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IntroductionThe coexistence of progressive familial intrahepatic cholestasis type 2, failure to thrive due to an LPIN3 mutation, and stigmata of neonatal neurofibromatosis represents a complex diagnostic challenge. Case report: We present a child with cholestasis requiring hepatic transplantation, explained by the progressive familial intrahepatic cholestasis type 2, failure to thrive could be contributed to by the LPIN3 mutation, and skin findings along with the family history of the patient was due to neurofibromatosis type 1. Conclusion: Our case illustrates the complexities of multiple genetic mutations in a child.
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Colestase Intra-Hepática , Colestase , Neurofibromatose 1 , Criança , Colestase Intra-Hepática/genética , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genéticaRESUMO
INTRODUCTION: Hepatitis-associated aplastic anemia is a rare type of acquired aplastic anemia that occurs after hepatitis. This study investigated cases with hepatitis-associated aplastic anemia. METHODS: The files of patients with hepatitis-associated aplastic anemia who were followed up in our hospital between 2011-2019 were reviewed retrospectively. RESULTS: A total of 15 patients with hepatitis-associated aplastic anemia (10 males, 5 girls; mean age 10.26 ± 3.61 years) were analyzed. The mean duration between hepatitis and aplastic anemia was 5.06 ± 4.19 months. The majority of patients had mild hepatitis. The causes of hepatitis were detected only in six patients: three had hepatitis B, one had hepatitis A, one had autoimmune hepatitis and, one had a hydatid cyst. The cause of hepatitis was not found in nine patients. Only one patient with hepatitis-associated aplastic anemia developed spontaneous remission, and the others required immunosuppressive therapy and/or hematopoietic stem cell transplantation. Only one patient died because of sepsis. The other patients are still under follow-up and treatment. CONCLUSION: Patients with hepatitis-associated aplastic anemia, mostly of unknown cause, can be successfully treated with immunosuppressive therapy and/or hematopoietic stem cell transplantation.
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Anemia Aplástica/etiologia , Hepatite/complicações , Adolescente , Anemia Aplástica/patologia , Criança , Feminino , Humanos , MasculinoRESUMO
AIM: The practical value of using fibre-enriched enteral feeding regimens to rehabilitate malnourished children remains inconclusive. This study determined the usage patterns, gastrointestinal tolerance, anthropometrics and safety of high-fibre enteral feeding in malnourished children with growth failure. METHODS: This Turkish observational study between February 2013 and June 2015 comprised 345 paediatric patients from 17 centres with malnutrition-related growth failure, with a weight and height of <2 SD percentiles for their age. Changes in anthropometrics, gastrointestinal symptoms, defecation habits and safety data relating to adverse events were analysed during the six-month follow-up period. RESULTS: Most subjects (99.7%) were supplemented with enteral feeding. The absolute difference and 95% confidence interval values for the Z scores of height for age, weight for age, weight for height and body mass index for height increased significantly in four months to six months to 0.21 (0.09-0.32), 0.61 (0.51-0.70), 0.81 (0.56-1.06) and 0.70 (0.53-0.86), respectively (p < 0.001 for each). The percentage of patients with normal defecation frequency significantly increased from 70.3% to 92.8% at the four months to six months visit (p = 0.004). Adverse events occurred in 15 (4.3%) of patients. CONCLUSION: Using a six-month high-fibre enteral feeding was associated with favourable outcomes in anthropometrics, appetite, gastrointestinal tolerance and safety in malnourished children.
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Transtornos da Nutrição Infantil/terapia , Fibras na Dieta , Nutrição Enteral , Transtornos da Nutrição do Lactente/terapia , Antropometria , Criança , Pré-Escolar , Defecação , Feminino , Gastroenteropatias/epidemiologia , Humanos , Lactente , Masculino , Turquia/epidemiologiaRESUMO
Background Wilson's disease (WD) is a copper metabolism disorder that causes hepatolenticular degeneration. It is important to diagnose WD before central nervous system involvement. Purpose To demonstrate the early susceptibility changes associated with the copper accumulation in the brain of neurologically asymptomatic pediatric patients with WD using quantitative susceptibility mapping (QSM). Material and Methods Twelve patients with neurologically asymptomatic WD (mean age = 13.7 ± 3.3 years) and 14 age-matched controls were prospectively examined using a 1.5-T clinical scanner. Routine magnetic resonance (MR) sequences and a three-dimensional multi-echo spoiled gradient echo (GRE) sequence were used and QSM maps were reproduced. The quantitative susceptibility of corpus striatum, thalamus, substantia nigra, and pons were analyzed with the region of interest analysis on QSM maps. The susceptibility values of two groups were statistically compared using a two-sample t-test. Results Conventional MR images of the patients and control group were similar. However increased magnetic susceptibility in the thalamus, pons and left posterior putamen were observed in the patients compared to the control group ( p < 0.05). Conclusion We observed statistically increased susceptibility values in the brains of neurologically asymptomatic patients with WD although the conventional MR images were normal. This might be compatible with early brain impairment, before neurological symptoms occur.
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Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Degeneração Hepatolenticular/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Criança , Estudos de Avaliação como Assunto , Feminino , Degeneração Hepatolenticular/diagnóstico por imagem , Humanos , Imageamento Tridimensional/métodos , Masculino , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: To determine presence and distribution of enamel defects, recurrent oral aphthous lesions (RAS) and dental caries in children with Celiac Disease (CD) and compare the results with a healthy control group. METHODS: Twenty- five CD patients age between 4- 16 years with no other systemic disease, were examined in Pediatric Gastroenterology Clinic of Erciyes University, Faculty of Medicine (Kayseri, Turkey) and then referred to Department of Pediatric Dentistry, Faculty of Dentistry for dental examination and treatment. The control group (25 patients) consisted healthy patients referred to the Department of Pediatric Dentistry, Faculty of Dentistry, Erciyes University for restorative treatment. Both the CD group and control group was examined by the same investigator for the following; (1) enamel defects, (2) recurrent aphthous stomatitis, (3) dental caries. RESULTS: The mean dmft values for the CD group and control group were 3.25±3.25 and 4.56±2.87 respectively. The difference was not statistically significant.(P>0.05). The mean DMFT values for the CD and the control group were 3.75±2.62 and 1.83±1.7, respectively. There was a significant difference between the two groups (P<0.01). The prevalence of enamel defects and recurrent apthous stomatitis (RAS) was greater in celiac patients than in the control group. Enamel defects (in at least one permanent tooth) were observed in 12 out of 25 (48%) children in the CD group and four out of 25 children (16%).(P =0.01). Recurrent apthous stomatitis was found in 11/25 (44%) CD group, while no RAS was detected in the control group. CONCLUSION: Celiac Disease (CD) has adverse effects on oral health in term of enamel defect, recurrent aphthous stomatitis and caries score. Pediatricians and dentists especially pediatric dentists should be knowledgeable about oral symptoms of CD. Increased awareness can provide an early diagnosis and prevent long- term complications of this disease. On the other hand, further comprehensive investigations of CD patients can add to our understanding of the efficacy of CD on oral health in children.
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The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naïve (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2-18 (n = 4) and non-GVHD patients between ages 2-50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naïve phenotype (CD62L+ CD44-). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in pro-inflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.
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Linfócitos T CD8-Positivos , Doença Enxerto-Hospedeiro , Lactonas , Sesquiterpenos de Eudesmano , Humanos , Camundongos , Feminino , Animais , Camundongos Endogâmicos C57BL , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante Homólogo , Transplante de Medula ÓsseaRESUMO
Ataxia-telangiectasia (A-T) is an autosomal recessive primary immunodeficiency disease characterized by progressive cerebellar ataxia, telangiectasia, sinopulmoner recurrent infections, and cancer susceptibility. Individuals with A-T are known to be at increased risk of certain malignancies including leukemia, lymphoma, and breast and gastric cancer. We present an 18-year-old case of A-T with Hashimoto thyroiditis who admitted with complaints of nausea, vomiting, anorexia, and weight loss. An upper endoscopic biopsy revealed gastric signet ring cell carcinoma. To the best of our knowledge, we report the first case of signet ring cell carcinoma in the patient with A-T. Our experience with occurrence of Hashimoto thyroiditis and gastric signet ring cell carcinoma in the same case of A-T underlines that the clinicians handling A-T must be vigilant about both malignancy and autoimmune disorders.
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Ataxia Telangiectasia/complicações , Carcinoma de Células em Anel de Sinete/complicações , Neoplasias Gástricas/complicações , Adolescente , Carcinoma de Células em Anel de Sinete/patologia , Evolução Fatal , Feminino , Doença de Hashimoto/complicações , Humanos , Neoplasias Gástricas/patologiaRESUMO
Deficiency of vitamin K predisposes to early, classic or late hemorrhagic disease of the newborn (HDN); of which late HDN may be associated with serious and life-threatening intracranial hemorrhage. Late HDN is characterized intracranial bleeding in infants aged 1 week to 6 months due to severe vitamin K deficiency. Late HDN is still an important cause of mortality and morbidity in developing countries where vitamin K prophylaxis is not routinely practiced. Children with cholestatic liver disease are at risk for developing secondary vitamin K deficiency because of fat malabsorbtion and inadequate dietary intake. In this study, we described 11 infants with cholestatic liver disease with different etiologies exhibiting intracranial hemorrhage (ICH). Six patients underwent surgical evacuation of ICH, following the administration of vitamin K and/or fresh frozen plasma. The possibility of cholestatic liver disease should be considered in the treatment of ICH due to vitamin K deficiency.
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Colestase Intra-Hepática/complicações , Sangramento por Deficiência de Vitamina K/etiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Colestase Intra-Hepática/patologia , Evolução Fatal , Feminino , Células Gigantes , Hepatite/complicações , Hepatite/patologia , Humanos , Lactente , Recém-Nascido , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/patologia , Hemorragias Intracranianas/cirurgia , Imageamento por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos , Plasma , Tomografia Computadorizada por Raios X , Vitamina K/uso terapêutico , Sangramento por Deficiência de Vitamina K/fisiopatologia , Vitaminas/uso terapêuticoRESUMO
OBJECTIVE: Rheumatic diseases in children are chronic and multisystemic diseases. In this study, it was aimed to evaluate gastrointestinal endoscopic findings in children diagnosed as autoimmune or autoinflammatory rheumatic diseases consulted with pediatric gastroenterology for gastrointestinal complaints. METHODS: The patients followed up by the Pediatric Rheumatology Department and consulted to the Pediatric Gastroenterology Department due to gastrointestinal complaints were included in the study. File records of the patients were analyzed retrospectively. RESULTS: A total of 28 patients were included in the study. Twelve of the patients had autoimmune disease (Juvenile idiopathic arthritis [JIA], systemic lupus erythematosus, Sjögren's syndrome, and scleroderma) and the other 16 had autoinflammatory disease (familial Mediterrnean fever, hyper Immunoglobulin D syndrome, undifferantiated systemic autoinflammatory disease, and systemic JIA). Four of the patients with familial Mediterrnean fever also diagnosed as JIA. The mean age of the patients was 11.7±3.5 years. The main gastrointestinal complaints of patients with both autoimmune and autoinflammatory diseases were abdominal pain and diarrhea. Inflammatory bowel disease was found in 33% of those with autoimmune disease and 56% of those with autoinflammatory disease in patients underwent endoscopic evaluation. M694V mutation was present in 62% of the patients with autoinflammatory disease presented with gastrointestinal complaints. CONCLUSION: Both autoimmune and autoinflammatory rheumatic diseases can cause gastrointestinal complaints and should be referred to a pediatric gastroenterologist for early diagnosis.
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Introduction: Elevated transaminases and/or creatine phosphokinase can indicate underlying muscle disease. Therefore, this study aims to determine the frequency of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in male children and Pompe disease (PD) in male and female children with isolated hypertransaminasemia. Methods: This multi-center, prospective study enrolled patients aged 3-216 months with serum alanine transaminase (ALT) and/or aspartate transaminase (AST) levels >2× the upper limit of normal (ULN) for ≥3 months. Patients with a known history of liver or muscle disease or physical examination findings suggestive of liver disease were excluded. Patients were screened for creatinine phosphokinase (CPK) levels, and molecular genetic tests for DMD/BMD in male patients and enzyme analysis for PD in male and female patients with elevated CPK levels were performed. Genetic analyses confirmed PD. Demographic, clinical, and laboratory characteristics of the patients were analyzed. Results: Overall, 589 patients [66.8% male, mean age of 63.4 months (standard deviation: 60.5)] were included. In total, 251 patients (188 male and 63 female) had CPK levels above the ULN. Of the patients assessed, 47% (85/182) of male patients were diagnosed with DMD/BMD and 1% (3/228) of male and female patients were diagnosed with PD. The median ALT, AST, and CPK levels were statistically significantly higher, and the questioned neurological symptoms and previously unnoticed examination findings were more common in DMD/BMD patients than those without DMD/BMD or PD (p < 0.001). Discussion: Questioning neurological symptoms, conducting a complete physical examination, and testing for CPK levels in patients with isolated hypertransaminasemia will prevent costly and time-consuming investigations for liver diseases and will lead to the diagnosis of occult neuromuscular diseases. Trial Registration: Clinicaltrials.gov NCT04120168.
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Background: Human leukocyte antigen (HLA)-G, a member of the HLA family, is crucial for fetomaternal tolerance. Transmembrane or circulating/soluble HLA-G (sHLA-G) is elevated in autoimmune conditions and the tumor microenvironment. Circulating sHLA-G levels and their association with disease activity have not yet been assessed in pediatric patients with inflammatory bowel disease (IBD). This study aimed to quantify the serum sHLA-G levels of pediatric patients with IBD and assess the association of serum sHLA-G with disease activity. Methods: : We enrolled 24 pediatric IBD patients Crohn's disease (CD) and ulcerative colitis (UC), n = 12 each] and 24 healthy controls. Based on the disease activity index, five and seven of the CD patients had mild and moderate/severe disease, respectively, whereas six of the UC patients were in remission and six had mild disease. Serum was collected and sHLA-G levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: : Pediatric patients with CD had significantly higher sHLA-G levels compared with patients with UC and healthy controls. Notably, serum sHLA-G levels were significantly higher in patients with moderate/severe CD than in those with mild CD. Conclusions: : Serum sHLA-G levels correlate with disease activity in pediatric patients with CD and are higher in CD patients than in UC patients. Thus, sHLA-G is a potential biomarker for disease activity in CD.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Criança , Doença de Crohn/patologia , Antígenos HLA-G , HumanosRESUMO
OBJECTIVES: To investigate the rate of laryngospasm with sedation during the esophagogastroduodenoscopy (EGD) procedure in children exposed to passive smoking and to examine the frequency of complications due to laryngospasm. METHODS: A single-blind, prospective, observational study with a total of 518 patients evaluated according to the American Society of Anesthesiologists (ASA) physical status as classification I-II, aged between 1-18 years, and planned to undergo an EGD procedure, were included. Age, gender, weight, ASA assessment, exposure to smoking (the mother, the father, both parents were smokers, or not exposed to smoking), drug doses used in sedation, and anesthesia-related complications, such as cough, decrease in oxygen saturation, and laryngospasm were recorded. RESULTS: Of the 518 patients included in the study, 213 had no smoking exposure history. Oxygen saturation did not decrease below 90% in patients who did not have any smoking exposure. In addition, no laryngospasm was observed in this group. However, 4 (11.4%) of 31 patients whose mother only smoked, 10 (5.1%) of 187 child patients whose father only smoked, and 12 (16.4%) of 61 patients whose mother and father both smoked experienced laryngospasm during the procedure. CONCLUSION: The rate of cough, laryngospasm, and hypoxia development increased during the sedation carried out in the EGD procedure in children who were exposed to passive smoke.Clinicaltrial.gov ID: NCT03920046.
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Laringismo , Poluição por Fumaça de Tabaco , Adolescente , Criança , Pré-Escolar , Endoscopia do Sistema Digestório , Humanos , Lactente , Laringismo/induzido quimicamente , Estudos Prospectivos , Método Simples-Cego , Poluição por Fumaça de Tabaco/efeitos adversosRESUMO
BACKGROUND: The aim of this study was to investigate the frequency of anemia and hepatotoxicity associated with aspirin use in patients with acute rheumatic fever. METHODS: Patients with acute rheumatic fever followed at Erciyes University, Faculty of Medicine, Department of Pediatric Cardiology between 2015-2018 were reviewed retrospectively. RESULTS: A total of 286 patients with acute rheumatic fever were analysed. Aspirin treatment was started in 53 of the 286 patients (18.5%) due to arthritis. The mean age of the patients who used aspirin was 10.7 ± 2.5 years. Aspirin-induced hepatotoxicity developed in 9 (17%) of the 53 patients. Naproxen or ibuprofen was given to these patients as an alternative to aspirin. No side effects occurred in patients receiving naproxen or ibuprofen. In addition, 30% of 53 patients were initially anemic. The mean duration of aspirin use in the hepatotoxic patients who had anemia was longer than patients without anemia (p=0.02). CONCLUSIONS: Patients with acute rheumatic fever should be closely monitored for aspirin hepatotoxicity. When aspirin hepatotoxicity develops, naproxen or ibuprofen treatment can be used safely.
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Anemia , Doença Hepática Induzida por Substâncias e Drogas , Febre Reumática , Adolescente , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Criança , Humanos , Estudos Retrospectivos , Febre Reumática/complicações , Febre Reumática/tratamento farmacológico , Febre Reumática/epidemiologiaRESUMO
OBJECTIVE: The essential characteristics of posterior reversible encephalopathy syndrome (PRES) are the presence of acute onset neurologic symptoms, focal vasogenic edema at neuroimaging, and reversible clinical and/or radiologic findings. This study aimed to evaluate the clinical findings, causes, radiologic findings, and prognoses of patients with PRES. METHODS: Patients with PRES confirmed with clinical and radiologic findings by a pediatric neurologist were evaluated retrospectively. RESULTS: Seventeen patients with PRES were evaluated (mean age at onset, 10.23 ± 4.65 years; range, 2-17 years; girls, 29.4% [n = 5]). The mean length of follow-up was 6 ± 2.3 years (range, 3.4-10 years). Mortality due to primary disease occurred in 4 patients (23.5%) during follow-up. PRES was derived from renal diseases in 10 patients (58.8%), hematologic diseases in 6 patients (35.3%), and liver disease in one patient (5.9%). Hypertension was present in 16 patients (94.1%) at onset of PRES (>99th percentile). Seizure, the most frequent initial symptom, was observed in 82.4% (n = 14). Blurred vision and headache were the initial symptoms in 3 patients (17.6%). Sequelae were observed at magnetic resonance imaging (MRI) in 6 patients. Development of epilepsy was determined as a sequela in 4 patients (23.5%) and mental motor retardation in 2 patients (11.8%). CONCLUSION: Epilepsy is uncommon in patients who have recovered from PRES. The presence of gliosis on MRI and interictal epileptic discharges on electroencephalograms are major risk factors for the development of epilepsy. Antiepileptic treatment can be stopped in the early period in patients with normal MRI and electroencephalogram by eliminating the factors that trigger the seizures.
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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.
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Febre Familiar do Mediterrâneo , Doenças Inflamatórias Intestinais , Mutação , Adolescente , Criança , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/genética , Doença de Crohn/epidemiologia , Doença de Crohn/genética , Febre Familiar do Mediterrâneo/genética , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genéticaRESUMO
Altay D, Özcan A, Ünal E, Deniz K, Özkan KU, Patiroglu T, Arslan D. A rare cause of vomiting in an adolescent: gastric Burkitt`s lymphoma. Turk J Pediatr 2019; 61: 431-435. Burkitt`s lymphoma, which is the most commonly diagnosed pediatric gastrointestinal tumor, usually affects the intestinal tract. However, the diagnosis of gastric Burkitt`s lymphoma in childhood is extremely rare. Here, we have reported the case of an adolescent male patient with vomiting and weight loss symptoms who was diagnosed with Burkitt`s lymphoma of the pyloric antrum. The patient responded very well to chemotherapy and he did not develop tumor lysis syndrome. Based on this case report, gastric Burkitt`s lymphoma might be included in the differential diagnoses of pediatric patients who experience vomiting that results in significant weight loss.
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Linfoma não Hodgkin/complicações , Neoplasias Gástricas/complicações , Vômito/etiologia , Adolescente , Biópsia , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Humanos , Linfoma não Hodgkin/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons , Doenças Raras , Neoplasias Gástricas/diagnóstico , Ultrassonografia , Vômito/diagnósticoRESUMO
BACKGROUND: Children with very early onset inflammatory bowel diseases (VEO-IBD) often have a refractory and severe disease course. A significant number of described VEO-IBD-causing monogenic disorders can be attributed to defects in immune-related genes. The diagnosis of the underlying primary immunodeficiency (PID) often has critical implications for the treatment of patients with IBD-like phenotypes. METHODS: To identify the molecular etiology in 5 patients from 3 unrelated kindred with IBD-like symptoms, we conducted whole exome sequencing. Immune workup confirmed an underlying PID. RESULTS: Whole exome sequencing revealed 3 novel CARMIL2 loss-of-function mutations in our patients. Immunophenotyping of peripheral blood mononuclear cells showed reduction of regulatory and effector memory T cells and impaired B cell class switching. The T cell proliferation and activation assays confirmed defective responses to CD28 costimulation, consistent with CARMIL2 deficiency. CONCLUSION: Our study highlights that human CARMIL2 deficiency can manifest with IBD-like symptoms. This example illustrates that early diagnosis of underlying PID is crucial for the treatment and prognosis of children with VEO-IBD.
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Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Proteínas dos Microfilamentos/deficiência , Idade de Início , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Linfócitos/imunologia , Masculino , Mutação , Fenótipo , Sequenciamento do ExomaRESUMO
OBJECTIVES: Wilson's disease (WD) is characterized with the accumulation of copper in the liver and brain. The objective of this study is to quantitatively measure the susceptibility changes of basal ganglia and brain stem of pediatric patients with neurological WD using quantitative susceptibility mapping (QSM) in comparison to healthy controls. METHODS: Eleven patients with neurological WD (mean age 15 ± 3.3 years, range 10-22 years) and 14 agematched controls were prospectively recruited. Both groups were scanned on a 1.5 Tesla clinical scanner. In addition to T1- and T2-weighted MR images, a 3D multi-echo spoiled gradient echo (GRE) sequence was acquired and QSM images were derived offline. The quantitative measurement of susceptibility of corpus striatum, thalamus of each hemisphere, midbrain, and pons were assessed with the region of interest analysis on the QSM images. The susceptibility values for the patient and control groups were compared using twosample t-test. RESULTS: One patient with WD had T1 shortening in the bilateral globus pallidus. Another one had hyperintensity in the bilateral putamen, caudate nuclei, and substantia nigra on T2-weighted images. The rest of the patients with WD and all subjects of the control group had no signal abnormalities on conventional MR images. The susceptibility measures of right side of globus pallidus, putamen, thalamus, midbrain, and entire pons were significantly different in patients compared to controls (P < 0.05). CONCLUSION: QSM method exhibits increased susceptibility differences of basal ganglia and brain stem in patients with WD that have neurologic impairment even if no signal alteration is detected on T1- and T2-weighted MR images.
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Gânglios da Base/diagnóstico por imagem , Mapeamento Encefálico/métodos , Tronco Encefálico/diagnóstico por imagem , Cobre/análise , Degeneração Hepatolenticular/diagnóstico por imagem , Degeneração Hepatolenticular/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Gânglios da Base/patologia , Tronco Encefálico/patologia , Criança , Feminino , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: To investigate the status of oxidative stress in children with Helicobacter pylori (HP) infection and their relationship with inflammatory parameters. METHODS: At the Pediatric Gastroenterology Department of Erciyes University, Kayseri, Turkey, between January 2004 to August 2005, 39 children undergoing upper gastrointestinal endoscopy were investigated for malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity in gastric tissue and erythrocytes, and presence of HP infection by means of histology. RESULTS: There is an increase of the oxidative stress parameter, MDA, in gastric tissue, but not in erythrocytes in HP (+) patients. The antioxidant enzyme, SOD, levels both in gastric tissue and erythrocytes were not different between HP (+) and HP (-) patients. In 8 HP infected children after treatment with an anti-HP regimen, no change was observed except for tissue SOD activity, which is increased after therapy. No correlation was observed between histological findings and tissue, and erythrocyte MDA levels and SOD activities. CONCLUSION: Oxidative stress has some role in tissue damage in HP infection in children.