BCL11A Polymorphism in Egyptian Children with ß-Thalassemia: Relation to Phenotypic Heterogeneity.

Fetal hemoglobin (HbF) is a potent genetic modifier of ß-thalassemia phenotype. B-cell lymphoma 11A ( BCL11A ) gene results in significant silencing of HbF. The aim of this study was to assess the prevalence of different BCL11A genotypes among a cohort of Egyptian children with ß-thalassemia and to correlate them to HbF and clinical severity score. Eighty-two children with ß-thalassemia (aged 12.95 ± 3.63 years) were recruited from the Pediatric Hematology Clinic, Ain Shams University. They were divided based on the clinical severity of ß-thalassemia into three subgroups: 20 mild (24.4%), 24 moderate (29.3%), and 38 severe (46.3%). Age, gender, age of diagnosis, initial HbF level, transfusion history, and history of splenectomy were assessed. Anthropometric measures, signs of anemia and hemosiderosis, and the severity score were determined. Laboratory investigations such as complete blood picture, ferritin, and single gene polymorphism genotyping of the rs11886868 were also performed. Our findings showed that 16 children had CC genotype (19.5%), 38 had TC genotype (46.3%), and 28 had TT genotype (34.1%) of the rs#. ß-thalassemia children with TT genotype had significantly higher severity scoring than the other two groups ( p < 0.001). Moreover, mean initial HbF was found to be lower in children with TT genotype followed by TC and CC genotypes ( p < 0.001). Increased γ-globin expression associated with BCL11A gene polymorphism is associated with better clinical severity of ß-thalassemia.

Circulating spexins in children with obesity: relation to cardiometabolic risk.

BACKGROUND/OBJECTIVES: The role of spexin (SPX) in energy metabolism, endocrinal homeostasis, and vasculopathy is emerging. However, scarce data are available about its role in childhood obesity and obesity-related vasculopathy. Hence, we aimed to assess the level of SPX in obese and normal-weight children, and to correlate it with aortic distensibility (AD) and aortic stiffness index (ASI). SUBJECTS/METHODS: Forty obese children were compared to 40 matched normal-weighed children. Weight, height, and body mass index (BMI) z score and mean blood pressure (Bl-Pr) percentile on three different occasions were obtained. SPX, fasting triglycerides, cholesterol, low-density (LDL), high-density lipoproteins (HDL), and insulin were measured with calculation of the homeostatic model assessment insulin resistance (HOMA-IR). Internal aortic diameter was measured with calculation of AD, strain (AS), and ASI. RESULTS: Children with obesity had significantly lower SPX (P = 0.004), HDL (P < 0.001), and AD (P < 0.001) and higher systolic Bl-Pr (P < 0.001), diastolic Bl-Pr (P < 0.001), LDL (P = 0.011), HOMA-IR (P < 0.001), and ASI (P < 0.001). Significant negative correlation was found between SPX and BMI z score (r = -0.646, P < 0.001), systolic Bl-Pr (r = -0.641, P < 0.001), diastolic Bl-Pr (r = -0.427, P < 0.001), HOMA-IR (r = -0.349, P = 0.028), and ASI (r = -0.389, P = 0.013), while significant positive correlation was found between SPX and AS (P < 0.001, r = 0.633) and AD (P < 0.001, r = 0.612). However, no significant correlation was found between SPX and age (r = -0.01, P = 0.953), TG (r = 0.048, P = 0.767), total cholesterol (r = -0.023, P = 0.887), LDL (r = -0.299, P = 0.061), and HDL (r = 0.193, P = 0.232). CONCLUSIONS: Children with obesity had significantly lower SPX than controls. SPX was correlated with BMI, Bl-Pr, HOMA-IR, and vasculopathy in children with obesity independent of their age and lipid profile. Further studies should explore the pathomechanism of SPX and its potential role in the management of obesity and obesity-related cardiometabolic risk.

Disturbed sleep quality and architecture in adolescents with type 1 diabetes mellitus: Relation to glycemic control, vascular complications and insulin sensitivity.

BACKGROUND: Insufficient sleep duration and poor sleep quality have been linked to insulin resistance and impaired glucose metabolism. However, the relation between sleep disruption and type1 diabetes (T1D) hasn't been thoroughly explored. AIM: To study the association between sleep parameters and glycemic control, insulin resistance and micro-vascular complications among adolescent with T1D. METHODOLOGY: Sixty adolescents with T1D were compared to 60 matched controls. Diabetes-duration, insulin-therapy, fundus, Epworth Sleepiness Scale-Child Adolescent and the neuropathy disability score were assessed. Fasting lipids, fraction-C of glycosylated hemoglobin(HbA1c) and urinary albumin-excretion were measured with calculation of the insulin sensitivity score(ISS). Overnight polysomnography(PSG) was done. RESULTS: Adolescents with T1D had significantly lower sleep efficiency and rapid eye movement(REM) sleep than controls with significantly higher sleep onset latency, non-REM sleep and arousal index(P < 0.001). Although ISS was negatively correlated to total sleep time(P = 0.002); it was positively correlated to sleep efficiency(P < 0.001). HbA1C was negatively correlated to sleep efficiency(<0.001) and REM sleep(P = 0.003) and positively correlated to sleep onset latency(P = 0.005). T1D adolescents with micro-vascular complications had significantly lower sleep efficiency and REM sleep than those without micro-vascular complications. CONCLUSION: Poor sleep quality and architecture among adolescents with T1D are associated with impaired glycemic control, insulin resistance and micro-vascular complications.

Relationship of glycaemic derangement using continuous glucose monitoring system with sleep pattern among children with type 1 diabetes.

BACKGROUND: Glycaemic derangement has been linked to sleep disruption. However, the impact of glycaemic derangement on sleep pattern among children with type 1 diabetes (C-T1D) remains unraveled. AIM: To assess the effect of nocturnal hyperglycaemia and clinically significant (CS) hypoglycaemia on sleep pattern among C-T1D. METHODOLOGY: Thirty C-T1D were compared to 30 age and sex matched healthy siblings. Patients having other organ disease that might cause sleep disorders or on medications causing sleep disturbance were excluded. History included diabetes-duration, type and dose of insulin therapy, chronic diabetic-complications, and manifestations of sleep disorders. Epworth Sleepiness Scale-Child Adolescent was used. Continuous glucose monitoring system (CGMS) and overnight polysomnography were done and analysed. RESULTS: C-T1D had significantly lower sleep efficiency and significantly higher arousal index (AI), periodic limb movement index and apnoea-hypopnoea index compared to controls. Moreover, they had significantly longer sleep-onset latency, light sleep percentage, and shorter rapid eye movement percentage than controls. According to nocturnal CGMS readings, 15 C-T1D had nocturnal hyperglycaemia (50%), six experienced CS hypoglycaemia (20%), two had level-1 hypoglycaemia (6.7%), and seven were within the normoglycaemic range (23.3%). C-T1D experiencing nocturnal CS hypoglycaemia had significantly higher stage 3 sleep (P = 0.004) than controls. On the other hand, C- T1D experiencing nocturnal hyperglycaemia had significantly higher sleep onset latency (P = 0.013), light sleep percentage (P < 0.001), and AI (P < 0.001) than controls. Nocturnal CS hypoglycaemia was positively correlated to deep sleep duration, while hyperglycaemia was correlated to number of awakenings, sleep-onset latency, and light sleep duration. CONCLUSION: In children with T1D CS hypoglycaemia is associated with sleep deepening, while hyperglycaemia is associated with increased light sleep, sleep onset latency.

Serum progranulin levels in paediatric patients with Gaucher disease; relation to disease severity and liver stiffness by transient elastography.

BACKGROUND: Non-invasive screening for liver fibrosis using transient elastography (TE) could be of value in the management of Gaucher disease (GD). Progranulin (PGRN) is a novel disease modifier in GD and an independent marker of liver fibrosis. OBJECTIVES: We determined PGRN levels in paediatric patients with GD and assessed its role as a potential marker for disease severity and relation to liver stiffness by TE. METHODS: Fifty-one GD patients (20 had type 1 and 31 had type 3) with a median age of 9.5 years were compared to 40 age- and sex-matched healthy controls and were studied focusing on visceral manifestations, neurological disease, haematological profile and PGRN levels as well as abdominal ultrasound and TE. Patients were on enzyme replacement therapy (ERT) for various durations and those with viral hepatitis infection were excluded. RESULTS: By TE, 14 GD patients (27.5%) had elevated liver stiffness ≥7.0 kPa. Liver stiffness was significantly higher in type 1 GD patients than type 3 (P = .002), in splenectomized patients (P = .012) and those with dysphagia (P < .001). Liver stiffness was positively correlated with age of onset of ERT (P < .001). PGRN levels were significantly lower in GD patients compared with controls (P < .001). PGRN was significantly lower in GD patients with squint (P = .025), dysphagia (P = .036) and elevated liver stiffness (P = .015). PGRN was positively correlated with white blood cell count (r = .455, P = .002) and haemoglobin (r = .546, P < .001), while negatively correlated with severity score index (r = -.529, P < .001), liver volume (r = -.298, P = .034) and liver stiffness (r = -.652, P < .001). CONCLUSIONS: Serum PGRN levels were associated with clinical disease severity and elevated liver stiffness in paediatric GD patients.

Evaluation of continuous glucose monitoring system for detection of alterations in glucose homeostasis in pediatric patients with ß-thalassemia major.

BACKGROUND: Disturbances of glucose metabolism are common in ß-thalassemia major (ß-TM). AIM: This study was conducted to assess the pattern of glucose homeostasis in pediatric ß-TM patients comparing oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS). METHODS: Two-hundred ß-TM patients were studied and those with random blood glucose (RBG) ≥7.8 mmol/L (140 mg/dL) were subjected to OGTT, insertion of CGMS and measurement of fasting C peptide, fasting insulin, and hemoglobin A1c (HbA1c). RESULTS: Twenty patients (10%) had RBG ≥ 7.8 mmol/L. Using OGTT, 6 out of 20 patients (30%) had impaired glucose tolerance (IGT) while 7 (35%) patients were in the diabetic range. CGMS showed that 7/20 (35%) patients had IGT and 13 (65%) patients had diabetes mellitus (DM); 10 of the latter group had HbA1c readings within diabetic range. The percentage of diabetic patients diagnosed by CGMS was significantly higher than that with OGTT (P = 0.012). Serum ferritin was the only independent variable related to elevated RBG. All ß-TM patients with DM were non-compliant to chelation therapy. CONCLUSIONS: The use of CGMS in the diagnosis of early glycemic abnormalities among pediatric patients with ß-TM appears to be superior to other known diagnostic modalities.