (P < 0.05). Moreover, there was a statistically significant difference between tissue types of the patients with and without headache (P < 0.05). We found that grade 3a by Marsh classification was the most common type among the patients with and without neurological findings in celiac disease. On neuroimaging evaluation of patients, 1 patient with chronic focal ischemic lesion, 1 patient with Chiari type 1 malformation, and 1 patient with subcortical white matter changes were identified. CONCLUSIONS: Pathophysiology of neurological involvement in celiac disease is liable for various neurological findings. This study contributes to data suggesting that female sex, mild histopathological form, and human leukocyte antigen DQ2 heterozygosity are related to neurological manifestations, and also human leukocyte antigen DQ2 heterozygosity is associated with headache in celiac disease.

Increased zonulin is associated with hyperactivity and social dysfunctions in children with attention deficit hyperactivity disorder.

BACKGROUND: In attention deficit hyperactivity disorder (ADHD), deteriorations of brain gut axis has been shown in previous studies. One area where the most important challenges are seen in ADHD is social functioning. Zonulin is a protein found in the intestinal intraepithelial component; it has been shown that the level of zonulin increases when intestinal permeability is impaired. Changes in intestinal function were shown in ADHD. Zonulin has been shown to be associated with social impairment in children with autism spectrum disorder. In this study, it was aimed to evaluate the relationship between the ADHD symptoms and zonulin in children with ADHD. Secondarily relation of zonulin and difficulties in social functioning was examined in these children. METHODS: Forty children diagnosed with ADHD and forty-one healthy children similar age and gender to ADHD group and their mothers were included in the study. Children without any chronic systemic immunological or infectious diseases were included in the case and control group. The ADHD symptoms were scored by the DuPaul ADHD scale and the social functioning of the children was assessed by the Social Responsiveness Scale (SRS). Serum zonulin levels were analyzed by enzyme-linked immunosorbent assay. RESULTS: Children with ADHD had higher serum zonulin levels and were more impaired in social functioning compared to controls. The level of zonulin was independently predicted with hyperactivity symptoms and SRS scores in regression analysis. CONCLUSION: In this sample of children with ADHD, elevated zonulin levels were associated with increased symptoms of hyperactivity and impairment of social functioning.

Bullous skin lesions in a jaundiced infant after phototherapy: a case of congenital erythropoietic porphyria.

Congenital erythropoietic porphyria is a rare autosomal recessive disorder of porphyrin metabolism in which the genetic defect is the deficiency of uroporphyrinogen III cosynthase (UIIIC). Deficiency of this enzyme results in an accumulation of high amounts of uroporphyrin I in all tissues, leading to hemolytic anemia, splenomegaly, erythrodontia, bone fragility, exquisite photosensitivity, and mutilating skin lesions. We discuss a female infantile case who was admitted for jaundice; bullous lesions appeared on her trunk during phototherapy in the neonatal period. The skin biopsy findings were consistent with epidermolysis bullosa. Due to persistent hepatosplenomegaly and cholestasis, metabolic tests and liver biopsy were performed. During the follow-up, hemolytic anemia and red urine were detected. The levels of porphyrin metabolites were determined at high concentrations in plasma, stool and urine analysis, which were suggestive of congenital erythropoietic porphyria.

The Results of Pneumatic Balloon Dilatation Treatment in Children with Achalasia: A Single-Center Experience.

BACKGROUND/AIMS: Achalasia is a primary motility disorder characterized by a relaxation disorder of the lower esophageal sphincter. In pneumatic balloon dilatation, which is one of the treatment methods, the muscle fibers are torn with an endoscopically inflated balloon in the lower esophageal sphincter. This study aimed to evaluate the results of long-term pneumatic balloon dilatation treatment in our clinic for children diagnosed with achalasia. MATERIALS AND METHODS: Pediatric patients who underwent pneumatic balloon dilatation with a diagnosis of achalasia in our pediatric gastroenterology clinic between 2016 and 2021 were included in the study. Demographic data of the patients, clinical findings at diagnosis, and follow-up results were evaluated retrospectively. RESULTS: Ten patients who underwent 18 pneumatic balloon dilatation operations were included in the study. The mean follow-up period of the patients was 23.7 ± 14.1 months. It was observed that the procedure was performed once in 3 (30%) patients, twice in 2 (20%) patients, and 3 times in 3 (30%) patients. It is noteworthy that the diameter of the balloon used in the first procedure in patients who needed repeated operations was less than 30 mm. No complications were observed except for chest pain, which was detected in 1 patient. CONCLUSION: When the patients who needed recurrent dilatation were evaluated, it was noted that the diameter of the balloon in which the first procedure was performed in these patients was smaller. This study is an important contribution to the literature due to the scarcity of the pediatric achalasia data, in which long-term results related to pneumatic balloon dilatation are reported in Turkey.

Parenthood in pediatric liver transplant patients.

Liver transplantation has become a universally accepted treatment for numerous congenital and acquired hepatic disorders that cause liver failure. Without liver transplantation, patients in their reproductive years are afflicted with oligospermia or azoospermia in men and amenorrhea in women, with infertility being a consequence in both sexes. The aim of this study is to describe our experiences concerning the parenthood of pediatric individuals who are successful recipients of liver transplantations coming into the reproductive years of life. We retrospectively analyzed data of 207 pediatric liver transplanted patients (96 women, 111 men). Among them, three women conceived and delivered four babies, and two men admitted to paternity of two children after they all had been recipients of liver transplants. All female transplant recipients had received tacrolimus-based immunosuppression. Preterm delivery was the most clinically important complication among these patients. Only one of the female patients experienced hypercalcemia during the pregnancy. None had any other complications such as hypertension, preeclampsia, cholestasis, or diabetes. There was no graft insufficiency, rejection, or birth defect. We concluded that maternity and paternity in liver transplant patients show normal outcomes even though this procedure occurs in childhood, and pregnancy did not seem to impair graft function in patients receiving immunosuppressive drugs.

The effects of Mediterranean diet on hepatic steatosis, oxidative stress, and inflammation in adolescents with non-alcoholic fatty liver disease: A randomized controlled trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in children and adolescents. The optimal dietary strategy to improve hepatic stetatosis and reduce oxidative stress and inflammation in adolescents is unknown. OBJECTIVE: This study was conducted to evaluate the effect of Mediterranean diet (MD) versus low-fat diet (LFD) on hepatic steatosis, inflammation, and oxidative stress in adolescents with obesity and NAFLD. METHODS: Adolescents diagnosed with NAFLD between the ages of 11-18 years were randomized to either a MD or conventional LFD (control diet) for 12 weeks. Dietary status, anthropometry, body composition, and biochemical parameters were evaluated. Hepatic steatosis was determined by ultrasonography. RESULTS: A total of 44 participants completed the study. At the end of the study, severity of hepatic steatosis, serum transaminase levels, and insulin resistance decreased significantly in both groups with no significant differences between groups except for aspartate aminotransferase (AST). The amount of decrease in AST levels in the MD group was greater than the LFD group (p < 0.05). In the MD group, serum total antioxidant capacity, paraoxanase-1, and glutathione peroxidase levels increased (p < 0.05); it did not change in the LFD group compared to baseline (p > 0.05). C-Reactive Protein (CRP) levels decreased only in the MD group (p = 0.008), interleukine-6 decreased only in the LFD group (p = 0.031). CONCLUSION: Consumption of MD and LFD for 12 weeks in adolescents with obesity and NAFLD reduced BMI, fat mass, hepatic steatosis, and insulin resistance, improved high transaminase levels, and had positive effects on inflammation and oxidative stress. Registered under ClinicalTrials.gov Identifier no. NCT04845373.

Determination of High-Resolution HLA-DQB1 Suballeles and IL-17 Polymorphisms in Turkish Pediatric Patients.

Celiac disease (CD) is an autoimmune enteropathy in the small intestine caused by gluten intolerance of the patients. The most important genetic disease-related factor is human leukocyte antigen (HLA)-DQ polymorphism. Association between interleukin (IL)-17A expression of CD4 + T cells and various autoimmune diseases has been reported. The aim of this study was to investigate the relationship between single nucleotide polymorphism (rs2275913) IL-17A and HLA-DQ polymorphisms in Turkish pediatric celiac patients. Study group included 125 pediatric celiac patients with CD and 100 healthy pediatric controls. Deoxyribonucleic acid was isolated from peripheral blood samples. IL-17A polymorphism (rs2275913) was analyzed by polymerase chain reaction-restriction fragment polymorphism method. IL-17A polymorphism and low-/high-resolution HLA-DQ results of patients were evaluated. GG and GA genotype frequencies of IL-17A (rs2275913) polymorphism were significantly higher ( p < 0.05) in the CD patients than the control group. HLA-DQB1*02 and HLA-DQA1*05 alleles were detected in patients, while HLA-DQB1*03 and HLA-DQA1*01 alleles in the control group. Also, when we compared the patient and control groups in terms of HLA-DQ-DR haplotypes, HLA-DQB1*02-DQA1*05-DRB1*03 was found with the relative risk of 42.5 ( p < 0.05). As a result of high-resolution HLA-DQB1 typing, DQB1*02:01 and DQB1*03:02 were at high frequency ( p < 0.05; in 25 patient group). IL-17A (rs2275913) polymorphism genotype frequency was found to be significant in the patient group compared with the control group. The most common HLA-DQB1 suballele was observed as DQB1*02:01.

Gilbert Syndrome and Genetic Findings in Children: A Tertiary-Center Experience from Turkey.

OBJECTIVE: Gilbert syndrome (GS) is a disease characterized by mildly elevated indirect serum bilirubin levels due to mutation in the promoter of the UGT1A1 gene, which causes a decrease in uridine diphosphate glucuronyltransferase enzyme activity. Gilbert syndrome should be considered based on clinical and laboratory findings in differential diagnosis, which can be supported by genetic analysis. This study aimed to evaluate the clinical findings and UGT1A1 mutations of children with Gilbert syndrome. MATERIALS AND METHODS: Patients who were admitted to the pediatric gastroenterology clinic and who were considered to have Gilbert syndrome based on clinical and laboratory findings were included in the study. The UGT1A1 analysis was performed by Sanger sequence analysis. RESULTS: A total of 56 children were included in the study. A(TA)7TAA, A(TA)6TAA, and (TA)6/7 allele promoter polymorphism was detected in 75.5%, 22.5%, and 2% of the patients, respectively. Other than these, in 3 patients, 3 different sequence variants associated with GS [c.880_893delinsA (p.Tyr294MetfsTer69) and c.1091C>T(p.Pro365Leu)] were detected. CONCLUSION: We detected 7 TA repeats in the majority of our patients. A mild bilirubin elevation was determined in cases with 6 repetitions that were not considered risky for Gilbert syndrome. We concluded that the c.880_893delinsA (p.Tyr294MetfsTer69) variant, previously shown to be associated with Crigler-Najjar syndrome type I, may also be associated with partial enzyme deficiency leading to the Gilbert syndrome phenotype.

Evaluation of Children Undergoing Endoscopic Procedures During the Normalization of the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Given that procedures involving gastrointestinal tract lumens are high-risk and aerosol forming, the functioning of endos- copy units has been reorganized during the coronavirus disease 2019 pandemic. Guidelines recommend that all personnel should carry out procedures in a negative-pressure room with personal protective equipment; in the absence of a negative-pressure room, an ade- quately ventilated room should be used. During the normalization of the coronavirus disease 2019 pandemic, this study aimed to evalu- ate children who were treated in our endoscopy unit without a negative-pressure chamber in terms of coronavirus disease 2019 after procedures. METHODS: Patients were questioned and evaluated prospectively for symptoms and contact with coronavirus disease 2019 patients on before and 7th and 14th days after the procedure. RESULTS: Seventy-eight procedures were performed on 69 patients over a 3-month period. The mean age of patients was 12.0 ± 5.1 years. Among all the procedures performed, 54 (69.2%) involved upper gastrointestinal system (GIS) endoscopy and 24 (30.8%) involved colo- noscopy. Furthermore, 72 (91.3%) of the procedures were performed in the pediatric endoscopy unit, and 6 (7.7%) were performed in the operating room. No coronavirus disease 2019 symptoms or presence was detected in the patients. CONCLUSION: The ideal setting for an endoscopic procedure is in a negative-pressure chamber. However, this study has shown that endoscopic procedures can be performed in units without negative-pressure rooms but with appropriate protective equipment and evaluation of patients for coronavirus disease 2019 symptoms.

Efficiency of azathioprine monotherapy for maintenance treatment of autoimmune hepatitis in children.

INTRODUCTION: Autoimmune hepatitis (AIH) is a common pediatric liver disease and long-term remission is usually maintained with low dose prednisolone and azathioprine (AZA). The aim of this study is to evaluate the efficiency of AZA monotherapy for maintenance treatment of children with AIH. MATERIALS AND METHODS: This study was a retrospective analysis of the 55 children with AIH. Patients were divided into two groups: combination therapy (CT) and AZA group based on maintenance therapy. Results of these two different maintenance treatments were compared in children with AIH. RESULTS: The mean age of the children was 10.67 ± 4.30 years (61.8% females) with a mean follow-up period of 46.8 ± 33.6 months. For maintenance treatment, 39 (70.9%) patients received AZA and 16 (29.1%) patients received CT. Relapse was observed in nine (19.6%) cases in the follow-up period; two were in the CT group (2/16; 12.5%) and seven (7/39; 17.9%) were in the AZA group (P = 0.620). In AZA group, the duration of remission was 22.2 ± 6.1 months and that was longer than CT group (P = 0.025). CONCLUSION: Our study suggests that AZA monotherapy is an effective and safe therapy for maintaining remission in children with AIH. AZA monotherapy may be used for maintenance treatment of children with AIH, except in cases of overlap syndrome and also to avoid side effects of long-term used steroids and to improve treatment compliance in proper cases.

Evaluation of growth after liver transplantation in Turkish children.

AIMS: Currently, the main interest in childhood liver transplantation (LT) is to prevent long-term complications and optimize growth. The aim of this study is to analyze (1) nutritional status in the pretransplantation period, and (2) posttransplantation growth and associated factors in children. PATIENTS AND METHODS: Eighty children were included in the study. Height (Z (H)) and weight (Z (W)) Z scores were calculated before transplantation and postoperatively at the 6th month and 1st, 2nd, 3rd, 4th, and 5th year. RESULTS: Patients' Z (H) and Z (W) scores at LT were -1.6 ± 1.3 and -1.5 ± 1.4, respectively. Both Z (H) and Z (W) scores increased after LT, especially in the first 6 months, and then continued to rise gradually. Both reached beyond -1 Z score at 2nd year and -0.5 at 4th year. Age, primary diagnosis, total steroid dose (<1,000 mg), and absence of rejection episodes had positive impact on posttransplantation growth, whereas gender, immunosuppression type, surgical complications, and presence of tumor had no impact on posttransplantation growth. Age at time of LT was negatively correlated with Z (W) score at 5th year (P = 0.02, r = -0.43). Both Z (W) and Z (H) scores at time of LT were positively correlated with Z (W) and Z (H) scores and negatively correlated with ∆Z (W) and ∆Z (H) scores at 5th year. CONCLUSIONS: LT is not only a modern, life-saving treatment technique but also an efficient method of facilitating growth, an indispensable component of childhood and the best indicator of health.

Epidemiology of Candidemia in Children over 7 Years in a Medical Center in Turkey.

The aims of the study were to describe Candida species in children with candidemia, to determine the changing epidemiology of candidemia over time in our tertiary care hospital, and to examine the demographic and clinical characteristics of patients with candidemia caused by parapsilosis and nonparapsilosis Candida spp. From 2012 to 2018, we identified a total of 126 cases of candidemia. The most commonly isolated Candida sp. was C. parapsilosis (n = 71, 56.3%), followed by C. albicans (n = 34, 26.9%). A total of 21 candidemia episodes (16.6%) were caused by other Candida species. Patients were divided into two groups (parapsilosis and nonparapsilosis) to identify any potential differences between the groups in terms of risk factors, mortality, and antifungal resistance. The median age of the patients, the median durations of the hospital and pediatric intensive care unit stay, receipt of immunosuppressive therapy within 2 weeks of developing candidemia, the rate of using total parenteral nutrition, need for mechanical ventilation, and receipt of carbapenems were statistically significantly higher in the parapsilosis group than in the nonparapsilosis group (P = 0.020, P = 0.001, P = 0.011, P = 0.036, P = 0.002, P = 0.038, and P = 0.004, respectively). The overall 30-day mortality rates (4.2% versus 3.6%) and resistance to fluconazole (33.8% versus 32.7%) were similar between the groups (P = 0.790 and P = 0.860, respectively). The distribution of Candida strains isolated in this study was consistent with the global trend, with C. parapsilosis being the most commonly identified species. Determining local epidemiologic data at regular intervals in candidemia cases is important in terms of determining both the changing epidemiology and empirical antifungal agents. IMPORTANCE In our study, the changing epidemiology of Candida species in candidemia in children was evaluated. The dominance of Candida parapsilosis species in the changing epidemiology was remarkable. We found that fluconazole resistance was high in both parapsilosis and nonparapsilosis groups. Updating local epidemiologic data at certain intervals in candidemia cases is important in determining both the changing epidemiology and empirical antifungal agents.

Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With Inflammatory Bowel Disease: A Multicenter Study.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). CONCLUSION: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

Infectious complications in pediatric liver transplantation candidates.

We analyzed infections that occurred within one month prior to LT, identified factors associated with their occurrence and effect of infections on post-transplant mortality. The study group included 40 consecutive children who underwent LT. Sites and types of infection and culture results were recorded prospectively. IID was assessed. Risk factors for the infectious events were analyzed. Forty infection episodes were found in 24 patients (60%); 90% were bacterial, 7.5% fungal, and 2.5% viral. Overall, IID was 38.2 per 1000 patient days. Sites of bacterial infection were urinary tract in 13 events (36.1%) and blood stream in 11 events (30.5%). Bacteremia (culture positive infection episodes) was identified in 19 events (52.7%). Gram-negative isolates were twice as frequent as Gram-positive infections (63.1% vs. 36.9%). Risk factors for the infectious complications were young age, low body weight, prior abdominal surgery, chronic liver disease related to biliary problems, presence of ascites, portal hypertension and cirrhosis, and high PELD score (p < 0.05 for all). Infectious complications in pediatric LT candidates are common. Preventive measures are important not only to reduce the infectious complications but also to prevent the post-operative mortality.

A rare cause of refractory ascites in a child: familial Mediterranean fever.

Familial Mediterranean fever (FMF) is hereditary episodic febrile syndrome characterized by acute attacks of fever and serosal inflammation, generally lasting 1-3 days and resolves spontaneously. Apart from abdominal pain, patients may present with variety of abdominal manifestations such as acute peritonitis, mechanical intestinal obstruction, diarrhea, bowel infarction, amyloidosis and small amounts of peritoneal fluid during the acute attacks. A 6-year-old boy was admitted with massive ascites. After extensive laboratory investigations, no causative agent could be identified. On subsequent days, he developed fever and skin eruptions. Acute-phase reactants were increased. A second tomography revealed cystic fluid collection near the anterior side of spleen that invades the stomach. An exploratory was performed and histopathological examination of the all resected specimens revealed mix inflammatory cell infiltrate associated with severe myofibroblast proliferation suggesting chronic inflammatory process on the mesenteric region. A diagnosis of FMF was suspected based on the clinical, laboratory and histopathological findings, and a trial of colchicine therapy initiated. Ascites and other serosal inflammations improved within 1 week without any recurrence during the next 12-month period on colchicine treatment. Atypical presentations of FMF have been increasingly reported. Pediatricians should keep FMF in mind in the differential diagnosis of massive ascites especially in regions where hereditary inflammatory disease are common.

Liver Involvement in Children with Alpha-1 Antitrypsin Deficiency: A Multicenter Study.

PURPOSE: Alpha-1 antitrypsin deficiency (A1ATD) in one of the most common genetic causes of liver disease in children. We aimed to analyze the clinical characteristics and outcomes of patients with A1ATD. METHODS: This study included patients with A1ATD from five pediatric hepatology units. Demographics, clinical findings, genetics, and outcome of the patients were recorded (n=25). RESULTS: Eight patients (32.0%) had homozygous PiZZ genotype while 17 (68.0%) had heterozygous genotype. Patients with PiZZ genotype had lower alpha-1 antitrypsin levels than patients with PiMZ genotype (37.6±7.7 mg/dL vs. 66.5±22.7 mg/dL, p=0.0001). Patients with PiZZ genotype were diagnosed earlier than patients with PiMZ genotype, but this was not significant (13±6.8 months vs. 23.7±30.1 months, p=0.192). Follow-up revealed the death of one patient (12.5%) with a homozygous mutation, and revealed that one patient had child A cirrhosis, five patients (62.5%) had chronic hepatitis, and one patient (12.5%) was asymptomatic. Nine of the 17 patients with a heterozygous mutation had chronic hepatitis (52.9%), two (11.7%) had child A cirrhosis, and six (35.2%) were asymptomatic. Overall, 18 (72%) of the 25 children had liver pathology in the long-term. CONCLUSION: Although prevalence is rare, patients with liver disorders should be checked for alpha-1 antitrypsin levels. Moreover, long-term follow-up is essential because most patients have a liver pathology.

Outcome of Children With Intestinal Failure Due to Waardenburg Syndrome From an Intestinal Transplant Center: A Case Series.

Waardenburg syndrome is a genetic disease characterized by hearing loss and pigmentation abnormalities. Waardenburg syndrome type 4 is very rare, and children with Waardenburg syndrome type 4 present with intestinal aganglionosis. The associated findings and severity of Waardenburg syndrome type 4 may also differ significantly between cases. Intestinal insufficiency is probable and creates difficulties in terms of treatment; intestinal transplant may be required. In this case report, we present 4 cases of patients with Waardenburg syndrome who have intestinal issues, 2 of whom underwent small bowel transplant. Appropriate surgical and nutritional management should be provided for patients with Waardenburg syndrome type 4 who have gastrointestinal manifestations.