Genetic landscape of pediatric acute liver failure of indeterminate origin.

BACKGROUND AND AIMS: Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, the main causes are viral infections (12%-16%) and inherited metabolic diseases (14%-28%). Yet, in up to 50% of cases the underlying etiology remains elusive, challenging clinical management, including liver transplantation. We systematically studied indeterminate PALF cases referred for genetic evaluation by whole-exome sequencing (WES), and analyzed phenotypic and biochemical markers, and the diagnostic yield of WES in this condition. APPROACH AND RESULTS: With this international, multicenter observational study, patients (0-18 y) with indeterminate PALF were analyzed by WES. Data on the clinical and biochemical phenotype were retrieved and systematically analyzed. RESULTS: In total, 260 indeterminate PALF patients from 19 countries were recruited between 2011 and 2022, of whom 59 had recurrent PALF. WES established a genetic diagnosis in 37% of cases (97/260). Diagnostic yield was highest in children with PALF in the first year of life (41%), and in children with recurrent acute liver failure (64%). Thirty-six distinct disease genes were identified. Defects in NBAS (n=20), MPV17 (n=8), and DGUOK (n=7) were the most frequent findings. When categorizing, the most frequent were mitochondrial diseases (45%), disorders of vesicular trafficking (28%), and cytosolic aminoacyl-tRNA synthetase deficiencies (10%). One-third of patients had a fatal outcome. Fifty-six patients received liver transplantation. CONCLUSIONS: This study elucidates a large contribution of genetic causes in PALF of indeterminate origin with an increasing spectrum of disease entities. The high proportion of diagnosed cases and potential treatment implications argue for exome or in future rapid genome sequencing in PALF diagnostics.

Not all enteropathies are coeliac disease! Report of an infant with microvillus inclusion disease.

Primary enteropathies of infancy comprise of epithelial defects including microvillus inclusion disease, tufting enteropathy, and enteroendocrine cell dysgenesis and autoimmune enteropathies. The diseases in this group cause severe chronic (>2-3 weeks) diarrhoea starting in the first weeks of life and resulting in failure to thrive in the infant. Duodenal biopsies show moderate villous shortening together with crypt hyperplasia which are the main features causing resemblance to coeliac disease. We, hereby, report a term-born male infant of consanguineous parents. His two siblings died during infancy. He developed watery, urine-like diarrhea on the 3rd day of his life. On the postnatal 6th day he weighed 2750 grams, became dehydrated and had metabolic acidosis. Upper GI endoscopy performed on the postnatal 20th day appeared normal. Light microscopic examination of the duodenal biopsy showed moderate villous blunting, with mildly increased inflammatory cells in the lamina propria or and intraepithelial lymphocytosis. Enterocytes at the villous tips showed an irregular vacuolated appearance in the apical cytoplasm with patchy absence of the brush border demonstared by PAS and CD10. Electron microscopy revealed intracytoplasmic inclusions that were lined by intact microvilli in the apical cytoplasm of enterocytes. As he was dependent on TPN and aggressive intravenous fluid replacement he was hospitalized throughout his life. He died when he was 3 years and 4 months old. Paediatric coeliac disease is in the differential diagnosis of primary enteropathies of childhood. The differentiation lies on duodenal biopsy interpretation together with genetic analysis to detect the underlying genetic defect in childhood enteropathies.

Patterns and Grading of Gastrointestinal Graft-Versus-Host Disease: A Clinicopathologic Correlation Study.

BACKGROUND: The present study investigated gastrointestinal involvement patterns of acute graft-versus-host disease and assessed the correlation of pathologic severity with clinical grading. METHODS: Pathology reports of gastrointestinal (GI) endoscopic biopsies taken from 164 post-hematopoietic stem cell transplant patients with at least 1 endoscopic gastrointestinal biopsy diagnosed as "consistent with acute graft-versus-host disease" between 2005 and 2019 were retrieved from the automated hospital database. Endoscopic, pathologic and clinical gradings were performed using Freiburg criteria, Lerner and modified Seattle-Glucksberg grading systems, respectively. RESULTS: The majority of the patients (n = 140, 85.4%) were investigated with more than one biopsy from various gastrointestinal sites with a total of 479 biopsies: 44 (9.2%) esophagus, 90 (18.8%) stomach, 91 (19.0%) duodenum, 20 (4.2%) terminal ileum, 32 (6.7%) right colon, 87 (18.2%) left colon and, 115 (23.9%) rectum. Overall, lower gastrointestinal (n = 118/126, 93.6%) and upper gastrointestinal (n = 91/97, 93.8%) involvements were similar (P = .3). While the most severely affected site was duodenum (P = .021) in upper gastrointestinal, pathologic grades were similar in lower gastrointestinal sites, though more severe than upper gastrointestinal (P = .003). Pathologic grading had a low positive correlation with both clinical (r = 0.308, P = .001) and endoscopic grading (coefficient: 0.261, P = .003). CONCLUSION: Considering the similar graft-versus-host disease frequency of upper and lower gastrointestinal tract, distal colon evaluation with rectosigmoidoscopy seems to be a practical approach in patients with suspected gastrointestinal graft-versus-host disease. As it was positively correlated with both endoscopic and clinical grade, pathologic grading should be performed in these patients to assess gastrointestinal involvement patterns.

Co-Occurring Atypical Galactosemia and Wilson Disease.

Introduction: Classic galactosemia is a disorder of the galactose metabolism and is inherited as an autosomal recessive disease. It is caused by a complete or severe deficiency of galactose-1-phosphate uridyltransferase (GALT), and in rare cases, atypical galactosemia can manifest at older ages. Wilson disease (WD) is a disorder of the copper metabolism that, like galactosemia, is inherited as an autosomal recessive disease. Hepatic, neurological, or psychiatric symptoms can be seen, independently or in combination, and symptoms vary from family to family. We present here a patient diagnosed with both WD and galactosemia. Case Presentation: A 6-year-old girl was referred to our center with elevated transaminase levels and hepatosplenomegaly. The child, birthweight of 2,200 g, was born to first-degree consanguineous parents after a full-term uneventful pregnancy and was hospitalized in the neonatal period due to indirect hyperbilirubinemia, gastrointestinal bleeding, diarrhea lasting 2 weeks, and elevated liver enzymes. Hepatosplenomegaly was evident at the time of admission, a cataract was detected, and a neuropsychiatric evaluation revealed borderline mental capacity, as well as cognitive and speech retardation. Metabolic investigations revealed no specific findings other than trace positivity of reducing substances in the urine. A liver biopsy revealed copper accumulation in hepatocytes and low ceruloplasmin levels. Although WD was suspected in the patient, this diagnosis did not explain the intellectual disability, behavioral disorder, or cataract findings. A genetic analysis revealed homozygous mutations in the ATP7B and GALT genes. The galactose-1-phosphate uridyltransferase enzyme level was found to be low, and the patient was diagnosed with coexisting WD and galactosemia. Conclusion: Coexistences of rare genetically transmitted diseases can be seen in countries where consanguineous marriages are common (Saudi Arabia, Iran, Pakistan, etc.), as in our country, Turkey.

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.

3D-reconstruction and heterotopic implantation of reduced size monosegment or left lateral segment grafts in small infants: A new technique in pediatric living donor liver transplantation to overcome large-for-size syndrome.

BACKGROUND: Monosegmental grafts and reduced left lateral segment grafts have been introduced to overcome the problems of large-for-size grafts in pediatric living donor liver transplantation. Here, we introduce a new method of reduced size monosegment or left lateral segment grafts transplanted in the right diaphragmatic fossa heterotopically in small infants. METHODS: There were 4 infants who underwent living donor liver transplantation with heterotopically implanted reduced monosegmental or left lateral segment grafts at our center. The demographic, operative, postoperative, and follow-up data of these infants were collected from our prospectively designed database and reviewed. Technical details of the donor and recipient operation are shared and a supplemental provided. RESULTS: The mean recipient age was 7.5 ± 0.9 months (range: 5-10 months), and body weight was 5.9 ± 0.7 kg (range: 4.6-7.8). Primary diagnoses of the recipients were biliary atresia (n:3) and progressive familial intrahepatic cholestasis (n:1). Mean graft-recipient weight ratio was 3.3 ± 0.2. Reduced monosegment III grafts were used in 2 cases, and reduced left lateral segment grafts were used in the other 2 patients. Bile duct reconstruction was done by Roux-en-Y hepaticojejunostomy in 3 patients and duct-to-duct anastomosis in the remaining patient. All patients recovered from the liver transplantation operation and are doing well at a mean follow-up of 8 months. CONCLUSION: Living donor liver transplantation with heterotopically implanted reduced monosegmental or left lateral segment seems feasible for the treatment of neonates and extremely small infants. Further accumulation of cases and long-term follow-up are necessary to collect data for the establishment of this treatment modality.

Duodenal bulb biopsy in the diagnostic work-up of coeliac disease.

Coeliac disease (CD) is an autoimmune enteropathy which can present with patchy mucosal lesions. The aim of the present study is to investigate the significance of duodenal bulb biopsy in the diagnostic work-up of CD in both pediatric and adult patients, and to highlight the key points for pathologists. D1 (duodenal bulb) and D2 (distal duodenum) biopsies of 153 newly diagnosed serology-positive CD patients were evaluated for villous/crypt ratio and intraepithelial lymphocyte (IEL) counts on CD3-stained slides and were classified according to Marsh. Mucosal pathology was patchy in 15% (13% only D1 and 2% only D2) of patients, and 85% of patients had diffuse mucosal pathology involving both D1 and D2 biopsies which showed concordant histology in 60% and discordant in 25% of the cases. Though majority of the patients (75%) with only D1 involvement were pediatric cases, no significant difference was found between pediatric and adult patients when all cases were considered (17 vs 14%). Our results clearly indicate that without D1 sampling, diagnosis of CD would have been missed in a significant number of cases (13%), thereby highlighting the importance of taking duodenal biopsies from multiple sites in the diagnostic work-up of CD. We, therefore, conclude that every biopsy piece from both D1 and D2 should be carefully evaluated for the whole spectrum of mucosal changes caused by gluten ingestion and classified using a scheme based on Marsh to allow recognition of mild lesions.

Transaldolase haploinsufficiency in subjects with acetaminophen-induced liver failure.

Transaldolase (TAL) is an enzyme in the pentose phosphate pathway (PPP) that generates NADPH for protection against oxidative stress. While deficiency of other PPP enzymes, such as transketolase (TKT), are incompatible with mammalian cell survival, mice lacking TAL are viable and develop progressive liver disease attributed to oxidative stress. Mice with homozygous or heterozygous TAL deficiency are predisposed to cirrhosis, hepatocellular carcinoma (HCC) and acetaminophen (APAP)-induced liver failure. Both mice and humans with complete TAL deficiency accumulate sedoheptulose 7-phosphate (S7P). Previous human studies relied on screening patients with S7P accumulation, thus excluding potentially pathogenic haploinsufficiency. Of note, mice with TAL haploinsufficiency are also predisposed to HCC and APAP-induced liver failure which are preventable with oral N-acetylcysteine (NAC) administration. Based on TALDO1 DNA sequencing, we detected functional TAL deficiency due to novel, heterozygous variations in two of 94 healthy adults and four of 27 subjects with APAP-induced liver failure (P = .022). The functional consequences of these variations were individually validated by site-directed mutagenesis of normal cDNA and loss of activity by recombinant enzyme. All four patients with TAL haplo-insufficiency with APAP-induced liver failure were successfully treated with NAC. We also document two novel variations in two of 15 children with previously unexplained liver cirrhosis. Examination of the National Center for Biotechnology Information databases revealed 274 coding region variations have been documented in 1125 TALDO1 sequences relative to 25 variations in 2870 TKT sequences (P < .0001). These findings suggest an unexpected prevalence and variety of genetic changes in human TALDO1 with relevance for liver injury that may be preventable by treatment with NAC.

Novel mutations of SAR1B gene in four children with chylomicron retention disease.

BACKGROUND: Intestinal lipid malabsorption, resulting from an impaired formation or secretion of chylomicrons and associated with severe hypobetalipoproteinemia (HBL), may be due to biallelic mutations in APOB (homozygous FHBL type-1), MTTP (abetalipoproteinemia), or SAR1B (chylomicron retention disease). OBJECTIVE: We investigated four children, each born from consanguineous parents, presenting with steatorrhea, malnutrition, accumulation of lipids in enterocytes, and severe hypocholesterolemia with an apparent recessive transmission. METHODS: We sequenced a panel of genes whose variants may be associated with HBL. RESULTS: Case 1, a 9-month-old male, was found to be homozygous for a SAR1B variant (c.49 C>T), predicted to encode a truncated Sar1b protein devoid of function (p.Gln17*). Case 2, a 4-year-old male, was found to be homozygous for a SAR1B missense variant [c.409 G>C, p.(Asp137His)], which affects a highly conserved residue close to the Sar1b guanosine recognition site. Case 3, a 6-year-old male, was found to be homozygous for an ∼6 kb deletion of the SAR1B gene, which eliminates exon 2; this deletion causes the loss of the ATG translation initiation codon in the SAR1B mRNA. The same homozygous mutation was found in an 11-month-old child (case 4) who was related to case 3. CONCLUSIONS: We report 4 children with intestinal lipid malabsorption were found to have chylomicron retention disease due to 3 novel variants in the SAR1B gene.

Diagnostic Workup and Micronutrient Deficiencies in Children With Failure to Thrive Without Underlying Diseases.

OBJECTIVES AND STUDY: Failure to thrive (FTT) is an interruption in the normal pattern of growth. We aimed to evaluate the clinical characteristics, underlying etiologies, diagnostic workup, and frequency of micronutrient deficiencies (MDs) in children with FTT. METHODS: This retrospective study was done with 729 children (319 male, mean age 6.8 ± 5.5 years) with FTT (weight for age <3rd percentile) who had visited the Pediatric Gastroenterology outpatient clinic between 2011 and 2016. Children who had previously known chronic diseases, inadequate intake, or inadequate absorption were excluded. Acute malnutrition was considered if weight-for-age z-scores were below -2 and height-for-age z-scores were above -2, and chronic malnutrition was defined if height-for-age z-scores were below -2. RESULTS: The malnutrition rate was 57.1% (acute: 37.8%, chronic: 19.3%). Of children, 98.7% had laboratory evaluation. We found that 1.1% of laboratory tests, 0.4% of imaging studies, 27% of endoscopic findings, and biopsy results led to a specific diagnosis, equating to a total of 1.3% of diagnostic workup leading to a diagnosis related to FTT. The causes of FTT were inadequate nutrition (61.4%), psychiatric and behavioral disorders (17.2%), endocrinologic disorders (9%), recurrent infections (6.4%), gastrointestinal diseases (1.9%), and cardiac disorders (0.1%). Vitamin A and D deficiencies were the most common MD. CONCLUSION: We showed that the most common cause of FTT is "purely nutrition" FFT because of inadequate caloric intake, and extensive diagnostic workup is rarely helpful to reveal the etiology. These results implicate the importance of clinical evaluation and anthropometry to evaluate a child with FTT.

The Frequency of Lysosomal Acid Lipase Deficiency in Children With Unexplained Liver Disease.

OBJECTIVES: Evidence suggests that lysosomal acid lipase deficiency (LAL-D) is often underdiagnosed because symptoms may be nonspecific. We aimed to investigate the prevalence of LAL-D in children with unexplained liver disease and to identify demographic and clinical features with a prospective, multicenter, cross-sectional study. METHODS: Patients (aged 3 months-18 years) who had unexplained transaminase elevation, unexplained hepatomegaly or hepatosplenomegaly, obesity-unrelated liver steatosis, biopsy-proven cryptogenic fibrosis and cirrhosis, or liver transplantation for cryptogenic cirrhosis were enrolled. A Web-based electronic data collection system was used. LAL activity (nmol/punch/h) was measured using the dried blood spot method and classified as LAL-D (<0.02), intermediate (0.02-0.37) or normal (> 0.37). A second dried blood spot sample was obtained from patients with intermediate LAL activity for confirmation of the result. RESULTS: A total of 810 children (median age 5.6 years) from 795 families were enrolled. The reasons for enrollment were unexplained transaminase elevation (62%), unexplained organomegaly (45%), obesity-unrelated liver steatosis (26%), cryptogenic fibrosis and cirrhosis (6%), and liver transplantation for cryptogenic cirrhosis (<1%). LAL activity was normal in 634 (78%) and intermediate in 174 (21%) patients. LAL-D was identified in 2 siblings aged 15 and 6 years born to unrelated parents. Dyslipidemia, liver steatosis, and mild increase in aminotransferases were common features in these patients. Moreover, the 15-year-old patient showed growth failure and microvesicular steatosis, portal inflammation, and bridging fibrosis in the liver biopsy. Based on 795 families, 2 siblings in the same family were identified as LAL-D cases, making the prevalence of LAL-D in this study population, 0.1% (0.125%-0.606%). In the repeated measurement (76/174), LAL activity remained at the intermediate level in 38 patients. CONCLUSIONS: Overall, the frequency of LAL-D patients in this study (0.1%) suggests that LAL-D seems to be rare even in the selected high-risk population.

Multiple Presentations of LRBA Deficiency: a Single-Center Experience.

INTRODUCTION: LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency categorized as common variable immunodeficiency associated with autoimmune manifestations and inflammatory bowel diseases; however, the clinical spectrum has been extended. Here, we present our cohort of Turkish LRBA-deficient patients from a single center, demonstrating a diversity of clinical manifestations. METHOD: Seven affected individuals from five families were assessed retrospectively in this study. RESULTS: Of the seven patients with LRBA deficiency, four had homozygous, and two had compound heterozygous mutations. One patient remained disease free until the last follow-up (age 17 years). The most common clinical manifestations of the six symptomatic patients were organomegaly (6/6), autoimmunity (6/6), and chronic diarrhea (5/6). Recurrent infectious episodes were observed in three patients. None of the patients had hypogammaglobulinemia at presentation. B cell subpopulation analysis revealed low numbers of switched-memory B cell numbers in two of the four tested patients. During the disease course, three of the patients died, two of them underwent successful hematopoietic stem cell transplantation (HSCT) from matched sibling donors, and one is under abatacept therapy. CONCLUSION: LRBA defects should always be kept in mind as a differential diagnosis for patients with autoimmune disease affecting multiple organs, chronic diarrhea, and organomegalies. In our experience, early HSCT is a life-saving therapeutic strategy.

Diagnosis of celiac disease and applicability of ESPGHAN guidelines in Mediterranean countries: a real life prospective study.

BACKGROUND: We assessed how the diagnosis of Celiac Disease (CD) is made and how the new ESPGHAN guidelines can be applied in children from countries with different resources. METHODS: A real life prospective study was performed in 14 centres of 13 different Mediterranean countries. Participants were asked to apply the usual diagnostic work-up for CD according to their diagnostic facilities. RESULTS: There were 1974 patients enrolled in the study, mean age 4 years, 10 months; 865 male, 1109 female. CD was confirmed in 511 (25.9%) and was unconfirmed in 1391 (70.5%) patients; 14 patients were diagnosed as having CD according to the new ESPGHAN guidelines, 43 patients were classified as having potential CD. In all participating countries the diagnosis of CD relied on histology of duodenal biopsy; in 5 countries, HLA, and in one country endomysial antibodies (EMA) were not available. Symptoms did not add a significant increase to the pre-test probability of serological tests. The positive predictive value of tissue transglutaminase type 2 (tTG) antibodies performed with different kits but all corresponding to those recommended by ESPGHAN was 96.1% (95% CI 94-97.9%) in presence of tTG > 10xULN. In 135 patients with tTG >10xULN, HLA genotyping was performed and in all it was compatible with CD. CONCLUSIONS: The results of our study show that CD diagnosis still relies on intestinal biopsy in the Mediterranean area. New ESPGHAN criteria are not applicable in 5 countries due to lack of resources needed to perform HLA genotyping and, in one country, EMA assay. Further simplification of the new ESPGHAN guidelines might be made according to what preliminarily the present results suggest if confirmed by new prospective studies.

Response to Anastrozole Treatment in a Case with Peutz-Jeghers Syndrome and a Large Cell Calcifying Sertoli Cell Tumor.

Peutz-Jeghers syndrome (PJS) is inherited as an autosomal dominant trait characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous pigmentation, and an increased risk of neoplasm. Large-cell calcifying Sertoli cell tumor (LCCSCT) is a kind of sex cord-stromal tumor which may co-exist with PJS and which is characterized radiologically by calcification foci within the testes. Surgical treatment options for this tumor range from testis-preserving surgery to radical orchiectomy. Not with standing this invasive approach, recently, there are some case reports demonstrating the efficacy of aromatase inhibitors in avoiding orchiectomy and its associated complications. In this paper, we have presented a LCCSCT case diagnosed in a boy with PJS and his response to anastrozole treatment.

Classification chaos in coeliac disease: Does it really matter?

The spectrum of mucosal pathology in coeliac disease (CD), initially defined by Marsh in 1992 has been subjected to several modifications in the following years by Oberhuber, then by Corazza and Villanaci, and finally by Ensari. The present study, aimed to end the ongoing confusion regarding the classification of mucosal pathology in CD by applying all the classifications proposed so far on a large series of cases. A total of 270 duodenal biopsies taken from the distal duodenum of patients with a diagnosis of CD were included in the study. All biopsies were classified according to Marsh, Oberhuber, Corazza Villanaci, and Ensari classification schemes. For statistical analyses cases were divided into three groups: Group 1 included type 1 lesions in Marsh, Ensari, and Oberhuber and grade A in Corazza Villanaci classifications. Group 2 comprised of type 2 lesions in Marsh and Ensari classifications together with type2, type 3a and 3b lesions in Oberhuber classification and grade B1 lesions in Corazza Villanaci classification. Group 3 included type 3 lesions in Marsh and Ensari classifications, and type 3c lesions in Oberhuber, and grade B2 lesions in Corazza Villanaci classifications. The kappa value was 1.00 (excellent) for group 1, 0.53 (fair) for group 2 and 0.78 (excellent) for group 3 (p<0.0001). These results suggest that any of the above classification system would serve similar purposes in the diagnosis of CD. Therefore, it is advisable that the pathologist should use the simplest reliable scheme.

Lipomatous hypertrophy of the interatrial septum in a child with atrial tachycardia.

A 13-year-old girl who had been on home parenteral nutrition for 6 months has been presented with multifocal atrial tachycardia and atrial fibrillation. Echocardiography and multislice computed tomography showed fat accumulation on the interatrial septum. Lipomatous hypertrophy of the interatrial septum has never been reported in children.

Mesalamine Intolerance in Three Children with Crohn's Disease.

OBJECTIVE: To present the mesalamine-induced acute exacerbation of symptoms and inflammatory markers in children with Crohn's disease (CD). CLINICAL PRESENTATION AND INTERVENTION: Three children who presented with CD had acute exacerbation of colitis symptoms or elevated inflammatory markers when mesalamine was added to treatment while tapering/ceasing steroid treatment. While on steroid treatment, the patients maintained clinical and laboratory remission, but with the initiation of mesalamine treatment, they had abdominal pain and bloody mucoid diarrhoea and/or elevation of white blood cell count, C-reactive protein level and erythrocyte sedimentation rate. Bacterial pathogens were excluded from the urine, throat and blood cultures, parasites with stool examination, viral pathogens with serology. Within 3-7 days after the mesalamine treatment had been stopped, the patients showed improvement of colitis symptoms and normalisation of white blood cell count, C-reactive protein level and erythrocyte sedimentation rate. CONCLUSION: In this study mesalamine mimicked CD relapse in children with CD while tapering or after stopping steroid treatment. Awareness of this side effect of mesalamine could prevent a misdiagnosis of steroid dependency.