Is HLA-DQ typing useful in screening for celiac disease among Arabs with type 1 diabetes? A case-control study.

OBJECTIVES: The data on the usefulness of DQ-typing in screening for celiac disease (CD) among type 1 diabetic (T1D) patients came from the West. We conducted this study among T1D patients to: (1) determine the frequency of DQ-genotypes, (2) assess the risk associated with human leukocyte antigen (HLA)-DQ genotypes, and (3) identify the cost-effective screening strategy. METHODS: HLA-DQ genotyping was performed on 67 T1D patients with CD (cases) (mean age 15 years) and 224 T1D patients without CD (controls) (mean age 18.29 years) (2021-2023). The entry criterion for the control group was duration of T1D ≥5 years and negative annual celiac serology assay. RESULTS: On comparison of the cases versus controls, T1D patients carrying homozygous DQ2.5 genotype (30% vs. 13.8%) or DR3-DQ2.5 haplotype (81.3% vs. 65.7%) showed significantly "higher risk" (odds ratio [OR] = 2.64, p = 0.002; OR = 2.3, p = 0.008, respectively) to develop CD. Only 4% do not harbor any of the CD-at risk genotypes (DQ2.5, DQ8, or DQ2.2) and none developed CD. Heterozygous DQ8 was associated with a significantly lower risk of developing CD with OR of 0.123 (1.5% in cases vs. 10.3% in controls, p = 0.022). CONCLUSION: Only 4% of Saudi patients with T1D carry DQ-genotypes at no risk to develop CD, which supports the European guidelines that recommend celiac serology test as the most cost-effective screening method. We identified the risk gradient associated with DQ-genotypes to develop CD in our population which could help in counseling patients for the risk to develop CD and planning follow-up serology tests.

Sickle Cell Disease is Associated With Elevated Levels of Skin Advanced Glycation Endproducts.

Sickle cell disease (SCD) is associated with increased oxidative stress which potentially enhances generation of advanced glycation endproducts (AGEs). We estimated skin accumulation of AGEs in SCD patients and assessed their relationship with hemolysis and nephropathy. Skin intrinsic fluorescence (SIF), an estimate of AGEs, was assessed in African American patients with and without SCD. After skin excitation with light at 375, 405, and 420 nm, raw autofluorescence was adjusted using specific intrinsic corrections. Group differences in SIF were evaluated by multiple variable regression using chronological age and sex as covariates. The relationship of SIF with reticulocyte count, serum lactate dehydrogenase, estimated glomerular filtration rate (GFR), plasma creatinine, bilirubin, and urine microalbumin was assessed. There were 48 SCD patients (29 male/19 female, age=13.4±3.6 y) and 51 controls (25 male/26 female, age=10.4±5.0 y). SIF375(1.0,0.0), SIF405(0.5,0.5), and SIF420(0.5,0.5) were significantly higher in SCD patients. There was no difference in SIF between SCD patients with and without microalbuminuria. SIF 420(0.5,0.5) was correlated with reticulocyte count (r=0.33; P=0.03). Skin AGEs as estimated by SIF were higher in children with SCD and weakly associated with 1 measure of hemolysis. Further study is needed to determine whether chronic increased deposition of AGEs is associated with development of complications of SCD.

Predicting age at onset of type 1 diabetes in children using regression, artificial neural network and Random Forest: A case study in Saudi Arabia.

The rising incidence of type 1 diabetes (T1D) among children is an increasing concern globally. A reliable estimate of the age at onset of T1D in children would facilitate intervention plans for medical practitioners to reduce the problems with delayed diagnosis of T1D. This paper has utilised Multiple Linear Regression (MLR), Artificial Neural Network (ANN) and Random Forest (RF) to model and predict the age at onset of T1D in children in Saudi Arabia (S.A.) which is ranked as the 7th for the highest number of T1D and 5th in the world for the incidence rate of T1D. De-identified data between (2010-2020) from three cities in S.A. were used to model and predict the age at onset of T1D. The best subset model selection criteria, coefficient of determination, and diagnostic tests were deployed to select the most significant variables. The efficacy of models for predicting the age at onset was assessed using multi-prediction accuracy measures. The average age at onset of T1D is 6.2 years and the most common age group for onset is (5-9) years. Most of the children in the sample (68%) are from urban areas of S.A., 75% were delivered after a full term pregnancy length and 31% were delivered through a cesarean section. The models of best fit were the MLR and RF models with R2 = (0.85 and 0.95), the root mean square error = (0.25 and 0.15) and mean absolute error = (0.19 and 0.11) respectively for logarithm of age at onset. This study for the first time has utilised MLR, ANN and RF models to predict the age at onset of T1D in children in S.A. These models can effectively aid health care providers to monitor and create intervention strategies to reduce the impact of T1D in children in S.A.

Screening for testicular adrenal rest tumors among children with congenital adrenal hyperplasia at King Fahad Medical City, Saudi Arabia.

OBJECTIVES: To assess the incidence of testicular adrenal rest tumors (TARTs) among male children with congenital adrenal hyperplasia (CAH) in tertiary care centers. METHODS: All male children aged 1-14 years diagnosed with CAH due to 21-hydroxylase deficiency (21 HOD), 11ß-hydroxylase deficiency, and 3ß-hydroxysteroid dehydrogenase deficiency, confirmed by biochemical and/or genetic testing, underwent scrotal ultrasound examination to identify TARTs. After receiving the diagnosed patients' data, patients' electronic medical records were accessed to collect demographic data and scrotal ultrasound results, along with growth parameters and specific biochemical test results within 2 months of the ultrasound. RESULTS: TARTs were observed in 5 (10.9%) of 46 male children with CAH. Four patients with positive findings had 21 HOD classical CAH with salt loss and one had 21 HOD simple virilizing classical CAH. All patients had poor compliance and stage 2 bilateral TARTs. Three TART-positive patients (60.0%) had high ACTH levels, 5 patients (100%) had elevated 17-OHP levels, and 5 patients (100%) had advanced bone age. The youngest patient with positive findings was 4 years old. CONCLUSIONS: The prevalence of TARTs increases with age and can be present in young males with classical CAH with 21 HOD. It is associated with elevated 17-hydroxyprogesterone (17-OHP) and advanced bone age SDS. TARTs are less likely to be associated with nonclassical CAH with 21 HOD or other less common CAHs due to 11ß-hydroxylase deficiencies and 3ß-hydroxysteroid dehydrogenase deficiencies in children. Our study recommends early and routine screening of TARTs in children with CAH.

Adipsic Diabetes Insipidus in Children: A Case Report and Practical Guide.

BACKGROUND Diabetes insipidus (DI) is a clinical syndrome characterized by polyuria and polydipsia that result from a deficiency of antidiuretic hormone (ADH), central DI, or resistance to ADH, nephrogenic DI. In otherwise healthy patients with DI, normal thirst mechanism, and free access to water, the thirst system can maintain plasma osmolality in the near-normal range. However, in cases where DI presents with adipsia, cognitive impairment, or restricted access to water, true hypernatremia may occur, leading to severe morbidity and mortality. CASE REPORT We report a case of a 2-year-old boy who had global developmental delay and post-brain debulking surgery involving the hypothalamic region, which resulted in central DI and thirst center dysfunction. We describe the clinical presentation, the current understanding of adipsic DI, and a new practical approach for management. The main guidelines of treatment include (1) fixed desmopressin dosing that allows minimal urinary breakthroughs in-between the doses; (2) timely diaper weight-based replacement of water; (3) bodyweight-based fluid correction 2 times a day, and (4) providing the nutritional and water requirements in a way similar to any healthy child but at fixed time intervals. CONCLUSIONS This plan of management showed good effectiveness in controlling plasma sodium level and volume status of a child with adipsic DI without interfering with his average growth. This home treatment method is practical and readily available, provided that the family remains very adherent.

The Impact of COVID-19 Pandemic Lockdown on the Incidence of New-Onset Type 1 Diabetes and Ketoacidosis Among Saudi Children.

Background: Overburdened healthcare systems during the coronavirus disease (COVID-19) pandemic led to suboptimal chronic disease management, including that of pediatric type 1 diabetes mellitus (T1DM). The pandemic also caused delayed detection of new-onset diabetes in children; this increased the risk and severity of diabetic ketoacidosis (DKA). We therefore investigated the frequency of new-onset pediatric T1DM and DKA in Saudi Arabia during the COVID-19 pandemic and compared it to the same period in 2019. Methods: We conducted a multicenter retrospective cohort study, including patients aged 1-14 years admitted with new-onset T1DM or DKA during the COVID-19 pandemic (March-June 2020) and the same period in 2019. We assessed factors including age, sex, anthropometric measures, nationality, duration of diabetes, diabetes management, HbA1c levels, glycemic control, cause of admission, blood gas levels, etiology of DKA, DKA complications, length of hospital stay, and COVID-19 test status. Result: During the lockdown, 106 children, compared with 154 in 2019, were admitted to 6 pediatric diabetes centers. Among the admissions, DKA was higher in 2020 than in 2019 (83% vs. 73%; P=0.05; risk ratio=1.15; 95% confidence interval, 1.04-1.26), after adjusting for age and sex. DKA frequency among new-onset T1DM and HbA1c levels at diagnosis were higher in 2020 than in 2019 (26% vs. 13.4% [P=<0.001] and 12.1 ± 0.2 vs. 10.8 ± 0.25 [P<0.001], respectively). Females and older patients had a higher risk of DKA. Conclusion: The lockdown implemented in Saudi Arabia has significantly impacted children with T1DM and led to an increased DKA frequency, including children with new-onset T1DM, potentially owing to delayed presentation.

Mean glycosylated hemoglobin in children with type 1 diabetes at King Fahad Medical City, Riyadh, Saudi Arabia.

BACKGROUND: Type 1 diabetes is the third most common chronic disease among teenagers. In Saudi Arabia, there is a gap of knowledge regarding hemoglobin A1C (HbA1c) concentration levels, and adherence to regular follow-up visits by patients. The aim of this study was to determine the mean glycosylated hemoglobin (HbA1c) levels in diabetic children who have been diagnosed with type 1 diabetes and were being followed up at a tertiary care center in Saudi Arabia. MATERIALS AND METHODS: This cross-sectional study was conducted among all diabetic children treated at King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia. Data were retrieved and analysed during the period from September to December 2018. Diabetic patients of <18 years and who were being followed up at KFMC were included in the study. Data on age, sex, duration of illness, associated comorbidities, antidiabetic regimen, and HbA1c levels were obtained. Student t-test was used to compare quantitative parameters between two groups, and Chi-square employed to test for associations between categorical variables at 5% significance level. RESULTS: A total of 510 patients of were included in the study; about 53% were females. The mean HbA1c level was 10.6% and females showed higher HbA1c levels. Data showed a strong correlation between age and HbA1c levels (P < 0.001), with older patients showing higher HbA1c levels. The HbA1c levels also increased as the duration of disease increased. The median number of patient visits to KFMC was two per year. No statistically significant differences were observeed for type of treatment for diabetes. Celiac disease, the most frequent comorbidity, was seen in 50% of patients. CONCLUSION: Diabetic children who were followed up at KFMC had high HbA1C level (10.6%), and lower than recommended follow-up visits per year. The treating physicians should educate patients and their legal guardians on the importance of follow-up visits and their role in controlling HbA1C levels, and following healthier lifestyle.

A Rare Case of Painful Goiter Secondary to Pediatric Hashimoto's Thyroiditis Requiring Thyroidectomy for Pain Control.

Hashimoto's thyroiditis (HT) usually presents as painless thyroid swelling. Painful pediatric HT is a rare condition with limited literature on pain management. We report a 15-year-old female who presented with 4 weeks history of fatigue, malaise and progressive, painful midline thyroid swelling. There was no difficulty in swallowing, no fever or recent upper respiratory infection symptoms. Exam was remarkable for diffusely enlarged, very tender, and non-nodular thyroid. Thyroid function tests, C-reactive protein, and complete blood count were normal. Ultrasound revealed diffusely enlarged non-nodular, non-cystic gland with mild increased vascularity. Diagnosis of HT was confirmed by biopsy and thyroid antibodies. Over a 6 week period, pain management with ibuprofen, levothyroxine, corticosteroid, gabapentin and amitriptyline was unsuccessful. Ultimately, total thyroidectomy resulted in complete resolution of thyroid pain. We can conclude that thyroidectomy may be considered for the rare case of painful HT in children.