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 (STX3). 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 STX3. Using WES in clinical environment can be a useful tool for diagnosing difficult and rare inherited congenital enteropathies.

Cytomegalovirus (CMV) infection exists in 50-80% of the world's population in clinically undetected form due to their immunocompetent status. Here we report a case of a 42-year-old COVID-19 patient with no past medical history, who received tocilizumab, which led to a massive lower gastrointestinal bleeding not responded to medical management.

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.

Background Investigators from different parts of the world are calling for a re-evaluation of the role of liver biopsy (LB) in the evaluation of infantile cholestasis (IC), especially in the light of emerging non-invasive diagnostic technologies. Therefore, this retrospective single-center study was conducted to determine the impact of LB on the diagnosis and management of IC in a cohort from Arabs. Methods From 2007 until 2019, 533 cases of IC were referred for evaluation. All infants who underwent LB were included in the study. We categorized the yield of LB into: (1) defined specific diagnosis; (2) excluded an important diagnosis. A single pathologist reviewed and made the histology report. Results 122 LB specimens met the inclusion criteria. The main indication for LB was a high suspicion of biliary atresia (BA) [high gamma-glutamyl transferase (GGT) cholestasis and pale stool] in 46 cases (37.8%). Liver biopsy had sensitivity of 86.4%, specificity (66.7%), PPV (70.4%), NPV (84.2%) in diagnosing BA. LB had a direct impact on clinical management in 52 cases (42.6%): (1) The true diagnosis was suggested by LB in 36 cases; (2) LB excluded BA and avoided intraoperative cholangiogram in 16 cases with high suspicion of BA. Among the 76 cases with low suspicion of BA, LB suggested the true diagnosis or helped to initiate specific management in 8 cases only (10.5%). In contrast, molecular testing confirmed the diagnosis in 48 (63%). Conclusion LB continues to be an important tool in the workup of cases with a high suspicion of BA. The low yield of LB in cases with low suspicion of BA calls for a re-evaluation of its role in these cases in whom early incorporation of cholestasis sequencing gene  panels can have a better diagnostic yield.

Proprotein convertase (PC) deficiency is a rare autosomal recessive disorder caused by mutations in proprotein convertase subtilisin/kexin type 1 (PCSK1). It is characterized by severe malabsorptive early-onset diarrhea, obesity, and systemic endocrinopathies. Only few cases have been reported in the literature; we have add two female sisters with some difference in clinical progress. Herein, we describe two sisters with congenital osmotic diarrhea diagnosed with PC1/3 deficiency, causing malabsorptive diarrhea and enteroendocrine dysfunction, who presented with chronic enteropathy with hypernatremia but with different expressivity. PC1/3 deficiency presents with symptoms and signs that mimic glucose-galactose malabsorption. Because of the clinical paucity and heterogeneity of congenital enteropathies, whole-exome sequencing may be of great help towards early diagnosis and effective treatment.

Background: Trichohepatoenteric syndrome (THES) is a very rare disorder that is characterized by intractable congenital diarrhea, woolly hair, intrauterine growth restriction, facial dysmorphism, and short stature. Our knowledge of THES is limited due to the small number of reported cases. Methods: Thirty patients diagnosed with THES, all molecularly confirmed by whole exome sequencing (WES) to have biallelic variants in TTC37 or SKIV2L , were included in the study. Clinical, biochemical, and nutritional phenotypes and outcome data were collected from all participants. Results: The median age of THES patients was 3.7 years (0.9–23 years). Diarrhea and malnutrition were the most common clinical features (100%). Other common features included hair abnormalities (96%), skin hyperpigmentation (87%), facial dysmorphic abnormalities (73%), psychomotor retardation (57%), and hepatic abnormalities (30%). Twenty-five patients required parenteral nutrition (83%) with a mean duration of 13.34 months, and nearly half were eventually weaned off. Parenteral nutrition was associated with a poor prognosis. The vast majority of cases (89.6%) had biallelic variants in SKIV2L , with biallelic variants in TTC37 accounting for the remaining cases. A total of seven variants were identified in TTC37 ( n = 3) and SKIV2L ( n = 4). The underlying genotype influenced some phenotypic aspects, especially liver involvement, which was more common in TTC37 -related THES. Conclusion: Our data helps define the natural history of THES and provide clinical management guidelines.

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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