Successful Management of l-Asparaginase-Associated Pancreatitis With Octreotide and Pegylated Asparaginase in 2 Patients With Acute Lymphoblastic Leukemia: Is There a Different Rare Warning Sign of Hypoglycemia for l-Asparaginase-Associated Pancreatitis?

l-Asparaginase (l-Asp) is a critical component of chemotherapy for acute lymphoblastic leukemia (ALL). However, toxic effects associated with l-Asp, such as hepatic dysfunction, pancreatitis, hypercholesterolemia, and hyperglycemia, have occurred. In addition, acute pancreatitis is a significant life-threatening adverse event associated with ALL. We describe 2 patients with ALL who had l-Asp-associated pancreatitis (AAP), with one patient presenting with hyperglycemia and the other presenting with hypoglycemia during induction treatment. When octreotide was administered to both of these patients, the clinical findings and laboratory data were improved. AAP was not repeated after treatment with pegylated asparaginase. Although AAP has a high risk of mortality and morbidity in childhood, APP treatment with appropriate agents, such as octreotide, can be successful.

Clinical findings in five Turkish patients with citrin deficiency and identification of a novel mutation on SLC25A13.

Background Citrin deficiency (CD) is an autosomal recessive genetic disorder caused by a defect in the mitochondrial aspartate/glutamate antiporter, citrin. Three clinical manifestations have been described until today. Case presentation We reported 5 CD patients from two families. Four patients were male and one patient was female. Two of them have NICCD (neonatal intrahepatic cholestasis caused by citrin deficiency); three of them have CTLN2 (adult-onset type II citrullinemia). Both NICCD patients showed typical clinical and biochemical changes with a diagnosis confirmed by mutations in the SLC25A13 gene. We detected a previously unreported homozygous novel mutation c.478delC (L160Wfs*36 ) on the SLC25A13 gene. All of the CTLN2 patients were siblings. Proband was a 15-year-old mentally retarded and autistic male who had admitted to our emergency with disorientation. Laboratory data showed hyperammonemia and citrullinemia. Conclusions Two different profiles of age-related CD have been depicted with this article. It has been aimed to underline that the CD can be observed in different forms not only in neonatals or little infants but also in adolescents. This article is the first case series that covers both NICCD and CTLN2 cases together and that has been published in Turkey. Considering the fact that especially the majority of CTLN2 cases have been identified in Asian countries, our article has vital importance in terms of defining phenotypic features of the disease.

Efficacy and safety of long-term thiopurine maintenance treatment for ulcerative colitis in Turkey: A single-center experience.

BACKGROUND/AIMS: Thiopurines are widely used in the treatment of inflammatory bowel disease, but data are limited. Or aim was to determine the outcome of thiopurine application in children diagnosed with ulcerative colitis (UC). MATERIALS AND METHODS: Forty-eight patients with UC, diagnosed at our center between 2005 and 2016 and applied azathiopurine (AZA), were included in the study. Data were collected retrospectively. The diagnosis of UC was based on the conventional clinical, radiological, histological, and endoscopic assessment. All patients with UC at this intercept were analyzed at the 4- and 6-week and 3-month intervals after remission to determine patient characteristics, thiopurine properties, and its efficacy and toxicity. Determination of remission, relapse, and steroid refractoriness/dependency were guided according to the European Crohn's and Colitis Organisation consensus. RESULTS: Azathiopurine was started at the median 1 month (0-12 months), and it was applied thereafter for maintenance (n=43). Response to remission induction was obtained in 40 (93.7%) patients. The median duration of the AZA treatment was 24 months (5-63). In 34 (85%) of the 40 children, it was well tolerated until the last visit. During the follow-up, adverse events occurred in 6 patients. These are leucopenia, neutropenia, vomiting, diarrhea, and skin rush. CONCLUSION: Thiopurine is an appropriate treatment option for remission in patients with UC. For a long-term follow-up, it is very important to identify patients with UC who have clinical remission with side effects and with thiopurine application.

Helicobacter pylori Infection in Children: Nutritional Status and Associations with Serum Leptin, Ghrelin, and IGF-1 Levels.

BACKGROUND: Helicobacter pylori is associated with gastrointestinal diseases such as gastritis, peptic ulcers, malignancy and lymphoma, and extra-gastrointestinal conditions. H. pylori infection is negatively associated with children's growth. Chronic inflammation of the stomach that results in the loss of appetite and, dysregulation of neuroendocrine hormones such as leptin, and ghrelin are the probable reasons of this negative association. The objective of this study is to determine the serum levels of leptin, ghrelin, and IGF-1 in H. pylori-infected children and their relations with growth. MATERIALS AND METHODS: A hundred and sixty-one school children aged between 6 and 14 years were selected randomly from five primary schools representing a cross section of population. Demographic and sociocultural characteristics, and anthropometric measurements were recorded. Serum H. pylori IgG, insulin-like growth factor-1, leptin, and ghrelin levels were measured in all children. The children were grouped according to the nutritional status and Helicobacter pylori seropositivity. Nutritional indices were compared among groups in association with serum leptin, ghrelin, and insulin-like growth factor-1 levels. RESULTS: H. pylori IgG positivity was found in 34.2%, and 14.9% of children were malnourished. H. pylori seropositivity was significantly higher in older ages (10.32 ± 2.26 vs 9.53 ± 2.36 years, p = .036), and body weight and height Z scores were significantly lower in H. pylori-seropositive children (-0.33 ± 1.08 vs 0.04 ± 1.26, p = .044 and 0.13 ± 0.92 vs 0.23 ± 0.91, p = .018 respectively). H. pylori seropositivity was found to be an independent risk factor for shorter body height (p = .01). Serum leptin, ghrelin, and IGF-1 levels were not associated with H. pylori IgG seropositivity (0.35 vs 0.55 ng/mL, p = .3; 3267.4 ± 753.0 vs 2808.3 ± 911.4 pg/mL, p = .06; 470 ± 176 vs 521 ± 179 ng/mL, p = .32, respectively). CONCLUSIONS: Children infected with H. pylori are prone to short stature. This effect seems to be independent of neuroendocrine hormones.

Mannose-binding lectin may affect pregnancy outcome.

Mannose-binding lectin (MBL) is a component of the innate immune system and acts as a complement activator through the lectin pathway. Genetic variations of MBL and low MBL levels cause several infection problems, which may also be related to pregnancy problems. We aimed to investigate the role of MBL gene codon 54 polymorphism and serum MBL levels in pregnancy problems and premature delivery. In this prospective study, MBL gene codon 54 polymorphism and serum MBL levels were studied in 45 mothers who delivered earlier than 35 gestational weeks. The frequency of MBL gene codon 54 variant allele B was much higher (homozygous 4.4% and heterozygous 33.3%) in the study group mothers than the previously reported frequency in the healthy Turkish population (homozygous 2-6%, heterozygous 12-20%). MBL variant allele B frequency was closely related to low MBL levels (<0.1 µg/ml), vaginitis and increased IL-6 levels. The median MBL levels were lower than the critical level of 0.1 µg/ ml in study mothers who had recurrent miscarriage, infertility, preeclampsia, gestational diabetes mellitus, preterm premature rupture of membranes with duration of longer than 72 hours, tocolysis, histological chorioamnionitis, urinary tract infection and vaginitis. MBL gene codon 54 variant allele B is related to low serum MBL levels, increased IL-6 levels, genitourinary infections and may cause pregnancy-related problems such as infertility, recurrent miscarriage and preterm delivery.

Mannose-binding lectin gene polymorphism and chronic hepatitis B infection in children.

BACKGROUND/AIMS: Mannose-binding lectin (MBL) is a member of innate immune system that activates complement system through lectin pathway. MBL deficiency is associated with susceptibility to infectious diseases. In this study, the relation between MBL gene polymorphism and chronic hepatitis B infection in children is evaluated. PATIENTS AND METHODS: The study included 67 children with chronic hepatitis B and 99 healthy controls. The hepatitis B patients were divided into immuntolerant, chronic inactive, and treatment groups according to their laboratory findings. MBL gene codon 52, 54, and 57 polymorphisms were studied with polymerase chain reaction in all patients and controls. The associations of MBL gene polymorphism with clinical, laboratory, and histopathologic findings were evaluated. RESULTS: Homozygous codon 54 polymorphism of MBL was found significantly higher in chronic hepatitis B patients than controls. Rate of the polymorphism was similar in all groups and, responsive and nonresponsive patients in the treatment group. CONCLUSIONS: The hepatitis B patients who are homozygous for codon 54 of MBL are prone to develop chronic infection. Longitudinal studies with larger groups are needed.

The diagnostic value of endoscopic narrow band imaging in helicobacter pylori gastritis in children.

BACKGROUND/AIMS: In this study we aimed to investigate the sensitivity and specificity of Narrow Band Imaging (NBI) in H. pylori gastritis and compare them with those of rapid urease test and urea breath test. MATERIALS AND METHODS: A hundred sixty-five children who admitted to Uludag University Pediatric Gastroenterology Unit between October 2009-March 2011 with upper gastrointestinal symptoms were consecutively enrolled. During the endoscopy procedure gastric corporeal, antral and fundal images were obtained, afterwards the same areas were visualized with narrow band imaging and images were recorded again. RESULTS: The study included 68 (41.2%) boys and 97(58.8%) girls. The mean age of the patients were 11.88±4.55. Tissue culture positivity and/or histopathological staining for H. pylori was determined in 56 (33.9%) patients (Group 1) and the other patients (n:109, 43.6%) didn't have an evidence of H. pylori infection (Group 2). Narrow band images have supported H. pylori infection in 56.4%. The sensitivity of narrow band images for determining H. pylori infection was 92.86% (95% CI 82.7-98), specificity was 62.39% (95% CI 52.6-71.5). CONCLUSION: Our study is the first to show the role of NBI in diagnosing H. pylori infection in children, as well as determining the sensitivity and specificity of the technique. The specificity is low; however, we suggest that the specific mucosal view of H. pylori gastritis provided by NBI is useful for identifying the areas from which the biopsies should be taken. Moreover, by using this technique, treatment of H. pylori infection may be initiated immediately without performing rapid urease test and without waiting for histopathology report and tissue culture.

Prevelance of hepatitis D co-enfection in children with hepatitis B infection: cross-sectional analyses from Western Turkey.

BACKGROUND/AIMS: Effective hepatitis B virus control has warranted a decline in hepatitis B virus prevalence over the world with a relevant reduction in hepatitis B virus-associated delta hepatitis. However, despite the dramatic decline in hepatitis D virus infection rate, no further decrease was recorded after 2000. This cross-sectional study aims to investigate: I- The prevalence of hepatitis D virus co-infection in children with hepatitis B virus infection in Western Turkey; II- The influence of neonatal hepatitis B virus vaccination on hepatitis D virus co-infection rate; and III- The impact of co-infection on prognosis of liver disease. MATERIALS AND METHODS: Serological markers of hepatitis B virus and hepatitis D virus infections were determined by ELISA in patients with chronic hepatitis during immune tolerance, immunoactive, HBeAg-negative chronic, and inactive carrier state. Delta co-infection rate was evaluated in two groups, children born before and after the national neonatal mass vaccination has started (before and after 2000). Viral load, serum alanine aminotransferase, and histological grade were evaluated in co-infected cases. RESULTS: Overall hepatitis delta virus infection rate was 1,76% (3/170); two patients with eAg-negative chronic hepatitis B and one patient in the immunoactive phase were infected with hepatitis D virus. Mean fibrosis score of hepatitis D virus -infected cases and hepatitis B virus -infected counterparts were 4±1,7 and 1,3±1, respectively (p: 0,006). Hepatitis D virus infection was detected in 2 out of 158 children born before and in 1 of 12 born after the neonatal vaccination program. Hepatitis B e-antibody was detected in two patients with delta co-infection (11 and 6 years old), and all mothers of delta hepatitis cases were chronically hepatitis B virus-infected. CONCLUSIONS: Delta hepatitis is rare among hepatitis B virus-infected children in the Western region of Turkey. Despite the success of the national vaccination program, delta hepatitis is not a vanishing disease and it has a grave prognosis due to development of early cirrhosis.

Histological chorioamnionitis: effects on premature delivery and neonatal prognosis.

BACKGROUND: Chorioamnionitis is closely related to premature birth and has negative effects on neonatal morbidity and mortality. METHODS: In this prospective study, 43 mothers who delivered earlier than 35 gestational weeks and their 57 infants were evaluated clinically and with laboratory findings. Placentas and umbilical cords were investigated histopathologically for chorioamnionitis and funisitis. RESULTS: The overall frequency of clinical and histological chorioamnionitis (HCA) was 8.3% and 23.2%, respectively. The frequency of HCA was 47.3% and 83.3% in mothers delivered <32 weeks and <30 weeks, respectively. Maternal demographic and clinical findings and also leukocyte and C-reactive protein values were not indicative of HCA. Infants of mothers with HCA had significantly lower Apgar scores together with higher SNAP-PE-II and CRIB scores. These infants had increased mechanical ventilator and surfactant requirements, higher incidences of patent ductus arteriosus, early sepsis, and bronchopulmonary dysplasia, and higher mortality rates. The effect of HCA on neonatal morbidity and mortality was more prominent than the effect of low birthweight and lower gestational age. CONCLUSION: Chorioamnionitis not only causes premature deliveries, but is also associated with neonatal complications and increased mortality. Clinical findings and infectious markers in mother or infant do not predict the diagnosis of histological chorioamnionitis. Therefore, placental histopathology may have a role in predicting neonatal outcome in premature deliveries, especially those below 30 weeks.

Pediatric Gaucher experience in South Marmara region of Turkey.

BACKGROUND/AIMS: The aim was to represent the clinical characteristics of six children with Gaucher disease and to describe the results of three years' enzyme replacement therapy. MATERIAL AND METHODS: The data of six Gaucher patients treated with imiglucerase for more than three years were collected. Age, gender, anthropometric measurements, physical examination findings, ophthalmological evaluations, blood counts, liver function tests, liver and spleen sizes, and bone mineral density of the patients were recorded. Clinical presentations, progressions and therapeutic achievements were evaluated. RESULTS: At the time of diagnosis, all patients were clinically type 1 Gaucher disease. Bone lesions, thrombocytopenia and hepatosplenomegaly were found in all patients at diagnosis. After three years of therapy, normalization of blood cell counts, liver and spleen sizes, bone mineral density, and growth was achieved in all patients. Two patients developed neurological symptoms on enzyme replacement therapy, and the diagnosis in these patients was changed to Gaucher type 3. We observed progression of vertebral bone lesions in three patients despite treatment. CONCLUSIONS: The results of enzyme replacement therapy are satisfying, but the possibility of deterioration in clinical findings despite therapy should be kept in mind.

Mannose-binding lectin gene polymorphism and early neonatal outcome in preterm infants.

BACKGROUND: Mannose-binding lectin (MBL) as a component of innate immunity plays an important role in preterm infants in whom adaptive immunity is not sufficiently developed. Polymorphisms in immunoregulatory genes influence the response to infection and subsequent inflammation. Infection and inflammation have been implicated in the mechanisms responsible for many of the diseases in the preterm newborns. OBJECTIVES: The aim of the study was to investigate the relationship between MBL gene polymorphism and early neonatal outcome in preterm infants. METHODS: Codon 54 and 57 polymorphisms in MBL2 gene were genotyped in 99 preterm infants admitted to the Neonatal Intensive Care Unit at Ege University Children's Hospital. RESULTS: Overall frequencies of sepsis and early-onset sepsis were higher in the group of infants with MBL polymorphism when compared to infants with wild-type MBL genotype (p = 0.008, 0.009, respectively). Maximum Tollner sepsis score in the first 3 days of life was higher for the infants with variant MBL genotype (p = 0.0278). More infants in the variant MBL group had significant patent ductus arteriosus when compared to infants with wild-type MBL (27.8 vs. 9.5% respectively, p = 0.037). CONCLUSION: MBL gene polymorphism was associated with increased frequency of clinical sepsis particularly with early neonatal sepsis and also with higher Tollner sepsis scores and increased frequency of patent ductus arteriosus in infants. Overall mortality and incidence of culture proven sepsis, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia and necrotizing enterocolitis were not found to be related to MBL genotype.

Do liver IL-12 levels predict sustained response to IFN-alpha therapy in children with chronic hepatitis B?

The aim of this study is to investigate the immunoregulatory role of interleukin-12 and interferon-gamma in children with chronic hepatitis B who are treated with interferon-alpha therapy. The patients were divided into 2 groups: Group I included 16 children with naive chronic replicative hepatitis B infection, and Group II included 6 children who are inactive hepatitis B virus (HBV) carriers. Group I received interferon-alpha subcutaneously (10 mU/m(2)/dose), 3 times a week during 4 months. Initial serum alanine aminotransferase (ALT) levels, hepatitis B serologic markers, serum interleukin-12 and interferon-gamma levels were measured. In Group I, laboratory tests were re-evaluated in the second and fourth months. Liver biopsy was performed in all patients and samples were used for tissue interleukin-12 level evaluation and histopathological examination. Hepatic activity index (HAI) and serum interferon-gamma were significantly higher in Group I (P < 0.05). Initial tissue interleukin-12 levels in Group I were low but a significant increase was observed at the fourth month (P < 0.05). While responder patients in Group I had marked elevation of tissue interleukin-12 levels, nonresponders did not reveal considerable changes at the fourth month evaluation. A negative correlation was found between serum HBV-DNA copies and interferon-gamma levels prior to therapy (P < 0.01, r: -0.66). The analysis of cytokine levels with serum transaminases demonstrated a positive correlation between the tissue interleukin-12 levels at the fourth month and serum ALT levels at the beginning and second month of the therapy (r: 0.77, P < 0.05 and r: 0.92, P < 0.05, respectively). This is the first study emphasizing the relationship between tissue cytokine levels and therapy success. Understanding the course of chronic hepatits B in the pediatric population will help us to clarify some debates on the treatment.

Molecular investigations to improve diagnostic accuracy in patients with ARC syndrome.

Arthrogryposis, Renal dysfunction and Cholestasis (ARC) syndrome is a multi-system autosomal recessive disorder caused by germline mutations in VPS33B. The detection of germline VPS33B mutations removes the need for diagnostic organ biopsies (these carry a>50% risk of life-threatening haemorrhage due to platelet dysfunction); however, VPS33B mutations are not detectable in approximately 25% of patients. In order further to define the molecular basis of ARC we performed mutation analysis and mRNA and protein studies in patients with a clinical diagnosis of ARC. Here we report novel mutations in VPS33B in patients from Eastern Europe and South East Asia. One of the mutations was present in 7 unrelated Korean patients. Reduced expression of VPS33B and cellular phenotype was detected in fibroblasts from patients clinically diagnosed with ARC with and without known VPS33B mutations. One mutation-negative patient was found to have normal mRNA and protein levels. This patient's clinical condition improved and he is alive at the age of 2.5 years. Thus we show that all patients with a classical clinical course of ARC had decreased expression of VPS33B whereas normal VPS33B expression was associated with good prognosis despite initial diagnosis of ARC.