Loss of helicase C-terminal domain of SMARCAL1 protein associated with severe Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia (SIOD) is a rare multi-system condition caused by biallelic loss-of-function mutations in the SMARCAL1 gene. This disorder is characterized by disproportionate growth failure, T-cell deficiency, and renal dysfunction. Pathogenic variants in the SMARCAL1 gene have been reported in only approximately half of SIOD-affected individuals. Among these alterations, nonsense and frameshift mutations generally lead to a severe phenotype with early onset. In this study, we identified novel mutations in an Iranian patient with SIOD. A 4-year-old girl with developmental delay and facial dysmorphism was referred to our center for molecular diagnosis. We applied whole-exome and Sanger sequencing for co-segregation analysis. Subsequently, bioinformatic analysis was performed to assess the pathogenic effects of the variants and their post-transcriptional effects. We discovered two novel mutations (c.2281delT and c.2283delA) in exon 15 of the SMARCAL1 gene, resulting in a truncated protein with a loss of 193 amino acids (p.S761Rfs*1). Variant effect predictors indicated that these variants are pathogenic, and multi-sequence alignments revealed high conservation of this region among different species. Given that our patient exhibited severe a phenotype and passed away soon after receiving a definitive molecular diagnosis, we propose that the loss of the helicase C-terminal domain in the deleted part of SMARCAL1 may lead to the severe form of SIOD. Besides, the combination of growth retardation and bone abnormalities also plays a crucial role in the early diagnosis of the disease.

Topical tranexamic acid as a novel treatment for bleeding peptic ulcer: A randomised controlled trial.

BACKGROUND: Peptic ulcers are among the most common causes of upper gastrointestinal (GI) bleeding in children. The standard care for GI bleeding is endoscopy for diagnostic and therapeutic purposes. We aimed to assess the effect of topical tranexamic acid (TXA) via endoscopic procedures in children with GI bleeding caused by bleeding ulcers. PROCEDURE: In this randomised controlled trial, 120 children were evaluated by diagnostic procedures for GI bleeding, of which 63 (30 girls, 33 boys) aged 1-month to 15 years were recruited. The patients were randomly divided into case and control groups. In the case group, TXA was administered directly under endoscopic therapy. In the control group, epinephrine (1/10,000) was submucosally injected to the four quadrants of ulcer margins as the routine endoscopic therapy. In both groups, the patients received supportive medical therapy with intravenous fluids and proton pump inhibitor drugs. RESULTS: The mean ± standard deviation age of the children was 5 ± 2.03 years. Rebleeding occurred in 15 (11.4%) and 21 (9.8%) patients in the case and control groups, respectively (P = 0.50). The frequency of blood transfusion episodes (P = 0.06) and duration of hospital stay (P = 0.07) were not statistically different between the groups. CONCLUSION: Using topical TXA via endoscopic procedures may be effective in cases of GI bleedings caused by active bleeding ulcers. In order to establish this therapeutic effect, a large number of clinical studies are needed.

Electrophysiologic pattern and prevalence of subclinical peripheral neuropathy in children and adolescents with type I diabetes mellitus in Iran.

OBJECTIVES: To evaluate electrophysiologic pattern of subclinical diabetic peripheral neuropathy (DPN) in children and adolescents with type 1 diabetes mellitus (T1DM) based on nerve conduction study. METHODS: In this cross sectional study, 40 children and adolescents (62.5% female with mean age of 12.73 ± 0.43 years) with T1DM for at least 5 years attending the Pediatrics Clinics. Tabriz University of Medical Sciences, Tabriz, Iran, between 2014 and 2015 were recruited. Demographic and laboratory findings were recorded and all patients underwent clinical neurological examination and electrophysiologic studies. RESULTS: According to electrophysiologic studies, DPN was found in 57.5% of patients including early stage of neuropathy (15%), mild sensory axonal neuropathy (25%), mild sensory motor axonal neuropathy (10%), and moderate sensory motor axonal neuropathy (7.5%). Age, duration of diabetes, fasting blood sugar, and glycosylated hemoglobin levels had no significant difference between patients with and without DPN. Reduced deep tendon reflexes were observed in the upper limb (30%) and lower limb (47.5%) of patients, which were both significantly higher in DPN patients (upper limb [p=0.03] and lower limb [p=0.04]). The most frequent electrophysiologic findings were unobtainable H-reflex, low amplitude sural, and median sensory responses. CONCLUSION: Subclinical DPN is a common complication found in children and adolescents with TIDM and peripheral sensory axonal neuropathy is the most frequent type. Nerve conduction study is recommended for early detection of DPN and prevention of its progress.

Effect of insulin therapy on IGF-1 level in children with new-onset type 1 diabetes mellitus: a comparison between DKA and non-DKA.

BACKGROUND AND OBJECTIVE: The issue of insulin-like growth factor 1 (IGF-1) and diabetes in adults and type 2 diabetes has been well investigated. A few studies have investigated the serum IGF-1 level at the onset of type 1 diabetes mellitus (T1DM) in children. In the present study, we investigated the IGF-1 level of T1DM children before and after insulin therapy. SUBJECTS AND METHODS: Between August 2011 and October 2012, 62 children with newly diagnosed T1DM were recruited. Serum IGF-1 levels were compared before and 1 month after insulin therapy between diabetic ketoacidosis (DKA) and non-DKA patients. RESULTS: Thirty-one patients without DKA (18 girls and 13 boys, mean age 8.8 ± 3.01 years) and 31 patients with DKA (18 girls and 13 boys, mean age 8.3 ± 3.7 years) were studied. The mean IGF-1 in the DKA group was lower than that in the non-DKA group; however, this difference was not statistically significant (p=0.10). Serum IGF-1 levels increased significantly 1 month after insulin therapy in both the DKA (p<0.001) and non-DKA (p<0.001) groups. CONCLUSION: Serum IGF-1 level is reduced in new-onset T1DM children. A significant increase in serum IGF-1 level can occur with insulin therapy in both DKA and non-DKA children.

Comparison of vitamin D deficiency and secondary hyperparathyroidism in obese and non-obese children and adolescents.

Obesity subjects individuals into metabolic and endocrine disorders. Thus obesity may increase the risk of vitamin D deficiency. This text aims at studying the prevalence of vitamin D deficiency and secondary hyperparathyroidism in obese children. In a non-randomized case control study on 52 obese children (body mass index (BMI) >95th percentile) aged 4 to 16 years undertaken at the outpatient endocrine clinic of the Children Hospital at Tabriz University between 2009-2011. This study was conducted to compare the prevalence of vitamin D deficiency and secondary hyperparathyroidism in obese children compared with 57 non obese (BMI < 85th percentile). 109 children including 52 (50.5%) boys and 57 (49.5%) girls were studied. Most of case (76.9%) and control (42.1%) groups suffered from degrees of vitamin D deficiency. There was meaningful statistical difference between two groups considering to vitamin D deficiency and parathyroid hormone (p = 0.001). A negative relations was found between iPTH and vit D level (p < 0.001, r = -0.2), BMI and 25-OH vit D (p < 0.001, r = -0.2). A positive relation was observed between parathyroid hormone and BMI (p = 0.009, r = 0.1). Obese children are at high risk at vitamin D deficiency and secondary hyperparathyroidism. BMI appears to be an important risk factor for vitamin D deficiency.

Prevalence of impaired glucose tolerance and insulin resistance among obese children and adolescents.

PURPOSE: Obesity is one of the most important nutritional disorders in the world which has an obvious relationship with the incidence of metabolic diseases. Obesity prevalence has increased among children and adolescents during recent decades, leading to a rise in Type 2 diabetes mellitus (DM II) prevalence in these two age brackets. Hence, the aim of this study was to assess impaired glucose tolerance and insulin resistance, and gather metabolic findings in obese children and adolescents. METHODS AND MATERIALS: We studied 110 obese children and adolescents (body mass index > 95th percentile for age and gender) 4-18 years of age referred to the endocrine clinic of the Children's Hospital at Tabriz University in a descriptive cross-sectional study. Fasting glucose, insulin, and lipid profile in all subjects were determined. Oral glucose tolerance test after eating 75 g/kg glucose was performed. Homeostatic model assessment was used to estimate insulin resistance. RESULTS: Impaired glucose tolerance and insulin resistance prevalence in 68 obese adolescents was 14.7% and 31.8%, respectively. Impaired glucose tolerance and insulin resistance was not seen in 23.8% of 42 obese children. No case of DM II was seen. There was a significant statistical difference in glucose (P = 0.003) and insulin (P < 0.001) level at minute 120 in individuals with impaired glucose tolerance compared to obese children and adolescents without impaired glucose tolerance. Rate of insulin resistance in patients with impaired glucose tolerance was greater and had a significant statistical difference (P = 0.03). CONCLUSION: Obesity has a close relationship with increased risk of impaired glucose tolerance and insulin resistance in children and adolescents. Oral glucose tolerance test, unlike fasting glucose test, is a benefit test to predict impaired glucose tolerance. With prompt identification and treatment of obese children with impaired glucose tolerance, we can prevent it from progression towards DM II.