Background & Aims Proprotein convertase 1/3 (PC1/3) deficiency, an autosomal recessive disorder caused by rare mutations in the PCSK1 gene, has been associated with obesity, severe malabsorptive diarrhea, and certain endocrine abnormalities. Common variants in PCSK1 have also been associated with obesity in heterozygotes in several population studies. PC1/3 is an endoprotease that processes many prohormones expressed in endocrine and neuronal cells. We investigated clinical and molecular features of PC1/3 deficiency. Methods We studied the clinical features of 13 children with PC1/3 deficiency and performed sequence analysis of PCSK1. We measured enzymatic activity of recombinant PC1/3 proteins. Results We identified a pattern of endocrinopathies that develop in an age-dependent manner. Eight of the mutations had severe biochemical consequences in vitro. Neonates had severe malabsorptive diarrhea and failure to thrive, required prolonged parenteral nutrition support, and had high mortality. Additional endocrine abnormalities developed as the disease progressed, including diabetes insipidus, growth hormone deficiency, primary hypogonadism, adrenal insufficiency, and hypothyroidism. We identified growth hormone deficiency, central diabetes insipidus, and male hypogonadism as new features of PCSK1 insufficiency. Interestingly, despite early growth abnormalities, moderate obesity, associated with severe polyphagia, generally appears. Conclusion In a study of 13 children with PC1/3 deficiency caused by disruption of PCSK1, failure of enteroendocrine cells to produce functional hormones resulted in generalized malabsorption. These findings indicate that PC1/3 is involved in processing of one or more enteric hormones that are required for nutrient absorption.

Background/Aim: To provide the most recent estimate of childhood obesity and determine the trend in childhood obesity in Riyadh city over the past two decades, by comparing our results with previous studies that published data comparable to our study in terms of geography, sample age (6–16 years), and use of World Health Organization (WHO) cut-offs to define obesity. Patients and Methods: A cross-sectional study was conducted in 2015 among school children in Riyadh city. A sample of 7930 children (67% girls) aged 6–16 years were randomly selected. Body mass index for age and gender above +1 and below +2 standard deviation scores (SDS) defined overweight (SDS, z-scores) and >+2 SD scores defined obesity. Results: The overall prevalence of overweight and obesity was 13.4% (14.2% for girls and 12% for boys; P = 0.02) and 18.2% (18% for girls and 18.4% for boys; P = 0.73), respectively. When compared with the WHO-based national prevalence rate of obesity reported in 2004 (≈9.3%), the obesity rate has doubled over a 10-year period. There was a significantly higher prevalence of obesity in adolescents (>11 years) than in children (20.2% vs 15.7%; P < 0.01). Overweight and obesity increased significantly with higher levels of socioeconomic status. Obese children were at 1.5 and 2 times risk of developing gas bloating and vomiting than non-obese children. Conclusion: The prevalence of overweight and obesity has risen alarmingly among Saudi children and adolescents over the past decade and should make a strong case to initiate and monitor effective implementation of obesity prevention measures.

liver disease or portal hypertension, hypoxemia (PaO(2) < 70 mmHg or SaO(2) < 95%) and intrapulmonary shunting documented by macroaggregated albumin scan ratio of >4% (classified mild group [<20%], moderate group [20-40%] and severe group [>40%]). Resolution of HPS post-liver transplant was defined as PaO(2) > 70 mmHg or SaO(2) > 95%. Eighteen children (six male [34%], median age at diagnosis of HPS 8.6 [1-15.5] yr) had HPS: biliary atresia (n = 8), idiopathic biliary cirrhosis (n = 4), progressive intrahepatic cholestasis (n = 2), miscellaneous (n = 4). The majority had mild shunting (n = 8). Fourteen underwent transplantation with resolution of HPS in 13. Six developed complications: hepatic artery thrombosis (n = 4), biliary (n = 2). Four children died (28%), two pretransplant. There was a tendency towards shunt fraction worsening to a slower degree over time. One-yr survival rate post-transplant was 93%. Median PaO(2) was significantly lower in non-survivors compared to survivors (43 vs. 55.2 mmHg, p = 0.03). There was correlation between oxygen parameters pretransplant and time to HPS resolution post-transplant. HPS is reversible after transplant, but is associated with increasing mortality and morbidity.

BackgroundThere is lack of data on prevalence of celiac disease (CD) in children with type 1 diabetes (T1D) in Arabs in the Middle East. The present investigation aims to study the prevalence rate and clinical characteristics of CD among Saudi children with T1D using a combination of the most sensitive and specific screening serologic tests (anti- tissue transglutaminase antibodies IgA [anti-TTG] and ednomyseal antibodies [EMA]) and to determine the lower cut-off value of anti- anti-TTG level that best predicts CD in children with T1D.MethodsChildren with T1D following in diabetic clinic have been prospectively screened for presence of CD, over a two-year period (2008–2010), by doing anti-TTG, EMA, and total IgA. Children with positive anti-TTG titres (>50 U/ml) and/or EMA and children with persistently low positive anti-TTG titres (two readings 20–50 U/ml; within 6 months intervals) had upper endoscopy and 6 duodenal biopsies.ResultsOne hundred and six children with T1D have been screened for CD: age ranged between 8 months to 15.5 years (62 females). Nineteen children had positive anti-TTG and/or EMA, however only 12 children had biopsy proven CD (11.3%). Five of 12 had gastrointestinal symptoms (42%). Children with T1D and CD had significantly lower serum iron than children with T1D alone (8.5 μgm/L Vs 12.5 μgm/L; P = 0.014). The sensitivity and specificity of anti-TTG were 91.6% and 93.6%, with a positive and negative predictive value of 64.7% and 98.8%, respectively. Receiver operated characteristics analysis for the best cut-off value of anti-TTG level for diagnosis of CD was 63 units (sensitivity 100% and specificity 98.8%).ConclusionCD is highly prevalent among Saudi children with T1D. Anti-TTG titres more than 3 times the upper limit of normal has very high sensitivity and specificity for diagnosis of CD in T1D children.

Our study provided evidence of a high prevalence of CD among Saudi children (1.5%), a rate that is at least twice the average prevalence rate in Europe and North America.