Hülya Demir

Background/Objectives: This study examined urinary cholanoid profiles in a descriptive case series evaluated for suspected inborn errors of bile acid synthesis (IEBAS) or unexplained cholestasis. Methods: Urinary excretion of 66 bile acid metabolites was measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS), and concentrations were interpreted as semi-quantitative estimates. In addition, cholesterol, cholestanol, and 7-dehydrocholesterol were analyzed by gas chromatography–mass spectrometry (GC-MS). Results: Five patients had genetically confirmed IEBAS: 3β-hydroxy-Δ5-C27-steroid dehydrogenase (HSD3B7) deficiency in 2 patients and cerebrotendinous xanthomatosis (CTX) in 3 patients. Two patients were subsequently diagnosed with biliary atresia and progressive familial intrahepatic cholestasis type 1. Other patients remained without a definitive etiological diagnosis. Of the two patients with genetically confirmed HSD3B7 deficiency, patient 1 showed a predominance of 3β-hydroxy-Δ⁵ bile acids (63.9% of total urinary bile acids), including sulfated dihydroxy-, glycine-conjugated dihydroxy-, and trihydroxy-Δ⁵ species. Patient 2 had an atypical urinary bile acid profile, with the 3β-hydroxy-Δ⁵ fraction dominated by a monohydroxy species. CTX patients had profiles with a different bile acid group composition; hydroxylated bile acids were reported in 2 patients, whereas no numerical result was reported for 1 patient. The 3β-hydroxy-Δ⁵ bile acid levels in 1 CTX patient were within the observed control range. Two patients also had differential profiles for hydroxylated and 3β-hydroxy-Δ⁵ bile acids, which provided biochemical findings for further etiological evaluation. The species assigned to glycoursodeoxycholic acid predominated in the urinary profiles of the five patients receiving ursodeoxycholic acid. Conclusions: Urinary cholanoid profiling may provide complementary biochemical information alongside the available clinical and genetic findings in the evaluation of suspected IEBAS.

Background/Objectives: This study aims to identify genetic variants associated with early-onset inflammatory bowel disease (IBD) and to improve diagnostic and therapeutic approaches. In selected monogenic IBD cases, treatment included colchicine, interleukin-1 inhibitors, and hematopoietic stem cell transplantation. Methods: This study included patients with early-onset IBD, defined as IBD diagnosed before the age of 10, who were under follow-up at the Department of Pediatric Gastroenterology, Hacettepe University, and agreed to participate between December 2018 and April 2021. Whole-exome sequencing (WES) was performed prospectively in patients without a prior diagnosis of monogenic disease, while clinical and laboratory data were reviewed retrospectively. Identified variants were evaluated for pathogenicity using standard bioinformatics tools. Results: A total of 47 patients were enrolled, including 33 boys (70.2%) and 14 girls (29.8%). The median age at symptom onset was 36 months (IQR: 10–72), and the median age at diagnosis was 3.7 years (IQR: 1.5–7.6). Crohn’s disease was diagnosed in 53.2% (n = 25), ulcerative colitis in 38.3% (n = 18), and unclassified IBD in 8.5% (n = 4). Monogenic IBD was identified in 36.2% (n = 17) of patients, including nine with Familial Mediterranean Fever and others with glycogen storage disease type 1b (n = 2), XIAP deficiency, chronic granulomatous disease, DOCK8 deficiency, IL10 receptor alpha defect, LRBA deficiency, and NFKB2 deficiency (n = 1 each). A novel SLC29A3 gene variant (c.480_481delTGinsCA, p.V161I) (transcript ID: ENST00000479577.2) was identified in 76.6% (n = 36) of patients. Conclusions: This study underscores the importance of genetic variants in early-onset IBD, particularly MEFV and the novel NFKB2. The frequent detection of the SLC29A3 variant may suggest its potential involvement in the pathogenesis of the disease.

Alpha-fetoprotein (AFP) is used as a tumor marker for hepatocellular carcinoma, hepatoblastoma and germ cell tumors. It may also be elevated in infants with some hepatobiliary disorders. The mechanism of AFP elevation in neonatal cholestasis is not known. We retrospectively evaluated serum AFP levels in 53 infants with neonatal cholestasis. Thirty patients (56.6%) had elevated AFP, and the ratio of patients with elevated AFP was significantly high in both the metabolic diseases and idiopathic neonatal hepatitis groups (p=0.021). Serum aspartate aminotransferase (AST) levels increased significantly in patients with elevated AFP (p=0.004). Steatosis was the distinctive histopathological finding of the patients with high AFP. The patients with steatosis had significantly higher standard deviation (SD) score of AFP than the patients without steatosis (p=0.001). We have shown AFP elevation in neonatal cholestasis due to metabolic disorders and idiopathic neonatal hepatitis and its association with steatosis and AST elevation.

Thromboembolic events are one of the important extraintestinal manifestations of inflammatory bowel diseases that are associated with considerable morbidity and mortality. Iliac vein thrombosis is rarely reported in inflammatory bowel diseases. A 9.5 year-old girl was presented with joint pain, nausea, vomiting and weight loss. She was diagnosed with Crohn's disease and right internal iliac vein thrombosis. With the implementation of immunosuppressive and anticoagulant therapies clinical picture has improved and thrombosis has resolved. Timely diagnosis and early treatment of extraintestinal complications of inflammatory bowel diseases might be lifesaving.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal, severe condition of hyperinflammation caused by the uncontrolled proliferation of activated lymphocytes and histiocytes secreting high amounts of inflammatory cytokines. Here we report a fatal hemophagocytic syndrome in a 11-year-old boy with a diagnosis of both Crohn's disease receiving immunosuppressive therapy and familial Mediterrenean fever. It is important to evaluate the patients with inflammatory bowel disease receiving immunosuppressive therapy presenting with unexplained fever, cytopenia, progression of organomegaly and biochemical changes for the investigation of HLH for diagnosis and treatment. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

The aim of this study was to investigate the presentation pattern of newly diagnosed celiac disease (CD) in Turkish children in the last eight years. Two hundred twenty patients with newly diagnosed CD were included. The medical records of all the patients between January 2000 and October 2008 were reviewed. The clinical spectrum was divided into three categories according to the main symptoms that led to the diagnosis: gastrointestinal presentation, non-gastrointestinal presentation, and silent cases. The mean age of the patients was 7.2 +/- 4.3 years at diagnosis. According to the presenting signs, the patients were defined as gastrointestinal presentation (129 patients, 58.6%), non-gastrointestinal presentation (76 patients, 34.6%) and silent cases (15 patients, 6.8%). This study showed that the number/percentage of CD cases who presented with non-gastrointestinal symptoms/conditions, so-called "non-gastrointestinal presentation", have been increasing in the last eight years.

Helicobacter pylori is a gram-negative, microaerophilic bacterium that colonizes human gastric mucosa and affects approximately 50% of the whole world population. It has put the blame on gastric ulcer, duodenal ulcer, chronic atrophic gastritis, mucosa-associated lymphoid tissue lymphoma and stomach adenocarcinoma, as the etiological agent. The cagA (cytotoxin-associated gene A) gene which is one of the most important virulence factors of H.pylori, encodes a 120-145 kDa protein called CagA antigen that may cause cell transformation. The prevalence of cagA positive H.pylori infections varies according to geographical area and age of the patients. Recent studies have suggested that cagA positive H.pylori strains play a role in the development of gastric carcinoma. The aim of this study was to evaluate the prevalence of cagA positive H.pylori isolates in adult and pediatric patient groups in Hacettepe University, Faculty of Medicine. The study was performed on 198 H.pylori stocked strains which have been isolated between 1997-2003 period from biopsy specimens of 107 adult and 91 pediatric patients with gastrointestinal pathology. Chromosomal DNA was extracted by the cetyltrimethyl-ammonium bromide (CTAB) method, and a 348 bp region of the cagA gene was amplified by an "in-house" polymerase chain reaction (PCR) using F1 and B1 primers (Gene Bank number: L11714 position 1231 and 1578R). The evaluation of PCR products revealed that 58.6% (116/198) of the isolates were cagA positive. The rates of cagA positive H.pylori among the adult and pediatric isolates were 62% and 55%, respectively. The present study demonstrates the prevalence of cagA in clinical isolates of H.pylori in our university hospital, and our data was found concordant with the results of studies reported from developed countries.