Mutation spectrum of Tyrosinemia type I in Iran, A retrospective cohort study.

Hereditary Tyrosinemia Type 1 (HT1) is a genetic disorder characterized by an autosomal recessive inheritance pattern, caused by mutations in the fumarylacetoacetate hydrolase (FAH) gene, which results in a deficiency of fumarylacetoacetase. In our study, we identified a total of 15 mutations, including 12 newly discovered and 3 previously reported pathogenic mutations, in a cohort of 19 Iranian patients with the acute form of HT1. Out of the 12 novel variants identified, 11 were missense variants: p.Asp126His, p.Gln75Glu, p.Leu385Pro, p.Ser92Thr, p.Leu96Arg, p.Val167Glu, p.Ala94Asp, p.Gly353Trp, p.Ser164Pro, p.Glu86His and p.Ala163Pro. Additionally, there was one nonsense variant, p.Try244X, that had not been previously reported. Interestingly, the Arg237X variant was found to be particularly prevalent in this study. Notably, three exons, namely exons 9, 3, and 6, exhibited a higher frequency of mutations. All of the identified variants are presumed to result in loss of function, impacting the clinical signs, disease progression, increasing tyrosine level, and the specific location of the mutation. Our study has provided valuable insights into the mutation spectrum of variants associated with HT1 disease which is reported for the first time from Iran. This information can facilitate the development of targeted mutation screening protocols, focusing on the most prevalent mutations within specific regions or ethnic groups.

Evaluating the Association between Anemia and the Severity of Liver Disease in Children with Cirrhosis: A Cross-Sectional Study from 2015 to 2020.

Purpose: Liver cirrhosis is a major cause of hospital admission and mortality among children. Understanding the factors that influence disease severity is essential for preventing and reducing mortality. This study explored the association between hemoglobin levels and liver disease severity in children with cirrhosis. Methods: This cross-sectional study included 326 children with cirrhosis admitted to Namazi Teaching Hospital between 2015 and 2020. Clinical data, Child-Turcotte-Pugh (CTP) scores, and pediatric end-stage liver disease/model for end-stage liver disease (PELD/MELD) scores were collected to assess disease severity. Anemia was defined based on age, sex, and hemoglobin levels. Results: Among the children with cirrhosis, 275 (84.4%) were anemic, with a mean age of 5.4±4.8 years. The overall mean hemoglobin level was 9.2±2.1 g/dL. A significant inverse correlation was observed between hemoglobin levels and CTP and PELD/MELD scores in children with anemia (p<0.001). Moreover, lower hemoglobin levels were associated with more higher CTP classes (p<0.001). Conclusion: According to the data analysis, a significant correlation was observed between hemoglobin level and the severity of liver disease, and hemoglobin level decreased with increasing severity of liver disease. According to CTP class, the mean hemoglobin level decreased progressively as the disease progressed. A comparison of the mean CTP scores between children with and those without anemia revealed that those with anemia had more severe disease than those without anemia.

Comparing body composition measures in children with end stage liver disease using noninvasive bioimpedance analysis.

BACKGROUND: Chronic liver disease (CLD) in children, often leads to cirrhosis and end-stage liver disease (ESLD). CLD poses significant challenges in management and prognosis. Assessing body composition, including sarcopenia, is increasingly recognized as important in understanding outcomes in this population. METHODS: We conducted a prospective observational study, involving children aged 2 to 18 years with ESLD awaiting liver transplantation. Socio-demographic, clinical, and laboratory data were collected, and body composition was assessed using Bioelectrical Impedance Analysis (BIA). Sarcopenia was defined using age-specific cut-off points for appendicular skeletal muscle mass (aSMM) and fat-free mass (FFM). RESULTS: The study included 57 children (42.1% girls, 57.9% boys; median age: 10.9 years) with liver cirrhosis. Of them 11 (19.3%) died during the study. The mean duration of living with end-stage liver disease prior to participation was 5.43 years [IQR: 3.32, 8.39]. The most common etiology was biliary atresia (24.6%), followed by cryptogenic (22.8%). Deceased children exhibited significantly higher sarcopenia prevalence, lower basal metabolic rate and growth scores compared to survivors (P < 0.05), (771.0 vs. 934.0, P = 0.166) (65.0 vs. 80.5, P = 0.005). Total body and limb-specified lean mass were lower in deceased children, although not statistically significant. Similarly, total mineral (90% normal) and bone mineral content were lower in deceased children, with a significant difference observed only in water-to-FFM percentage (72.5 vs. 73.1, P = 0.009). CONCLUSION: This study highlights the high prevalence of sarcopenia among children with ESLD and its association with adverse outcomes, including mortality. Bioimpedance analysis emerges as a promising, non-invasive method for assessing body composition in pediatric ESLD, warranting further investigation and integration into clinical practice.

Clinical Findings, Bacterial Agents, and Antibiotic Resistance in Children with Spontaneous Peritonitis in Southern Iran: An Academic Tertiary Referral Center's Experience.

Background: Spontaneous bacterial peritonitis (SBP) is a fatal complication of ascites fluid infection. The causes of SBP in children differ from those in adults, and these bacteria are frequently resistant to antibiotics. Therefore, this study investigated the clinical findings, bacterial etiology, and antimicrobial resistance in children with SBP. Methods: This study was conducted on all new pediatric ascites patients, who were admitted to the Department of Pediatric Gastroenterology, Namazi Hospital, affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) from 2021 to 2022. Required data such as demographic information, and clinical information such as complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Gram staining, blood culture by Automated Blood Culture System (BACTEC), and antibiogram of ascites fluids by disc diffusion method were all collected. Finally, the data were statistically analyzed using SPSS Software (version 26). Besides, the t test, Fisher's exact, Mann-Whitney, and Chi square tests were used for data analysis. In all tests, P≤0.05 was considered statistically significant. Results: The present study examined 62 children with ascites of which 18 (29%) had SBP. The median (IQR) age was 2.5 (8.1) years. Thirty-four (54.8%) of the participants were girls. Abdominal pain was the most common clinical manifestation in patients (54%), and there was a significant association between abdominal pain and SBP (P=0.02). In 12 positive ascites fluid cultures, coagulase-negative staphylococci had the highest frequency (25%), followed by Escherichia coli (16.7%). Third-generation cephalosporins had a 25% sensitivity in the total positive cultures. This sensitivity was 33.3% for Gram-negative cultures and 16.6% for Gram-positive cultures. Conclusion: Although third-generation cephalosporins are recommended as the primary antibiotic for the empirical treatment of SBP, the present study found high bacterial resistance. Finally, empirical therapy should be tailored to each region's bacterial resistance features.

Impact of sarcopenia on clinical outcomes in pediatric chronic liver disease post-liver transplantation: prevalence and implications.

Aim: The purpose of this retrospective single-center study was to determine the frequency of sarcopenia and its association with mortality and other morbidities in children with chronic liver disease who had undergone liver transplantation. Background: Sarcopenia, a muscle-wasting syndrome, is common in patients with advanced liver disease and is associated with increased morbidity and mortality. While sarcopenia in adults has been extensively studied, there is little information in this regard about children and adolescents with chronic liver diseases. Methods: The study included 108 children and adolescents who had undergone liver transplantation. Sarcopenia was measured using skeletal muscle index at the third lumbar vertebral level and assessed using abdominal computed tomography imaging. Results: The frequency of sarcopenia in the studied population was found to be 45.7%. Patients with sarcopenia were more likely to be male (P<0.0001), older (P<0.0001), and had lower height-for-age z-scores (P=0.012). Genetic/metabolic diseases were the most common underlying cause of sarcopenia in children. Except for a higher rate of transplant rejection in the sarcopenia group (P=0.035), there was no significant difference in mortality rates (P=0.688) or post-LT complications between the two groups. One year after LT, computed tomography-derived body composition parameters revealed no significant differences between children who survived and those who did not. Conclusion: Our findings indicated a high frequency of sarcopenia in children with chronic liver disease, implying that more research is needed to better understand its impact on clinical outcomes in this population.

Comparison of Mir122 expression in children with biliary atresia and healthy group.

Biliary atresia (BA) is the primary cause of neonatal jaundice with various pathological mechanisms. Many BA patients may experience progressive liver dysfunction and eventually need a liver transplant. Therefore, identifying potential non-invasive biomarkers for BA is crucial. miR-122, the most abundant microRNA in the liver, plays significant roles in different liver diseases. This study aimed to assess miR-122 levels in BA patients. Eighteen patients with biliary atresia were selected at random from the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), along with 18 healthy controls. Blood samples were collected, and biochemical parameters (such as liver function tests) were measured. Quantitative reverse-transcription PCR (RT-PCR) was conducted on serum samples from both the case and control groups to analyze miR-122 levels. The study results indicated that serum miR-122 expression in BA patients was elevated compared to the control group, although it did not reach statistical significance. Additionally, no correlation was found between miR-122 expression and serum levels of liver enzymes or other laboratory findings in BA cases. miR-122 could be a potential target for diagnosing BA; however, further research with a larger population is necessary to determine if miR-122 could serve as a useful biomarker for diagnosing BA.

A Comparison of the Effect of Kegel Exercises and Conventional Therapy versus Conventional Therapy Alone in the Treatment of Functional Constipation in Children: A Randomized Clinical Trial.

Background: There have been few studies on the effect of Kegel exercises on the treatment of functional constipation in children. Hence, the present study investigated the add-on role of Kegel exercises in children with functional constipation. Methods: This clinical trial was conducted on children with functional constipation, according to Rome IV, who were referred to the pediatric department of Imam Reza Clinic (Shiraz, Iran) in 2022. The sample consisted of 64 children who were randomly assigned to either the intervention or the control groups. In the control group, a pediatrician administered conventional therapy, including diet training, defecation training, and polyethylene glycol (PEG) syrup (0.7 g/Kg daily). In the treatment group, in addition to conventional therapy, a pediatrician taught Kegel exercises to the child both verbally and in writing in the presence of their parents. To investigate the effectiveness of the intervention, frequency of defecation, defecation time, assistance used for defecation, incomplete emptying, unsuccessful defecation, abdominal pain, and painful defecation were selected as the outcomes. Independent sample t test was used for continuous variables. Categorical variables were reported as frequency and percentages. To examine the difference in categorical outcome variables, Wilcoxon (pre and post), Chi square, and Fisher exact tests were used. Data were analyzed using SPSS software version 21. P<0.05 were considered statistically significant. Results: Twenty-seven (88.4%) patients in the Kegel exercise group reported a defecation time of less than 5 min, while only 12 (37.5%) patients in the control group reached this time, and this difference was statistically significant (P=0.001). Moreover, patients in the treatment group showed significant improvements in terms of incomplete emptying of stool, unsuccessful defecation, abdominal pain, and painless defecation (P=0.001, P=0.001, P=0.001, P=0.037, respectively). After intervention, the use of laxatives, digits, or enemas to assist defecation was not significantly different between the groups (P=0.659). Conclusion: Kegel exercise was an effective adjunctive treatment for pediatric functional constipation.Trial Registration Number: IRCT20230424057984N1.

Expression of miR-let7b and miR-19b in progressive familial intrahepatic cholestasis (PFIC) children / Expresión de miR-let7b y miR-19b en niños con colestasis intrahepática familiar progresiva (PFIC)

Background MicroRNAs (miRNAs) are a group of small non-coding RNAs that bind to the target mRNA and regulate gene expression. Recently circulating microRNAs were investigated as markers of diseases and therapeutic targets. Although various studies analyze the miRNA expression in liver disease, these studies on PFIC are few. Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease with autosomal recessive inheritance. Most children with PFIC progress to cirrhosis and liver failure and consequently need to have a liver transplant. The aim of this study is the investigation of the miR-19b and miR-let7b expression levels in Iranian PFIC children. Methods 25 PFIC patients, 25 healthy children and 25 Biliary Atresia patients were considered as case and two control groups respectively. Blood samples were obtained and Liver function tests (LFTs) were measured. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for miR-19b and miR-let7b. The U6 gene is used as an internal control. Results qPCR on PFIC patients’ samples demonstrated that the miR-19b and the miR-let7b expression were significantly decreased in patients compared to the control groups, with a p-value<0.0001 and p-value=0.0006 receptively. Conclusion In conclusion, circulating micro-RNA like miR-19b and miR-let7b have a potential opportunity to be a non-invasive diagnostic marker or therapeutic target for PFIC in the future (AU)

Antecedentes Los microRNA (miRNA) son un grupo de pequeños RNA no codificantes que se unen al ARNm diana y regulan la expresión génica. Recientemente se han investigado los microRNA circulantes como marcadores de enfermedades y dianas terapéuticas. Aunque varios estudios analizan la expresión de miRNA en enfermedades hepáticas, estos estudios sobre PFIC son escasos. La colestasis intrahepática familiar progresiva (PFIC) es una enfermedad hepática rara con herencia autosómica recesiva. La mayoría de los niños con PFIC progresan a cirrosis e insuficiencia hepática y, en consecuencia, requieren de un trasplante de hígado. El objetivo de este trabajo es la investigación de los niveles de expresión de miR-19b y miR-17b en niños iraníes con PFIC. Métodos Se consideraron 25 pacientes con PFIC, 25 niños sanos y 25 pacientes con atresia biliar como grupos de casos y controles. Se obtuvieron muestras de sangre y se midieron las pruebas de función hepática (LFT). Después de la extracción de RNA y la síntesis de cDNA, se realizó PCR cuantitativa usando cebadores específicos para miR-19b y miR-17b. El gen U6 se utiliza como control interno. Resultados La qPCR en muestras de pacientes con PFIC demostró que la expresión de miR-19b y miR-17b disminuyó significativamente en los pacientes en comparación con dos grupos de control, con un valor de p<0,0001 y un valor de p=0,0006, receptivamente. Conclusión En conclusión, los micro-RNA circulantes, como miR-19b y miR-let7b, tienen una oportunidad potencial de ser un marcador de diagnóstico no invasivo o un objetivo terapéutico para PFIC en el futuro (AU)

Expression of miR-let7b and miR-19b in progressive familial intrahepatic cholestasis (PFIC) children.

BACKGROUND: MicroRNAs (miRNAs) are a group of small non-coding RNAs that bind to the target mRNA and regulate gene expression. Recently circulating microRNAs were investigated as markers of diseases and therapeutic targets. Although various studies analyze the miRNA expression in liver disease, these studies on PFIC are few. Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease with autosomal recessive inheritance. Most children with PFIC progress to cirrhosis and liver failure and consequently need to have a liver transplant. The aim of this study is the investigation of the miR-19b and miR-let7b expression levels in Iranian PFIC children. METHODS: 25 PFIC patients, 25 healthy children and 25 Biliary Atresia patients were considered as case and two control groups respectively. Blood samples were obtained and Liver function tests (LFTs) were measured. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for miR-19b and miR-let7b. The U6 gene is used as an internal control. RESULTS: qPCR on PFIC patients' samples demonstrated that the miR-19b and the miR-let7b expression were significantly decreased in patients compared to the control groups, with a p-value<0.0001 and p-value=0.0006 receptively. CONCLUSION: In conclusion, circulating micro-RNA like miR-19b and miR-let7b have a potential opportunity to be a non-invasive diagnostic marker or therapeutic target for PFIC in the future.

A pediatric case series of catastrophic gastrointestinal complications of posttransplant lymphoproliferative disease with increasing incidence, high association with coronavirus disease 2019, higher mortality, and a plea for early endoscopy to prevent late fatal outcome.

BACKGROUND: Posttransplant lymphoproliferative disorder is one of the most severe complications after transplantation, caused by uncontrolled proliferation of Epstein-Barr virus-positive B-cells in the setting of chronic immunosuppression. As one of the biggest transplant centers worldwide, we observed a potential increase in the number of patients with posttransplant lymphoproliferative disorder presenting with gastrointestinal symptoms in 1 year, during the coronavirus disease 2019 pandemic. There is limited information about dysregulation of the immune system following coronavirus disease 2019 infection, which may lead to Epstein-Barr virus reactivation in Epstein-Barr virus-positive B-cells and development of posttransplant lymphoproliferative disorder. Furthermore, there is no consensus in literature on a modality that can help in early diagnosis of posttransplant lymphoproliferative disorder with nonspecific gastrointestinal presentations before late and fatal complications occur. CASE PRESENTATION: Our case series includes five Iranian (Persian) patients, three female (2, 2.5, and 5 years old) and two male (2 and 2.5 years old), who developed gastrointestinal posttransplant lymphoproliferative disorder after liver transplantation. All of our patients were on a similar immunosuppressant regimen and had similar Epstein-Barr virus serologic status (seronegative at time of transplantation but seropositive at time of posttransplant lymphoproliferative disorder diagnosis). Four patients had either a positive coronavirus disease 2019 polymerase chain reaction test or exposure within the family. Although all of our patients presented with nonspecific gastrointestinal symptoms, four patients developed late posttransplant lymphoproliferative disorder complications such as bowel perforation and obstruction. All five patients with gastrointestinal posttransplant lymphoproliferative disorder received chemotherapy, but only two survived and currently are continuing the therapy. In one of the surviving patients, prompt endoscopic investigation resulted in early diagnosis of posttransplant lymphoproliferative disorder and a better outcome. CONCLUSION: Since 80% of our patients had exposure to coronavirus, a potential relationship might be suggested between the two. Furthermore, as we witnessed in one case, urgent endoscopic investigation in immunocompromised patients presenting with gastrointestinal symptoms can improve the clinical outcomes and therefore should be considered for early diagnosis of posttransplant lymphoproliferative disorder.

Relapse Rate of Clinical Symptoms After Stopping Treatment in Children with Cyclic Vomiting Syndrome.

Background: Cyclic vomiting syndrome (CVS) is a chronic functional gastrointestinal disorder. It is characterized by recurrent episodes of vomiting typically separated by periods of symptom-free or baseline health. The present study aimed at evaluating the effectiveness of propranolol and the relapse rate of clinical symptoms after stopping treatment in children suffering from CVS. Methods: Records of 504 patients below the age of 18 years with CVS who were treated with propranolol from March 2008 to March 2018 were reviewed. The duration of follow-up was 10 years. Results: The average age of CVS affliction was 4.3 years and the average age at the diagnosis was 5.8 years. All subjects were treated with propranolol (for an average of 10 months). 92% of treated subjects were cured, causing a dramatic decrease in the rate of vomiting (P < 0.001). Only an average of 10.5% of the studied subjects (53 people) showed a relapse of symptoms after stopping the treatment. The results of a 10-year follow-up period of the patients showed that 24 had abdominal migraine and 6 had migraine headaches, all of whom lacked the symptoms of disease relapse (prognostic evaluation). Conclusion: The findings of this investigation show that the duration of treating CVS with propranolol could be shortened to 10 months with a low percent of symptoms relapse and this shortening may be effective in preventing the undesirable side effects of the drug. The presence of abdominal migraine and migraine headaches in patients after treatment accomplishment and the lack of disease relapse can be prognostic measures for this disease, which require intensive attention.

Chylous ascites as a rare complication of abdominal trauma in a 7-year-old girl: A case report.

Key Clinical Message: Abdominal trauma can be one of the causes of chylous ascites in pediatric cases, along with tuberculosis and malignancy. However, a definitive diagnosis is more reasonable to be done by excluding other causes. Abstract: Chylous ascites (CA) is a rare type of ascites. Though it has high mortality and morbidity rates, which usually happen due to the rupture of lymph vessels into the peritoneal cavity. Congenital abnormalities, including lymphatic hypoplasia or dysplasia, are the most causes in pediatrics. CA following trauma in children is very rare, and to the best of our knowledge, there are very few reports in this regard. Here, we report a 7-year-old girl who was referred to our center with CA after a car accident.

Evaluation of Outcomes and Complications of Large Volume Paracentesis without Albumin and Coagulopathy Therapy in Pediatrics with Severe Ascites.

Background: Large-volume paracentesis has become the first treatment choice for patients with severe and refractory ascites. The studies have reported several complications after therapeutic paracentesis. But there are few published data on the complications with or without Albumin therapy. We aimed to analyze the safety and complications of large-volume paracentesis in children with or without albumin therapy. Methods: This study was conducted on children with severe ascites with chronic liver disease who underwent large-volume paracentesis. They were divided into albumin-infused and albumin non-infused groups. In the case of coagulopathy, no adjustment was made. Albumin was not administered after the procedure. The outcomes were monitored to evaluate the complications. To compare two groups, a t-test was utilized, and the ANOVA test was used to compare several groups. If the requirements for using these tests were not met, Mann-Whitney and Kruskal-Wallis tests were applied. Results: Decreased heart rate was observed in all time intervals and was meaningful six days after paracentesis. MAP also decreased statistically at 48 hours and six days after the procedure (P < 0.05). Other variables did not show any meaningful change. Conclusion: Children having tense ascites with thrombocytopenia, prolonged PT, Child-Pugh class C, and encephalopathy can undergo large-volume paracentesis without any complication. Albumin administration before the procedure in patients with low levels of Albumin (<2.9) can effectively overcome the problems of tachycardia and increased mean arterial pressure. There will be no need for Albumin administration after paracentesis.

Large Volume Paracentesis in Patients with Liver Cirrhosis Temporarily Diminishes Blood Cell Count.

Background: Large-volume paracentesis is the preferred treatment for patients with severe and refractory ascites. Several complications were reported during therapeutical paracentesis. However, there are very few published studies on the change in blood cell count after paracentesis. This study aimed to evaluate any changes in blood cell counts after ascites fluid drainage. Methods: This study was conducted on patients with severe ascites and chronic liver disease who underwent large-volume paracentesis at Namazi Hospital, in Shiraz, Iran, between March 2021 and February 2022. A data gathering form containing the patient's medical history, cause of cirrhosis, ascites fluid volume, as well as routine tests including primarily sodium, potassium, and basal creatinine, was filled out. Before and after the surgery, the total blood cell count was measured. Before the procedure, adjustment was made in the case of coagulopathy and albumin deficiency. The effect of factors such as the volume of drained fluid, splenomegaly, antibiotics, and steroid use was assessed on the changes in the number of blood cells. Using the JAMOVI 2.3.9 software, a paired t test and multiple regression were applied for statistical analysis (P<0.001). Results: The study included 37 patients. After the paracentesis procedure, the number of blood cells significantly decreased in all groups (P<0.001). The followings are the amounts of each type of blood cells before and after the procedure: Platelet=153837±91862 and 115648±69136, red blood cells=3.53±0.784 and 3.22±0.705, white blood cells=12.3±7.78 and 8.6±5.5. None of the study variables, including drained volume, splenomegaly, antibiotics, and steroid use, were significant predictors of the changes in the blood cell count after paracentesis (P>0.001). Conclusion: The findings of the present study showed that children with tense ascites who had large-volume paracentesis might experience a sharp drop in blood cell count after the procedure, which was a transient physiological condition.

Extra-intestinal manifestations of Celiac disease in children: their prevalence and association with human leukocyte antigens and pathological and laboratory evaluations.

BACKGROUND: Celiac disease (CD) is an autoimmune disease caused by gluten intake. Traditionally CD was believed to be a disease of the gut, although a wide range of extra-intestinal manifestations (EIM) was recognized. The exact prevalence of EIM and the associated risk factors have not been well studied. AIM: We aimed to assess the prevalence of EIM in children with CD and their association with human leukocyte antigen (HLA) typing, and pathological and laboratory indices. METHOD: We conducted a cross-sectional study on children and adolescents with a definite diagnosis of CD. They were followed in the main Celiac Clinic of Southern Iran. RESULTS: We included 204 children who were visited between 2012 and 2017. Nearly 85% of them were positive for HLA-DQ2 and 40.6% for HLA-DQ8. The most prevalent intestinal complaints reported were abdominal pain (42.6%) and chronic constipation (19.1%). Failure-to-thrive (32.7%), iron deficiency anemia (25%), short stature (20.5%), and eczema (18.6%) were the most common EIMs. However, failure-to-thrive and short stature were presented at significantly younger ages, whereas those patients with concomitant type 1 diabetes mellitus (DM) were significantly older. We also found significant relationships between autoimmune thyroid disease and HLA-DQ5, and the presence of headaches with HLA-DQ7. The prevalence of HLA types of DQ2, DQ8, DQ6, and DQ7 significantly varied among different Marsh groups. Patients who were positive for HLA-DQ8, were significantly older, taller, and weightier. No significant association was found between HLA types and any of the gastrointestinal symptoms, anti-tTG and compliance to gluten free diet. Moreover, there were no statistically significant differences detected between the presence of each individual EIM, the level of IgA anti-tTG, sex, and Marsh typing. CONCLUSION: This study highlights the presence of EIM in CD and their associated factors. We show the potential role of HLA typing in some EIMs, which may shed light for future studies.

Identification of a novel mutation in the ALDOB gene in hereditary fructose intolerance.

OBJECTIVES: Hereditary fructose intolerance (HFI) is caused by aldolase B enzyme deficiency. There has been no report about HFI from Iran and the type of mutations has not been reported in the Iranian population so far. CASE PRESENTATION: Herein we report a 2 year old girl presented with failure to thrive, hepatomegaly, and liver dysfunction. The primary impression has been hepatic glycogen storage disease type 1 or 6. This diagnosis was not confirmed by laboratory data and liver biopsy. Therefore, targeted-gene sequencing (TGS) covering 450 genes involved in inborn errors in metabolic diseases was performed. The results of TGS showed a rare novel homozygous pathogenic variant c.944del (p.Gly315ValfsTer15) in the ALDOB gene. CONCLUSIONS: This report introduces a novel variant that expands the mutational spectrum of the ALDOB gene in patients with HFI.

Cohort Profile: Shiraz Pediatric Liver Cirrhosis Cohort (SPLCCS).

Liver diseases in children and adolescents are a significant and arising public health issue and should be surveyed from different dimensions (clinical and para-clinical, psychological, socio-economic) and in diverse populations. Shiraz Liver Transplant Center, Shiraz, Iran is the only center for pediatric liver transplantation and its pre-operative evaluations. This provides a unique and valuable situation for studying this vulnerable population. The Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS) was established to assess cirrhotic children, the course of their disease, and treatment over time. This cohort study aimed to prospectively evaluate the natural course and factors that contributed to complications and death of children with chronic liver disease in the region. SPLCCS was launched in September 2018 after obtaining ethical approval; until August 2022, 370 children with end-stage liver disease were enrolled and followed every six months. Here, the cohort's features, the included population's baseline characteristics, and primary outcomes are reported.

Aplastic anemia: a new complication in the recent mysterious hepatitis outbreak among children worldwide: two case reports.

BACKGROUND: Recently, an unknown hepatitis outbreak among children has concerned many individuals worldwide. These cases are frequently reported, mainly from Europe and other countries. In this study, we present two similar patients, who, to the best of our knowledge, are the first cases reported in the Middle East (Shiraz, Fars Province, Iran). Unlike in similar cases reported up until 30 April 2022, our patients' hepatitis eventually resulted in aplastic anemia. CASE PRESENTATION: In this study, we present cases of two Iranian boys aged 13 and 8 years with hepatitis of unknown origin who developed aplastic anemia in the course of hospitalization. CONCLUSIONS: Hepatitis-associated aplastic anemia is a well-known immune-mediated form of aplastic anemia that we detected in our patients and treated with immunosuppressive therapy. One patient established a satisfactory response to the treatment, but unfortunately, the other was declared brain dead.

Rosa damascena together with brown sugar mitigate functional constipation in children over 12 months old: A double-blind randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa × damascena Herrm., known as damask rose, is a bushy shrub that is found abundantly in Fars province, Iran. This species has been used in Iranian traditional practices for the treatment of abdominal pain and constipation, as gastrointestinal diseases. Brown sugar (Saccharum officinarum L.) has also shown laxative effects in pediatric patients with functional constipation. AIM OF STUDY: This study aimed to compare the effects of Polyethylene Glycol (PEG) and a syrup made of R. damascena and brown sugar on the treatment of functional constipation in children aged above 12 months. MATERIALS AND METHODS: This double-blind randomized clinical trial was performed on 100 patients. One group received PEG and the other received an herbal syrup containing the decocted extract of 0.1 g R. damascena petals mixed with 0.85 g brown sugar per 1 mL. The patients were followed up for two and four weeks and their progresses were recorded. RESULTS: The cure rate was 100% in the R. damascena group and 91.7% in the control group. R. damascena and brown sugar syrup had an odds ratio of 1.09 in the treatment of functional constipation compared to PEG, but the difference was not statistically significant. The only adverse effect detected in the R. damascena group after four weeks was the bad taste of the medication that was too sweet. Nonetheless, this could be solved during the pharmaceutical processes. CONCLUSION: The R. damascena extract and brown sugar syrup can be used as an effective, safe, and inexpensive agent in the treatment of functional constipation.

An evaluation of ascitic calprotectin for diagnosis of ascitic fluid infection in children with cirrhosis.

BACKGROUND: The most common infection in children with the hepatic disease with or without cirrhotic ascites is spontaneous bacterial peritonitis (SBP), which occurs in the absence of an evident intra-abdominal source of infection. The present study aims to assess the value of calprotectin in ascitic fluid in the diagnosis of ascitic fluid infection in children with liver cirrhosis. MATERIALS AND METHODS: In this cross-section study, 80 children with underlying liver disease who attended the Hepatology and Emergency Department in Shiraz University Hospitals were studied. All the patients were evaluated by a thorough history, clinical examination, laboratory investigations, diagnostic paracentesis with PMNLs count, and Calprotectin, which was measured in 1 mL ascitic fluid by ELISA. RESULTS: Thirty-five patients (43.75%) were diagnosed with ascitic fluid infection. Of these children 6 cases had positive ascitic fluid culture (SBP). Calprotectin was high in AFI patients with a statistically significant difference in AFI patients compared to non-AFI patients. The cut-off levels were 91.55 mg /L and the area under the curve was 0.971. So it can serve as a sensitive and specific diagnostic test for detection of AFI in children with underlying liver disease. CONCLUSION: Elevated ascitic calprotectin levels in cirrhotic patients are a diagnostic and reliable marker for the detection of AFI and are considered a surrogate marker for PMN.