Publications by authors named "Badr Alsaleem"

14 Publications

  • Page 1 of 1

Prevalence of nutritional disorders in Saudi children with inflammatory bowel disease based on the national growth reference.

Arab J Gastroenterol 2020 Sep 11;21(3):179-182. Epub 2020 Aug 11.

Department of Paediatrics, Gastroenterology Unit, Head Paediatric IBD Research Group, King Saud University, Riyadh, Saudi Arabia.

Background And Study Aim: The prevalence of nutritional disorders in Saudi children with inflammatory bowel diseases (IBDs) has been reported using the World Health Organization (WHO) reference. Our aim was to provide more accurate definition of the prevalence of nutritional impairment in Saudi children with IBDs based on the national growth reference and to demonstrate the effect of using a reference from other populations on the prevalence rates.

Patients And Methods: Weight, height, and body mass index data, from the multicenter study of IBDs in Saudi children and adolescents, were plotted on the new Saudi national growth reference. Statistical analyses included frequency calculations and z-test for proportions to investigate the significance of the difference in prevalence. A p-value of < 0.05 was considered significant.

Results: Among a total of 374 patients, 119 (32%) had ulcerative colitis (UC) and 255 (68%) had Crohn's disease (CD). Compared with the WHO reference, the Saudi national reference produced a significantly lower prevalence of thinness in patients with UC (24% vs. 8%, p = 0.001), CD (35% vs. 20%, p = 0.002), and of short stature in patients with CD (28% vs. 11%, p < 0.001). The difference in the prevalence of overweight was not significant.

Conclusions: We provide more accurate prevalence estimate of nutritional disorders in Saudi children with IBDs based on national reference. The use of the WHO reference overestimated the prevalence of thinness and short stature in Saudi children. Prevalence estimates based on references from other populations should be interpreted with caution.
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http://dx.doi.org/10.1016/j.ajg.2020.07.002DOI Listing
September 2020

Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics.

Genome Biol 2020 06 17;21(1):145. Epub 2020 Jun 17.

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Background: At least 50% of patients with suspected Mendelian disorders remain undiagnosed after whole-exome sequencing (WES), and the extent to which non-coding variants that are not captured by WES contribute to this fraction is unclear. Whole transcriptome sequencing is a promising supplement to WES, although empirical data on the contribution of RNA analysis to the diagnosis of Mendelian diseases on a large scale are scarce.

Results: Here, we describe our experience with transcript-deleterious variants (TDVs) based on a cohort of 5647 families with suspected Mendelian diseases. We first interrogate all families for which the respective Mendelian phenotype could be mapped to a single locus to obtain an unbiased estimate of the contribution of TDVs at 18.9%. We examine the entire cohort and find that TDVs account for 15% of all "solved" cases. We compare the results of RT-PCR to in silico prediction. Definitive results from RT-PCR are obtained from blood-derived RNA for the overwhelming majority of variants (84.1%), and only a small minority (2.6%) fail analysis on all available RNA sources (blood-, skin fibroblast-, and urine renal epithelial cells-derived), which has important implications for the clinical application of RNA-seq. We also show that RNA analysis can establish the diagnosis in 13.5% of 155 patients who had received "negative" clinical WES reports. Finally, our data suggest a role for TDVs in modulating penetrance even in otherwise highly penetrant Mendelian disorders.

Conclusions: Our results provide much needed empirical data for the impending implementation of diagnostic RNA-seq in conjunction with genome sequencing.
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http://dx.doi.org/10.1186/s13059-020-02053-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298854PMC
June 2020

Liver Failure Among Young Saudi Infants: Etiology, Clinical Presentation, and Outcome.

J Pediatr Gastroenterol Nutr 2020 02;70(2):e26-e32

Division of Pediatric Gastroenterology, Children's Specialized Hospital.

Objectives: The published data on early infantile liver failure (EILF) are scarce and limited to Caucasians. We conducted this study to describe the etiology and outcome of EILF among Arabs and identify prognostic factors.

Methods: We retrospectively reviewed our database of 524 infants presenting with liver impairment from 2008 to 2018, and identified cases of EILF defined as presence of biochemical pattern of liver disease and INR ≥2 (unresponsive to vitamin K) with onset before 3 months of life. Primary outcomes included death or liver transplantation (LT) (poor outcome group) and survival with native liver (good outcome group).

Results: Forty-two cases of EILF (22 girls) were identified (8%). The etiology was indeterminate in 14 (33.3%) and established in 27 (64.3%): galactosemia (7 cases, 16.6%), tyrosinemia (5, 12%), neonatal hemochromatosis (NH), and hemophagocytic lymphohistiocytosis (HLH) (4 each, 9.5%]) mitochondrial hepatopathy (3, 7%), and miscellaneous (5, 12%). LF resolved in 15 cases (35.7%), either spontaneously or in response to specific therapy, 23 (54.7%) died, and 4 underwent LT (9.5%). ROC analysis for the best cut-off value of serum total bilirubin for prediction of study outcomes was 120 μmol/L (sensitivity 81.5%, specificity 80%). Among the diagnostic groups, galactosemia and tyrosinemia predicted good outcome, whereas the idiopathic diagnosis predicted poor outcome (OR = 13).

Conclusions: Similar to Western countries, galactosemia, tyrosinemia, NH, HLH, and mitochondrial hepatopathy are the main players in EILF in Saudi Arabia. Galactosemia and tyrosinemia predict good prognosis and idiopathic diagnosis predicts poor prognosis.
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http://dx.doi.org/10.1097/MPG.0000000000002554DOI Listing
February 2020

What Do Saudi Children Ingest?: A 10-Year Retrospective Analysis of Ingested Foreign Bodies From a Tertiary Care Center.

Pediatr Emerg Care 2019 Jul 24. Epub 2019 Jul 24.

Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City.

Objectives: Few studies investigated the correlation between foreign body (FB) ingestion and occurrence of complications. The local literature is limited to case reports and small case series on esophageal FBs. We conducted this study to identify the high-risk factors predisposing to complications among Saudi children ingesting FBs.

Methods: The medical records of 436 children (boys, 59.6%; mean age, 4.4 ± 2.7 years) presenting to the emergency department (ED) between 2007 and 2016 were retrospectively reviewed. Relative risk analysis of clinical variables was performed between 2 groups: The first group constituted children without FB-related complications (n = 389), and the second group included those with major complications (n = 14). Major complication was defined as any event associated with significant morbidity such as esophageal stricture, esophageal perforation, esophageal fistula, and intestinal perforation or fistula formation.

Results: Most of the 436 cases presented between ages 2 and 4 years (35.1%). Coin was the most commonly ingested FB (22.9%) followed by button battery (19.5%). Most of the ingested FBs passed spontaneously without intervention (69%). Upper endoscopy was performed in 121 cases (27.7%). By multivariate analysis, the variables that were significantly associated with major complications included the following: very young age group (0-2 years; odds ratio [OR], 11.5), button battery (OR, 4), FB impacted at upper esophagus (OR, 8.7), and longer time duration to visit the ED (OR, 14.7).

Conclusion: Button battery impaction at upper esophagus in very young children and delayed presentation to the ED were the most significant risk factors of FB-related complications.
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http://dx.doi.org/10.1097/PEC.0000000000001894DOI Listing
July 2019

Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies.

Genome Med 2019 06 17;11(1):38. Epub 2019 Jun 17.

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Diagnosis of primary immunodeficiencies (PIDs) is complex and cumbersome yet important for the clinical management of the disease. Exome sequencing may provide a genetic diagnosis in a significant number of patients in a single genetic test.

Methods: In May 2013, we implemented exome sequencing in routine diagnostics for patients suffering from PIDs. This study reports the clinical utility and diagnostic yield for a heterogeneous group of 254 consecutively referred PID patients from 249 families. For the majority of patients, the clinical diagnosis was based on clinical criteria including rare and/or unusual severe bacterial, viral, or fungal infections, sometimes accompanied by autoimmune manifestations. Functional immune defects were interpreted in the context of aberrant immune cell populations, aberrant antibody levels, or combinations of these factors.

Results: For 62 patients (24%), exome sequencing identified pathogenic variants in well-established PID genes. An exome-wide analysis diagnosed 10 additional patients (4%), providing diagnoses for 72 patients (28%) from 68 families altogether. The genetic diagnosis directly indicated novel treatment options for 25 patients that received a diagnosis (34%).

Conclusion: Exome sequencing as a first-tier test for PIDs granted a diagnosis for 28% of patients. Importantly, molecularly defined diagnoses indicated altered therapeutic options in 34% of cases. In addition, exome sequencing harbors advantages over gene panels as a truly generic test for all genetic diseases, including in silico extension of existing gene lists and re-analysis of existing data.
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http://dx.doi.org/10.1186/s13073-019-0649-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572765PMC
June 2019

Diagnostic delay of pediatric inflammatory bowel disease in Saudi Arabia.

Saudi J Gastroenterol 2019 Jul-Aug;25(4):257-261

Department of Pediatrics, Division of Gastroenterology and Prince Abdullah Bin Khalid Celiac Disease Research Chair, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Background/aim: Delay in the diagnosis of inflammatory bowel disease (IBD) is associated with complications. Our aim was to describe the pattern and risk factors associated with delay in the diagnosis of IBD in Saudi children.

Patients And Methods: This was a multicenter study with a retrospective/prospective design. Data on diagnostic delay in children with Crohn's disease (CD) and ulcerative colitis (UC) were retrieved from physician's notes. Multivariate regression analysis was used to assess the risk factors associated with long delay in diagnosis.

Results: There were 240 and 183 Saudi children with CD and UC, respectively. The median delays in diagnosis were 8 and 5 months in CD and UC, respectively, significantly longer in children with CD than UC (P < 0.001). Long diagnostic delays (>75 percentile) were 24 and 8.8 months for CD and UC, respectively. Ileal location was a significant risk factor in CD and the age of onset above 10 years was protective in UC.

Conclusions: Long diagnostic delay in IBD was mainly due to the longer delay in gastroenterologist consultation. Review of the referral system is needed to focus on measures to reduce long delays in diagnosis. The ileal location as a risk factor in CD and age older than 10 years as protective in UC should help recognition and early referral.
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http://dx.doi.org/10.4103/sjg.SJG_457_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714469PMC
April 2020

Unusual Manifestation of Ulcerative Colitis.

Case Rep Pediatr 2019 31;2019:5163213. Epub 2019 Jan 31.

Pediatric Gastroenterology Division, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

The relationship of inflammatory bowel disease (IBD) and chronic recurrent multifocal osteomyelitis (CRMO) is understood as extraintestinal rheumatic manifestations. CRMO is a chronic, relapsing, inflammatory, noninfectious disorder of the skeletal system of unknown origin. The disease course is not always recurrent. The association of CRMO and ulcerative colitis (UC) is very rarely reported. We report a case of a 10-year-old Saudi female who was diagnosed with CRMO, when she developed fever in association with left foot pain, and ulcerative colitis was confirmed endoscopically and histologically based on a previous settled diarrheal illness and severe iron deficiency anemia which required blood. Both conditions responded well to IBD therapy. To the best of our knowledge, this is the first reported case of chronic, multifocal osteomyelitis associated with pediatric UC in Saudi Arabia. This report supports the use of IBD therapy in treating CRMO.
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http://dx.doi.org/10.1155/2019/5163213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374790PMC
January 2019

Outcome of biliary atresia among Saudi children: A tertiary care center experience.

Saudi J Gastroenterol 2019 May-Jun;25(3):176-180

Division of Pediatric Gastroenterology, Department of Pediatric Sub-Specialities, The Children's Specialized Hospital, King Fahad Medical City; College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia.

Background/aims: Data from Western countries indicate that biliary atresia (BA) is the leading cause of end-stage liver disease in children and the most common indication for liver transplantation (LT) in the pediatric population. There is no data on the epidemiology and outcome of BA in Saudi Arabia. The main objective of our study was to understand the clinical and epidemiological characteristics and outcome of BA in the Saudi population.

Patients And Methods: We retrospectively reviewed the database of infantile cholestasis cases that presented to our center from 2008 to 2015 and identified BA cases. Data on clinical, biochemical, imaging, and histopathological characteristics were collected by chart review. The two primary study outcomes were (1) successful Kasai portoenterostomy (KPE) defined as resolution of jaundice (total serum bilirubin <20 μmol/L) and (2) survival with native liver.

Results: Over the study period, we evaluated 450 cases of infantile cholestasis. In all, 21 cases (11 males) were diagnosed with BA (4.7%). BA cases were first seen by pediatric gastroenterologists at a median age of 65 days. KPE was performed in 12 cases at a median age of 73 days. Successful KPE was achieved in four cases (33%). Five of the remaining eight cases had LT and three died before LT. Nine of the 21 BA cases were denied KPE and had primary LT at median 8 months of age. The native liver 4-year survival rate was 14.3% and the overall survival rate was 81%.

Conclusion: BA is an uncommon cause of infantile cholestasis in Saudi Arabia. Our study provides a snapshot of the epidemiology of BA in Saudi Arabia that is characterized by late referral to pediatric gastroenterologists and poor outcome without LT.
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http://dx.doi.org/10.4103/sjg.SJG_306_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526739PMC
April 2020

Biallelic mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation.

Science 2018 08 19;361(6404):810-813. Epub 2018 Jul 19.

Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.

RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system.
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http://dx.doi.org/10.1126/science.aar2641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529353PMC
August 2018

Microvillus Inclusion Disease Variant in an Infant with Intractable Diarrhea.

Case Rep Gastroenterol 2017 Sep-Dec;11(3):647-651. Epub 2017 Nov 2.

Department of Pediatric Gastroenterology and Department of Pathology, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

Microvillus inclusion disease (MVID) is a rare autosomal recessive congenital enteropathy characterized by intractable secretory diarrhea. We report a case of MVID variant with a homozygous gene mutation in syntaxin 3 . The patient is a male Saudi infant who presented shortly after birth with severe vomiting, metabolic acidosis, and mild diarrhea. Electron microscopy study for small intestinal biopsy was consistent with MVID. MYO5B gene mutation was excluded; subsequently, whole exome sequencing (WES) was performed, which revealed homozygous gene mutation in . Using WES in clinical environment can be a useful tool for diagnosing difficult and rare inherited congenital enteropathies.
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http://dx.doi.org/10.1159/000479624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731099PMC
November 2017

Bile Acid Synthesis Disorders in Arabs: A 10-year Screening Study.

J Pediatr Gastroenterol Nutr 2017 12;65(6):613-620

Pediatric Hepatology and Pediatric Liver Transplantation Unit and National Reference Centre for Rare Pediatric Liver Diseases, Hepatinov, Bicêtre Universitary Hospital, University of Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre.

Objectives: Early diagnosis of bile acid synthesis disorders (BASDs) is important because, untreated, these conditions can be fatal. Our objectives were to screen children with cholestasis or unexplained liver disease for BASD and in those with confirmed BASD to evaluate the effectiveness of cholic acid therapy.

Methods: A routine serum total bile acid measurement was performed on children with cholestasis, liver cirrhosis, and liver failure. Patients were screened for BASD by fast atom bombardment ionization-mass spectrometry (FAB-MS) analysis of urine, and molecular analysis confirmed diagnosis. Treatment response to oral cholic acid (10-15 mg/kg bw/day) was assessed from liver function tests and fat-soluble vitamin levels. FAB-MS analysis of urine was used to monitor compliance and biochemical response.

Results: Between 2007 and 2016, 626 patients were evaluated; 450 with infantile cholestasis. Fifteen cases of BASD were diagnosed: 12 presented with infantile cholestasis (2.7%, 7 boys), an 8-year-old boy presented with cirrhosis, and two 18-month-old boys presented with hepatomegaly and rickets. Eleven were caused by 3β-hydroxy-Δ-C27-steroid oxidoreductase dehydrogenase deficiency, 3 from Δ-3-oxosteroid 5β-reductase deficiency, and 1 had Zellweger spectrum disorder. In all but 1, serum total bile acids were normal or low. With cholic acid therapy, 10 are alive and healthy with their native liver. Liver failure developed in 3 infants despite therapy; 2 died and 1 underwent liver transplantation.

Conclusions: BASDs are rare but treatable causes of metabolic liver disease in Saudi Arabia. BASD should be considered in infants with cholestasis and low or normal serum total bile acid concentrations.
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http://dx.doi.org/10.1097/MPG.0000000000001734DOI Listing
December 2017

Nonfamilial Juvenile Polyposis Syndrome with Exon 5 Novel Mutation in SMAD 4 Gene.

Case Rep Pediatr 2017 27;2017:5321860. Epub 2017 Mar 27.

Pediatric Gastroenterology and Hepatology Division, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder, characterized by multiple juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. JPS is most frequently caused by mutations in the SMAD4 or BMPR1A genes. Herein, we report a child with juvenile polyposis syndrome (JPS) with a novel mutation in the SMAD4 gene. An 8-year-old boy presented with recurrent rectal bleeding and was found to have multiple polyps in the entire colon. The histology of the resected polyps was consistent with juvenile polyps. Subsequent genetic screening revealed a novel mutation in SMAD4, exon 5 (p.Ser144Stop). To the best of our knowledge, this mutation has not been reported before. Offering genotypic diagnosis for patients with JPS is an important step for strategic plan of management.
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http://dx.doi.org/10.1155/2017/5321860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385889PMC
March 2017

Corrigendum to "Nonfamilial Juvenile Polyposis Syndrome with Exon 5 Novel Mutation in SMAD 4 Gene".

Case Rep Pediatr 2017 14;2017:9861278. Epub 2017 Nov 14.

Pediatric Gastroenterology and Hepatology Division, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

[This corrects the article DOI: 10.1155/2017/5321860.].
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http://dx.doi.org/10.1155/2017/9861278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733755PMC
November 2017

Clinical and molecular characteristics of mitochondrial DNA depletion syndrome associated with neonatal cholestasis and liver failure.

J Pediatr 2014 Mar 8;164(3):553-9.e1-2. Epub 2013 Dec 8.

Newcastle Mitochondrial Highly Specialized Services Diagnostic Laboratory, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, United Kingdom.

Objective: To determine the frequency of mitochondrial DNA depletion syndrome (MDS) in infants with cholestasis and liver failure and to further clarify the clinical, biochemical, radiologic, histopathologic, and molecular features associated with MDS due to deoxyguanosine kinase (DGUOK) and MPV17 gene mutations.

Study Design: We studied 20 infants with suspected hepatocerebral MDS referred to our tertiary care center between 2007 and 2013. Genomic DNA was isolated from blood leukocytes, liver, and/or skeletal muscle samples by standard methods. Mitochondrial DNA copy number relative to nuclear DNA levels was determined in muscle and/or liver DNA using real-time quantitative polymerase chain reaction and compared with age-matched controls. Nuclear candidate genes, including polymerase γ, MPV17, and DGUOK were sequenced using standard analyses.

Results: We identified pathogenic MPV17 and DGUOK mutations in 11 infants (6 females) representing 2.5% of the 450 cases of infantile cholestasis and 22% of the 50 cases of infantile liver failure referred to our center during the study period. All of the 11 patients manifested cholestasis that was followed by a rapidly progressive liver failure and death before 2 years of life. Mitochondrial DNA depletion was demonstrated in liver or muscle for 8 out of the 11 cases where tissue was available. Seven patients had mutations in the MPV17 gene (3 novel mutations), 4 patients had DGUOK mutations (of which 2 were novel mutations).

Conclusion: Mutations in the MPV17 and DGUOK genes are present in a significant percentage of infants with liver failure and are associated with poor prognosis.
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http://dx.doi.org/10.1016/j.jpeds.2013.10.082DOI Listing
March 2014