Siham Al-Sinani

Liver Disease and Other Comorbidities in Wolcott-Rallison Syndrome: Different Phenotype and Variable Associations in a Large Cohort

Background: Wolcott-Rallison syndrome (WRS) is caused by recessive EIF2AK3 mutations and characterized by early-onset diabetes and skeletal dysplasia. Hepatic dysfunction has been reported in 60% of patients. Aims: To describe a cohort of WRS patients and discuss the pattern and management of their liver disease. Methods: Detailed phenotyping and direct sequencing of EIF2AK3 gene were conducted in all patients. Results: Twenty-eight genetically confirmed patients (67% male; mean age 4.6 years) were identified. 17 different EIF2AK3 mutations were detected, of which 2 were novel. The p.S991N mutation was associated with prolonged survival and p.I650T with delayed onset. All patients presented before 25 months with diabetes with variation in the frequency and severity of 10 other features. Liver disease, first manifested as non-autoimmune hepatitis, was the commonest extra-pancreatic feature identified in 85.7% (24/28). 22/24 had at least one episode of acute hepatic failure which was the cause of death in all deceased patients (13/28). One child was treated by liver transplantation and had no liver disease and better diabetes control for the following 6 years. Conclusions: Liver disease in WRS is more frequent than previously described and carries high mortality. The first experience with liver transplantation in WRS is encouraging.

Severity ranking of non-deletional alpha thalassemic alleles: insights from an Omani family study

In an Omani family, four different alpha thalassemic alleles, one single‐gene deletional (−α3.7) and three non‐deletional forms (αTSaudi, αΔ5nt, and αΔG), interact in various combinations and result in two distinct hematological phenotypes, with and without HbH inclusions. After excluding the presence of potential genetic modifiers, viz associated β‐thalassemic alleles or functional alpha hemoglobin stabilizing protein (AHSP) polymorphisms, we observed that only the genetic combinations involving αTSaudi mutation are associated with HbH inclusions (a marker of degree of α/β‐chain imbalance) and high reticulocyte count (a marker of ongoing hemolysis). Overall, the αTSaudi mutation is associated with a more severe α‐globin deficiency than the other two (αΔ5nt and αΔG) non‐deletional α0 thalassemic mutations. The likely molecular explanation is that the compensatory increase in the linked α1 globin gene expression is much more compromised in cases with αTSaudi mutation.

Prevalence of Celiac Disease in Omani Children with Type 1 Diabetes Mellitus: A Cross Sectional Study

OBJECTIVE Published studies on the prevalence of celiac disease in type 1 diabetes mellitus from the Arab World are scant. We aim to report the prevalence of celiac disease in Omani children with type 1 diabetes mellitus. METHODS Children with type 1 diabetes mellitus were prospectively screened for celiac disease, at Sultan Qaboos University Hospital, Muscat, Oman over a period of one year (June 2011 - May 2012). Serum anti tissue transglutaminase IgA, endomysial IgA antibodies and total IgA were measured for screening of celiac disease. Children with positive anti-tissue transglutaminase and/or endomysial IgA antibodies underwent endoscopy. RESULTS A total of 103 children with type 1 diabetes mellitus were initially included. Ten patients were lost to follow up. Ninety-three patients aged 2-17 years underwent screening for celiac disease. Sixteen patients had positive anti-tissue transglutaminase (17%). Fourteen patients underwent endoscopy with duodenal biopsies, while two were lost to follow-up. Five patients with positive anti-tissue transglutaminase had intestinal biopsy proven celiac disease. The prevalence of celiac disease is 5.5% in our cohort of children and adolescents with type 1 diabetes mellitus. CONCLUSIONS The prevalence of celiac disease in Omani children and adolescents with type 1 diabetes mellitus is similar to the Worlds reported prevalence, but is less than that reported for Middle Eastern Arab children. To our knowledge, this is the first reported study on the prevalence of celiac disease in Omani children with type 1 diabetes mellitus.

Choledochal cysts in Omani children: A case series

BACKGROUND AND STUDY AIMS Choledochal cysts (CCs) are rare congenital anomalies of the biliary tract with a low incidence in the western countries and a higher incidence in the eastern part of the world. CCs have female to male preponderance. CCs type distribution is known in certain parts of the world but very little is published about the common types of CCs and gender distribution in the Arab countries. We aim to describe the CC types and gender distribution in Omani children in one centre. PATIENTS AND METHODS A retrospective review of all children diagnosed to have choledochal cysts over a 2 year period at a tertiary hospital in Oman. RESULTS We diagnosed six children with CCs. The type distribution of CCs and gender preponderance in Omani children are not similar to what is described internationally. Type IV A was the most common type (50%) and less of type I (16.7%), unlike worldwide distribution. Female to male preponderance described in the literature is not seen in our case series. Fifty percent of our patients were boys. In this case series, we compare our results to the described case reports of CCs from Arab countries and Africa and bring up the difference. CONCLUSIONS We demonstrate the unusual types of CCs and gender distribution in Omani children compared to the literature. To our best knowledge, this is the first case series of CCs in Omani children and the largest reported study in the literature in the Arab countries so far.

Novel Mutation in Wolcott–Rallison Syndrome with Variable Expression in Two Omani Siblings

Wolcott-Rallison syndrome (WRS) is an autosomal recessive disease, characterized by neonatal or early-onset non-autoimmune insulin-dependent diabetes. WRS, although rare, is recognized to be the most frequent cause of neonatal-onset diabetes. The majority of reported patients are from consanguineous families. Several mutations with variable expression of the syndrome are reported. Here we describe a six-year-old boy with WRS who was evaluated at Sultan Qaboos University Hospital and was found to have a novel homozygous nonsense mutation in the EIF2AK3 gene. His younger sister also had WRS but with milder expression. The mutation exhibited different clinical characteristics in the siblings proving that WRS patients phenotypic variability correlates poorly to genotype. This is the first case report of two Omani children with WRS and a report of a novel mutation.

Helicobacter Pylori infection in Omani children

Helicobacter pylori (H. pylori) infection is the most common chronic bacterial infection in humans. Its prevalence in Omani adults and children is not known.

Characteristics of hepatitis B infection in a sample of omani patients.

OBJECTIVES This study aimed to describe the demographic and virological characteristics of chronic hepatitis B virus (HBV) infection in a sample of Omani patients, and indirectly assess the efficacy of hepatitis B vaccination programmes and catch-up strategies. METHODS A retrospective study was undertaken of all patients with chronic HBV infections evaluated and followed-up at the Hepatology Clinic of the Armed Forces Hospital (AFH), Muscat, Oman, between January 2009 and April 2011. RESULTS A total of 154 patients met the inclusion criteria. The mean age of infected patients was 33 years with 72.7% being over 27 years. Females constituted 47.7% of the patients. Half of the cohort was referred either from the AFHs Obstetric Clinic (29.2%) or its Blood Bank (22.1%). A family history of chronic HBV infection was present in 70% of patients. A total of 95% had positive hepatitis B surface antigens, while only 5% had isolated total hepatitis B core antibodies. Most patients (96%) were hepatitis B e-antigen-negative. The majority (77.9%) had low HBV dioribonucleic acid levels of <2,000 IU/ml. Radiological features of liver cirrhosis were observed in 5%. Patients requiring treatment were in the minority (9%). CONCLUSION Almost 50% of the infected patients were female, the majority being of childbearing age. Medical authorities in Oman should consider enforcing a screening policy for all pregnant women using complete hepatitis B serological testing.

Diagnosis of Microvillous Inclusion Disease: A Case Report and Literature Review with Significance for Oman

Microvillous Inclusion Disease (MVID) is one of the congenital diarrheal disorders (CDD) caused by genetic defects in enterocyte differentiation and polarization. Its prevalence is higher in countries with a high degree of consanguinity. It causes severe, intractable secretory diarrhea leading to permanent and definitive intestinal failure with resultant dependency on parenteral nutrition (PN). Small bowel transplantation is the only curative treatment. The gold standard for diagnosis are the typical morphological abnormalities in small bowel biopsies on light and electron microscopy (EM). In recent times, histochemistry and immunohistochemistry have shown sufficient diagnostic accuracy replacing EM if the facility is unavailable or EM findings are inconclusive. We describe a neonate with CDD who was diagnosed to have MVID on the duodenal biopsy by morphohistochemical and immunophenotypic methods used for the first time in Oman. By utilizing such easy and accessible diagnostic methods, a rare genetic disorder could be diagnosed with certainty and the family could be counseled accordingly. With a high degree of consanguinity in the region, the prevalence of MVID in Oman needs to be identified once these patients are diagnosed by utilizing appropriate investigations. Care of such patients necessitates improving current parenteral nutrition services and addressing the future need for small bowel transplantation (SBTx), in Oman.