The impact of a gluten-free diet on the growth pattern of Saudi children with coeliac disease.

OBJECTIVE: To assess the growth pattern of children with coeliac disease after the introduction of a gluten-free diet. METHOD: The retrospective study was conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, and comprised data from January 2015 to December 2018 of children aged 2-16 years with biopsy-proven coeliac disease. Serial measurements of height-for-age and weight-for-age z-scores were recorded at 0, 4, 8, 12 and 16 months. Data on insulin-like growth factor-1 and insulin-like growth factor binding protein-3 obtained at diagnosis and during follow-up was retrieved. Clinical, demographic, and laboratory data was extracted from the patients' medical files. Data was analysed using SPSS 22. RESULTS: Of the 47 patients, 25(53.2%) were boys and 22(46.8%) were girls. The overall mean age was 8.7±3.4 years. There was a significant time effect for weight-for-age and height-for-age z-scores (p<0.001). There was significant increase in the secretion of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 (p<0.05) during the first 8 months of a gluten-free diet. CONCLUSIONS: The administration of gluten-free diet for Saudi children with coeliac disease normalized growth parameters and improved the endogenous secretion of growth factors.

Genome-Wide Association Study-Guided Exome Rare Variant Burden Analysis Identifies IL1R1 and CD3E as Potential Autoimmunity Risk Genes for Celiac Disease.

Celiac disease (CeD) is a multifactorial autoimmune enteropathy characterized by the overactivation of the immune system in response to dietary gluten. The molecular etiology of CeD is still not well-understood. Therefore, this study aims to identify potential candidate genes involved in CeD pathogenesis by applying multilayered system biology approaches. Initially, we identified rare coding variants shared between the affected siblings in two rare Arab CeD families by whole-exome sequencing (WES). Then we used the STRING database to construct a protein network of rare variants and genome-wide association study (GWAS) loci to explore their molecular interactions in CeD. Furthermore, the hub genes identified based on network topology parameters were subjected to a series of computational validation analyses like pathway enrichment, gene expression, knockout mouse model, and variant pathogenicity predictions. Our findings have shown the absence of rare variants showing classical Mendelian inheritance in both families. However, interactome analysis of rare WES variants and GWAS loci has identified a total of 11 hub genes. The multidimensional computational analysis of hub genes has prioritized IL1R1 for family A and CD3E for family B as potential genes. These genes were connected to CeD pathogenesis pathways of T-cell selection, cytokine signaling, and adaptive immune response. Future multi-omics studies may uncover the roles of IL1R1 and CD3E in gluten sensitivity. The present investigation lays forth a novel approach integrating next-generation sequencing (NGS) of familial cases, GWAS, and computational analysis for solving the complex genetic architecture of CeD.

Metabolic bone disease in children and adolescent patients with ulcerative colitis.

OBJECTIVE: Metabolic bone disease concerns a broad spectrum of conditions related to reduced bone density. Metabolic bone disease has been linked to chronic inflammatory diseases, such as ulcerative colitis. This study examines the prevalence of metabolic bone disease in ulcerative colitis patients and explores possible clinical predictors. METHOD: The authors performed a retrospective study involving children and adolescents with confirmed ulcerative colitis between January 2013 and December 2018. Bone density was evaluated through a dual-energy X-ray absorptiometry scan of the spine and total body. Osteoporosis was defined as a bone mineral density Z-score of <-2 and osteopenia as a Z-score of between -1.0 and -2. RESULTS: A total of 37 patients were included in this analysis, with a mean age of 13.4±3.9 years and a mean duration of illness of 2.1±2.4 years. Using lumbar spine Z-scores and total body Z-scores, osteoporosis and osteopenia were identified by dual-energy X-ray absorptiometry scan measurements in 11 patients (29.7%) and 15 patients (40.5%), and in ten patients (27%) and 13 patients (35%), respectively. Lumbar spine Z-scores were significantly positively associated with male gender (B=2.02; p=0.0001), and negatively associated with the presence of extraintestinal manifestations (B=-1.51, p=0.009) and the use of biologics (B=-1.33, p=0.004). However, total body Z-scores were positively associated with body mass index Z-scores (B=0.26, p=0.004) and duration of illness in years (B=0.35, p=0.003). CONCLUSIONS: Metabolic bone disease is very common in this cohort of Saudi Arabian children and adolescents with ulcerative colitis and its occurrence appears to increase in female patients who suffer from extraintestinal manifestations.

Histologically confirmed upper gastrointestinal Crohn's disease: is it rare or are we just not searching hard enough?

BACKGROUND/AIMS: Crohn's disease (CD) may involve the upper parts of the gastrointestinal (GI) tract including the esophagus, stomach, and duodenum. Clinical features of upper GI CD (UGICD) are not well characterized in the Gulf region. We therefore aimed to assess the prevalence and clinical characteristics of patients diagnosed with UGICD. METHODS: We performed a retrospective analysis of all patients diagnosed with CD who underwent upper GI endoscopy between 2012 and 2017 at King Abdulaziz University Hospital, irrespective of age. Patients who had endoscopy of the upper GI tract at baseline and had histologically confirmed UGICD were included. Data on patients' demographics, clinical characteristics, extraintestinal manifestations and complications were reviewed. RESULTS: We identified 78 CD patients who underwent upper GI endoscopy from our medical records. The mean age was 17.2±8.7 years and 55.1% were males. Of the total, 19 out of 78 patients (24.4%) had histologically confirmed UGICD (3 esophageal, 16 gastric, and 9 duodenal), of which 52.6% were symptomatic. Disease distribution was ileal in 57.8%, colonic in 21.1% and ileo-colonic in 21.1%. A non-stricturing and non-penetrating phenotype was reported in 89.4%, stricturing in 5.3%, and penetrating in 5.3%. Perianal disease was found in 10.5%. UGICD was complicated by stricture formation in 2 patients (esophageal and gastric). CONCLUSIONS: The prevalence of UGICD is considered high among CD Saudi patients who undergo upper GI endoscopy at baseline, and is asymptomatic in 47.4% of patients. This reported prevalence is not dissimilar from reports originating from Western countries.

Whole exome sequencing of a Saudi family and systems biology analysis identifies CPED1 as a putative causative gene to Celiac Disease.

Celiac disease (CD) is a gastrointestinal disorder whose genetic basis is not fully understood. Therefore, we studied a Saudi family with two CD affected siblings to discover the causal genetic defect. Through whole exome sequencing (WES), we identified that both siblings have inherited an extremely rare and deleterious CPED1 genetic variant (c.241 A > G; p.Thr81Ala) segregating as autosomal recessive mutation, suggesting its putative causal role in the CD. Saudi population specific minor allele frequency (MAF) analysis has confirmed its extremely rare prevalence in homozygous condition (MAF is 0.0004). The Sanger sequencing analysis confirmed the absence of this homozygous variant in 100 sporadic Saudi CD cases. Genotype-Tissue Expression (GTEx) data has revealed that CPED1 is abundantly expressed in gastrointestinal mucosa. By using a combination of systems biology approaches like protein 3D modeling, stability analysis and nucleotide sequence conservation analysis, we have further established that this variant is deleterious to the structural and functional aspects of CPED1 protein. To the best of our knowledge, this variant has not been previously reported in CD or any other gastrointestinal disease. The cell culture and animal model studies could provide further insight into the exact role of CPED1 p.Thr81Ala variant in the pathophysiology of CD. In conclusion, by using WES and systems biology analysis, present study for the first-time reports CPED1 as a potential causative gene for CD in a Saudi family with potential implications to both disease diagnosis and genetic counseling.

Metabolic bone disease in children and adolescent patients with ulcerative colitis

Abstract Objective: Metabolic bone disease concerns a broad spectrum of conditions related to reduced bone density. Metabolic bone disease has been linked to chronic inflammatory diseases, such as ulcerative colitis. This study examines the prevalence of metabolic bone disease in ulcerative colitis patients and explores possible clinical predictors. Method: The authors performed a retrospective study involving children and adolescents with confirmed ulcerative colitis between January 2013 and December 2018. Bone density was evaluated through a dual-energy X-ray absorptiometry scan of the spine and total body. Osteoporosis was defined as a bone mineral density Z-score of <−2 and osteopenia as a Z-score of between −1.0 and −2. Results: A total of 37 patients were included in this analysis, with a mean age of 13.4 ± 3.9 years and a mean duration of illness of 2.1 ± 2.4 years. Using lumbar spine Z-scores and total body Z-scores, osteoporosis and osteopenia were identified by dual-energy X-ray absorptiometry scan measurements in 11 patients (29.7%) and 15 patients (40.5%), and in ten patients (27%) and 13 patients (35%), respectively. Lumbar spine Z-scores were significantly positively associated with male gender (B = 2.02; p = 0.0001), and negatively associated with the presence of extraintestinal manifestations (B = −1.51, p = 0.009) and the use of biologics (B = −1.33, p = 0.004). However, total body Z-scores were positively associated with body mass index Z-scores (B = 0.26, p = 0.004) and duration of illness in years (B = 0.35, p = 0.003). Conclusions: Metabolic bone disease is very common in this cohort of Saudi Arabian children and adolescents with ulcerative colitis and its occurrence appears to increase in female patients who suffer from extraintestinal manifestations.

Nutritional status of children with inflammatory bowel disease in Saudi Arabia.

AIM: To assess the prevalence of nutritional disorders in children with inflammatory bowel disease (IBD) in Saudi Arabia. METHODS: The data from a national cohort of children newly diagnosed with IBD between 2003 and 2012 were analyzed. The diagnosis of IBD and the differentiation between Crohn's disease (CD) and ulcerative colitis (UC) were confirmed by gastroenterologists according to the standard criteria. The body mass index (BMI) of each child [weight (kg)/height(2) (m)] was calculated at the time of diagnosis. The World Health Organization standards and references were used and the BMI for age > +1 and < -2 standard deviation score were used to define overweight and thinness, respectively. Age stratification analysis was performed to investigate any age-related variation in the prevalence of nutritional status between children < 10 years of age and older. RESULTS: There were 374 children from 0.33 to 17 years of age, including 119 (32%) children with UC and 255 (68%) with CD. All of the children were Saudi nationals, and 68 (57%) of the UC and 150 (59%) of the CD children were males. A positive history of anorexia at the time of diagnosis was found in 30 (25%) patients with UC and 99 (39%) patients with CD. The prevalence of thinness was 31%, 35% and 24% in children with IBD, CD and UC, respectively, with a significantly higher prevalence of thinness in children with CD than in children with UC (P = 0.037) only in the age group of 10-17 years (P = 0.030). The prevalence of overweight was 16 %, 15% and 20 % in the children with IBD, CD and UC, respectively, indicating a higher prevalence in UC that was statistically significant only in the age group of 10-17 years (P = 0.020). CONCLUSION: A high proportion of children with IBD presented with overweight instead of the classical underweight. Awareness of this finding is important for patient care.