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BACKGROUND: Obesity is a complicated phenomenon which is a combination of genetic, environmental, and psychological factors. Genetic factors of obesity play an important role in individual risk. It is well known that obese children have disturbed puberty timing. To the best of our knowledge, no study has been performed to investigate the association between MC4R gene mutation and puberty timing. METHODS: This study was performed as a cross-sectional study evaluating the near MC4R rs17782313 variation in 60 obese children and 98 healthy non obese children. Weight, height, BMI ( Body Mass Index ), BMI z-score (BMIz), family history of diabetes mellitus and obesity, the age of the obesity onset, overeating behavior, type of obesity (central or general) and puberty stage were evaluated in 60 obese children. RESULTS: The average age of the participants was 14.87 (+/- 1.3) years, with average weight and BMI of 90.77 (+/-12.2) Kg and 31.72 (+/-4.35) Kg/m2, respectively. Compared to healthy non obese patients, those with C-T genotype (C-T Vs. T-T and C-C) had higher odds of obesity than those with T-T and C-C genotype (p

Background: The purpose of this study was to compare the effectiveness of once-daily versus twice-daily insulin detemir injection in children with type 1 diabetes mellitus (T1DM). Methods: In this randomized 4-month clinical trial, 60 children aged 33 - 156 months with T1DM were randomly assigned into two groups, once-daily (group 1) and twice-daily (group 2) detemir insulin injection with pre-meal insulin Aspart. The first month of the study was devoted to educating the patients and insulin dose titration. Hemoglobin A1C (HbA1C) measured at the end of the first month and again after the fourth month. Hypoglycemia as one of the major complications was defined as blood glucose lower than 70 mg/dL with clinical symptoms or blood glucose lower than 50 mg/dL in the absence of clinical symptoms. Results: Mean HbA1C in the fourth month was 8.5% ± 1% in group 1 and 8.5% ± 1.1% in group 2 (P = 0.98). Mean changes in the fourth month compared to baseline were -0.09% (95% CI: -0.47 - 0.3) in group 1, and -0.42% (95% CI: -0.94 - 0.09) in group 2 (P = 0.273). The treatment modification rate was 39% and 15% in groups 1 and 2, respectively (P = 0.02). However, there were no statistically significant differences between the two groups in terms of insulin dose, hypoglycemia, and other complications. Conclusions: Twice-daily injections did not change HbA1c in comparison with once-daily injections. However, the lower treatment modification rate in the twice-daily group in the age group of our study was considerable.

Mucopolysaccharidoses (MPSs) are rare lysosomal storage diseases, resulting from deficiencies of enzymes responsible for Glycosaminoglycans (GAGs) degradation. This leads to accumulation of GAGs in tissues and their excretion in urine, with a wide variety of manifestations. Early diagnosis of MPSs is strictly recommended due to available therapy that can slow down disease progression during the early ages. This study aimed to evaluate patients with suspected MPS referred to Children's Medical Center laboratory over eight years. We also evaluated the usefulness of urine GAG as a screening test for identification of such patients. A total of 1414 patients (40% female, 60% male, with mean age 3.1 ± 4.1years) have participated in this study. The urinary GAG analysis (uGAG) was performed by 1, 9-dimethyl-methylene blue (DMMB) and Berry spot test (BST). All patients with positive and mild positive results or with disease-related symptoms were evaluated in terms of definitive diagnosis, received treatments, morbidity, and mortality rate. In 407 (36.5%) patients uGAG were positive or mild positive, of which 26.3% suffered from one of the types of MPSs, 28.5% suffered from other diseases, 32.9% were undiagnosed, 12.3% were apparently healthy, and 19 died. The negative predictive value of uGAG test in our study was 100%. About 21% of MPSs patients received enzyme replacement therapy, while four patients underwent stem cell transplants. The rest received supportive care. We concluded that a combination of DMMB and BST methods has acceptable sensitivity for screening suspicious MPS patients.

Premature pubarche (PP) is the appearance of sexual hair in children before puberty. The PP phenotype may attribute to nonclassic congenital adrenal hyperplasia (NC-CAH). In this study, we investigated the role of CYP21A2 gene variants in patients with PP in the Iranian population. Forty patients (13 males and 27 females), clinically diagnosed with PP, were analyzed for molecular testing of CYP21A2 gene variants. Direct sequencing was performed for the samples. Also, gene dosage analysis was performed for the cases. Fourteen patients (35%) had a mutation of p.Gln318X and p.Val281Leu, out of which 10% had regulatory variants. Approximately 10% of the patients were homozygous (NC-CAH). 78.5% (11/14) of patients had trimodular RCCX of which 5 patients had two copies of CYP21A1P pseudogene. The prevalence of p.Val281Leu was higher than p.Gln318X in PP patients. In conclusion, CYP21A2 variant detection has implications in the genetic diagnosis of PP phenotype. The genetic characterization of the CYP21A2 gene is important for characterizing the variable phenotype of carriers and genetic counseling of PP and NC-CAH patients.

BackgroundType-1 diabetes (T1D) occurs following autoimmune-induced pancreatic beta cells death. Among several treatment modalities, Mesenchymal Stem Cells (MSCs) transplantation is promising for autoimmune disorders due to immunomodulation, regeneration, and migration to damaged tissue upon systemic injection. This study assessed the safety and efficacy of intravenous injection of autologous bone marrow-derived MSCs in newly diagnosed T1D patients. MethodsAfter receiving informed consent, 21 patients who met the study criteria were enrolled and randomly assigned to receive either MSCs or placebo. Each patient in the experimental group received two doses of MSCs and followed for at least one year post-transplantation. ResultsThe results have shown that this transplantation is safe and significantly reduces the number of hypoglycemic episodes. MSCs transplantation improved glycated hemoglobin (HbA1c), shifted serum cytokine patterns from pro-inflammatory to anti-inflammatory, increased the number of regulatory T-cells in the peripheral blood, and improved quality of life. Early transplantation of MSCs significantly improved HbA1c and C-peptide levels and shifted pro-inflammatory cytokines to anti-inflammatory cytokines. Also, exercise combined with MSCs transplantation improved glycemic and immunologic indices. ConclusionsIn conclusion, autologous MSC transplantation is safe and effective, and its early transplantation is a promising treatment in newly-diagnosed T1D children suffering from hypoglycemic episodes. Trial registrationThis clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the identifier IRCT ID: IRCT2016070428786N1 registered on August 20, 2016 (Retrospectively registered) (https://en.irct.ir/trial/23256) and at the U.S. National Institutes of Health (ClinicalTrials.gov) with the related identifier NCT04078308 registered on September 6, 2019 (Retrospectively registered). (https://clinicaltrials.gov/ct2/show/NCT04078308)

BackgroundType-1 diabetes (T1D) occurs following autoimmune-induced pancreatic beta cells death. Among several treatment modalities, mesenchymal stem cells (MSCs) transplantation is promising for autoimmune disorders due to immunomodulation, regeneration, and migration to damaged tissue upon systemic injection. This study assessed the safety and efficacy of intravenous injection of autologous bone marrow-derived MSCs in newly diagnosed T1D patients.MethodsAfter receiving informed consent, 21 patients who met the study criteria were enrolled and randomly assigned to receive either MSCs or placebo. Each patient in the experimental group received two doses of MSCs and was followed for at least one-year post-transplantation.ResultsThe results have shown that this transplantation is safe and significantly reduces the number of hypoglycemic episodes. MSCs transplantation improved glycated hemoglobin (HbA1c), shifted serum cytokine patterns from pro-inflammatory to anti-inflammatory, increased the number of regulatory T-cells in the peripheral blood, and improved quality of life. Early transplantation of MSCs significantly improved HbA1c and C-peptide levels and shifted pro-inflammatory cytokines to anti-inflammatory cytokines. Also, exercise combined with MSCs transplantation improved glycemic and immunologic indices.ConclusionsTaken together, autologous MSC transplantation is safe and effective, and its early transplantation is a promising treatment in newly diagnosed T1D children suffering from hypoglycemic episodes.Trial registration: This clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the identifier IRCT ID: IRCT2016070428786N1 registered on August 20, 2016 (Retrospectively registered) (https://en.irct.ir/trial/23256) and at the U.S. National Institutes of Health (ClinicalTrials.gov) with the related identifier NCT04078308 registered on September 6, 2019 (Retrospectively registered). (https://clinicaltrials.gov/ct2/show/NCT04078308).

Aim To examine the extent to which discriminatory testing using antibodies and Type 1 diabetes genetic risk score, validated in European populations, is applicable in a non‐European population. Methods We recruited 127 unrelated children with diabetes diagnosed between 9 months and 5 years from two centres in Iran. All children underwent targeted next‐generation sequencing of 35 monogenic diabetes genes. We measured three islet autoantibodies (islet antigen 2, glutamic acid decarboxylase and zinc transporter 8) and generated a Type 1 diabetes genetic risk score in all children. Results We identified six children with monogenic diabetes, including four novel mutations: homozygous mutations in WFS1 (n=3), SLC19A2 and SLC29A3, and a heterozygous mutation in GCK. All clinical features were similar in children with monogenic diabetes (n=6) and in the rest of the cohort (n=121). The Type 1 diabetes genetic risk score discriminated children with monogenic from Type 1 diabetes [area under the receiver‐operating characteristic curve 0.90 (95% CI 0.83–0.97)]. All children with monogenic diabetes were autoantibody‐negative. In children with no mutation, 59 were positive to glutamic acid decarboxylase, 39 to islet antigen 2 and 31 to zinc transporter 8. Measuring zinc transporter 8 increased the number of autoantibody‐positive individuals by eight. Conclusions The present study provides the first evidence that Type 1 diabetes genetic risk score can be used to distinguish monogenic from Type 1 diabetes in an Iranian population with a large number of consanguineous unions. This test can be used to identify children with a higher probability of having monogenic diabetes who could then undergo genetic testing. Identification of these individuals would reduce the cost of treatment and improve the management of their clinical course., What's new? Studies in white European populations have recently shown that a genetic risk score for Type 1 diabetes has a high ability to discriminate between Type 1 diabetes and monogenic diabetes.The diagnostic utility of this genetic risk score in non‐European populations is unknown.This study provides the first evidence that the Type 1 diabetes genetic risk score discriminates children with monogenic diabetes from those with Type 1 diabetes in the Iranian population with a large number of consanguineous unions.The Type 1 diabetes genetic risk score can be used to improve the selection of non‐European children for monogenic diabetes testing, resulting in the correct diagnosis, improving their clinical management and providing families with recurrence risk information.

Background After the onset of type 1 diabetes mellitus (T1DM), preservation of the residual s-cell function can help good metabolic control. The aim of this study was to evaluate the effect of vitamin D and its receptor gene polymorphisms on residual s-cells function. Methods One hundred and one children with T1DM (new cases) older than 5 years were selected. Vitamin D receptor (VDR) gene polymorphisms, vitamin D (VD), fasting and stimulated C-peptide (FCP and SCP) levels were measured within 1.5 and 4.5 month after the diagnosis of disease. Kruskal-Wallis and Mann-whitney U test were used for comparing the study groups. Generalized estimating equation (GEE) model was used for the estimation of association between VD and VDR gene polymorphisms with FCP and SCP after adjustment for comorbid variables. Results The most frequent genotypes and alleles in TaqI, FokI, BsmI and ApaI polymorphisms were TT (50%) and allele T (68.88%), FF (59.2%) and allele F (77.04%), Bb (41.8%) and allele b (61.73%), and Aa (53.1%) and allele A (63.29%) respectively. In children with higher VD levels, the C-peptide (CP) levels were elevated. Also we observed: the tt genotype associated with increasing SCP levels compared with TT genotype; the bb and Bb genotypes were associated with increasing both FCP and SCP in comparison to BB; and the aa and Aa genotypes were associated with decreasing FCP in comparison to the AA genotype. Conclusions Sufficient levels of VD (more than 30 ng/ml) can preserve residual s-cells and insulin secretion.

OBJECTIVE Wolcott-Rallison syndrome (WRS) is an extremely rare autosomal recessive condition, characterized by permanent neonatal diabetes mellitus (PNDM) associated with skeletal dysplasia, growth retardation and liver dysfunction. WRS is caused by biallelic mutations in the gene encoding eukaryotic translation initiation factor 2alpha kinase 3 (EIF2AK3). METHODS As part of a comprehensive study on clinical and genetic investigation of neonatal diabetes in an Iranian population, 60 unrelated Iranian subjects referred with PNDM were analyzed. All the probands were screened for KCNJ11, INS, ABCC8 and EIF2AK3 using a polymerase chain reaction-based sequencing approach. RESULTS We identified 9 different variants in EIF2AK3 in 11 unrelated Iranian probands, of which 5 variants were shown to be novel and not reported previously. The diagnosis of WRS was made by molecular genetic testing and confirmed by clinical re-evaluation of the subjects. Clinical follow up of the affected individuals shows that in at least some of them, PNDM was associated with short stature, failure to thrive, neurodevelopmental delay, epilepsy and hepatic and renal dysfunction. There was a strong family history of neonatal diabetes in the families of the probands with a high mortality rate. CONCLUSION WRS is a common cause of PNDM in children of consanguineous parents. Furthermore, clinical diagnosis of WRS would have been delayed or possibly missed without genetic testing because this study shows that the associated features of WRS might be obscured by a diagnosis of PNDM. Therefore EIF2AK3 should be considered for any infant and young child with PNDM, particularly if the parents are related.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, for which efficient therapies are needed. In this study, PCOS was induced in rats by intraperitoneal administration of testosterone propionate (0.2 mg/kg). Indole-based compounds 5-hydroxy indole-2-carboxylic acid, N-acetyl-tryptophan, Tryptamine, l-Tryptophan and Tryptophol were administered for 8 weeks in the PCOS model, after what histopathological assessment of ovaries was performed. The number of primary follicles, corpus luteum, growing follicles and graafian follicles increased and the number and diameter of ovarian cysts decreased in all treated rats in comparison with untreated group. In conclusion, l-Tryptophan and Tryptophol were most efficient as potential therapeutic molecules.

Background: Due to lack of detailed standards of sexual maturity in individuals with Intellectual, sensory and motor disability in Iran and the importance of timing of onset of puberty in these individuals, a study is necessary. By knowing the onset of puberty, physiologic and behavioral changes can be traced in these people, as well as the potential impact of the puberty on the underlying disease can be considered. The aim of the study was to investigate of sexual maturation among boys of special schools of Tehran. Materials and Methods: Cross-sectional study was performed on children and adolescents male students in special school in Tehran at 2013. A random, multistage sample 0f 895 boy students of special schools was taken from 25 special schools in five districts of Tehran city. In this study, symptoms and stages of puberty were identified. Pubertal stages were assessed by visual inspection and palpation based on the rating scales of Tanner. In addition, demographic data such as age, height, weight were collected. Then the data were analyzed and mean age of onset of puberty was determined. Results: The mean age of onset of puberty in boys (Genitalia stage 2) was 13.12 ± 1.84 years and sexual maturation was completed at 16.57 ± 1.34 years. The average height at the onset of puberty (Genitalia stage 2) was 151.1 ± 9.91 cm and the average weight was 48.47 ± 10.14kg. The mean BMI for puberty onset was 20.89 ± 5.43. Conclusion: In our study, the mean age of puberty onset in boys with disabilities was 13.12 ± 1.84 years. Compared to the data from healthy boys, our findings indicate that the mean age of pubertal onset in boys with disabilities in special school is higher than that of their healthy counterparts.

Premature pubarche (PP) is the appearance of sexual hair in children before puberty. The PP phenotype may attribute to nonclassic congenital adrenal hyperplasia (NC-CAH). In this study, we investigated the role of CYP21A2 gene variants in patients with PP in the Iranian population. Forty patients (13 males and 27 females), clinically diagnosed with PP, were analyzed for molecular testing of CYP21A2 gene variants. Direct sequencing was performed for the samples. Also, gene dosage analysis was performed for the cases. Fourteen patients (35%) had a mutation of p.Gln318X and p.Val281Leu, out of which 10% had regulatory variants. Approximately 10% of the patients were homozygous (NC-CAH). 78.5% (11/14) of patients had trimodular RCCX of which 5 patients had two copies of CYP21A1P pseudogene. The prevalence of p.Val281Leu was higher than p.Gln318X in PP patients. In conclusion, CYP21A2 variant detection has implications in the genetic diagnosis of PP phenotype. The genetic characterization of the CYP21A2 gene is important for characterizing the variable phenotype of carriers and genetic counseling of PP and NC-CAH patients.

This community-based cross-sectional study was done on 1001 children and adolescents aged 6-18 years from Lorestan province randomly selected by multistage cluster sampling method. Children and their parents were interviewed using the Kiddie-Sads-Present and Lifetime Version (K-SADS-PL). Also, the comorbidities of psychiatric disorders were evaluated.According to obtained results, 25.1% of participants were diagnosed to have at least one psychiatric disorder. The prevalence of psychiatric disorders was not significantly different between the two sexes (OR=0.876, P=0.378) and three age groups (P0.05). this prevalence was significantly higher in rural areas than in urban areas (OR= 1.997, P=0) and was significantly lower in children of fathers with a high school diploma or higher education compared to children of less-educated fathers (P0.05). On contrary, it was significantly more prevalent in children of mothers with high school and bachelor's degrees compared to illiterate mothers. (p0.05). The most prevalent psychiatric disorders were oppositional defiant disorder (ODD) (5.9%), separation anxiety disorder (5.3%), and depressive disorders (5%). The most prevalent groups of psychiatric disorders included anxiety disorders (11.2%), behavioral disorders (9.4%), and mood disorders (5%). Behavioral disorders were highly comorbid with anxiety disorders (20.7%).Mental disorders affect a high proportion of children and adolescents in Lorestan province. There is a need for psychiatric facilities to provide for the needs of families to child mental health services.

Early onset of obsessive-compulsive disorder in childhood is bad news. That is why designing and testing various interventions that target this disorder at an early age is very important. In this regard, the present study aims to study the effectiveness of cognitive behavioral group therapy on children with obsessive-compulsive disorder. This quasi-experimental study consisted of pre-test, post-test, and follow-up stages. Out of the population of children 6 to 12 years old with obsessive-compulsive disorder referring to psychological counseling centers in Isfahan, 30 individuals were selected. Then they were randomly divided into two groups of experimental group who received cognitive behavioral therapy and control group. The experimental group received 12 sessions of group therapy intervention based on cognitive-behavioral model on a weekly basis. Yale-Brown Obsessive Compulsive Scale was filled by the subjects in pre-test, post-test, and follow-up stages. Analysis of variance with repeated measures was used to analyze the data. The results showed that cognitive-behavioral group therapy in all areas of obsession and compulsion of time, interference, discomfort, resistance, and control had a significant impact (α˂ 0.01 ). The results obtained in this study show the effectiveness of group therapy and group interventions in addition to other privileges of them. Key words : obsessive-compulsive disorder, group therapy, cognitive behavioral therapy, child, mother

BACKGROUND Obesity seems to be a critical issue nowadays because of its high prevalence and its adverse effects on health. There is some evidence indicating the relationship between obesity and lower serum 25-hydroxyvitamin D [25(OH)D] concentration. The aim of the present study was to examine serum 25(OH)D status of obese and non-obese Iranian children and compare their therapeutic response with identical oral vitamin D3 treatment. METHODS In a non-randomized clinical trial, serum 25(OH)D level of 45 obese and 45 non-obese Iranian children aged 2-14 years was measured. Those with serum 25(OH)D status

Background: Sick euthyroid syndrome (SES) is the most common endocrine disorder in critically ill patients. It has been shown that the decrease in T4 levels correlates with disease severity and prognosis. Whether SES is a compensatory response to the disease course or needs to be treated is not known yet. Objectives: To our knowledge, there are only a few studies on critically ill infants and children investigating the correlation between thyroid function and disease severity as well as its outcome. Therefore, this study aimed to investigate thyroid hormone levels in critically ill patients. Methods: In this study, thyroid function tests including thyroid stimulating hormone (TSH), total T3 (TT3), free T3 (FT3), total T4 (TT4), free T4 (FT4), and reverse T3 (rT3) were measured in 35 critically ill children admitted to intensive care unit (ICU) on days 1 and 3 of admission. Disease severity was evaluated using pediatric logistic organ dysfunction score (PELOD). Then the patients were divided into groups of survivors and non-survivors and the results were compared between these two groups accordingly. Results: Thirty-five patients, including 19 (54.3%) female and 16 (45.7%) male, with the mean age of 2 years (SD: ± 3.8 years, range: 4 months - 15 years) had entered the study based on the inclusion criteria. 25 (71.6%) patients were transferred from PICU to other wards and 10 (28.4%) patients died. Age and sex were not statistically different in survivors and non-survivors (P > 0.05). It was revealed that there was a significant reduction in mean TT3 levels in non-survivors compared to survivors on the first day of admission (P = 0.007). On the third day of admission, however, a significant reduction in TT4 levels were seen in non-survivors (P = 0.03). Conclusions: Thyroid function assessment, especially TT3 on the first day and TT4 on the third day of admission, along with PELOD score, might be helpful in predicting disease outcome and patient’s survival.

Quality of life (QOL) measures can be used to make sound clinical decisions after reconstruction of the anterior cruciate ligament (ACL). The purpose of the present study was to translate and cross-culturally adapt the Anterior Cruciate Ligament Quality of Life (ACL-QOL) questionnaire into the Persian language and to evaluate its psychometric properties.The process of translation and cross-cultural adaptation followed the World Health Organization method. One hundred and forty-five patients with ACL reconstruction (ACL-R) filled out the Persian versions of ACL-QOL and the SF-36 Questionnaire. The measurement properties of internal consistency, agreement, criterion validity, floor and ceiling effects were measured. 40 out of 145 patients with ACL-R completed the Persian version of the ACL-QOL questionnaire twice for the test-retest reliability.The questionnaire had high internal consistency (Cronbach's α = 0.96). The intraclass correlation was excellent for reliability and agreement in five domains and overall score (ICC 0.87, 0.74, 0.90, 0.85, 0.81 and 0.89; p 0.001). The standard error of measurement and the minimum detectable change were found to be 3.28 points and 9.9 points, respectively. There was a strong correlation between each item and the total score of the Persian version of ACL-QOL questionnaire. The questionnaire showed strong and moderate criterion validity (r = 0.61, r = 0.37) with SF-36 physical component score and mental component score, respectively. No ceiling and floor effects were observed.Persian version of the ACL-QOL questionnaire has acceptable reliability and validity and can be used in assessing Iranians quality of life after ACL reconstruction.

Most patients with Wolfram syndrome carry mutations in WFS1, while a lower percentage present a mutation in CISD2 (also known as WFS2). The aim of this study was to investigate the presence of mutations in exon 8 of WFS1 gene in two Iranian patients with Wolfram syndrome (WFS). In this study using polymerase chain reaction (PCR) followed by direct sequencing, we screened the entire length of WSF1 gene exon 8 for presence of mutations. Patients included were two male subjects who developed diabetes mellitus earlier than the age of 8 years old, showing early-onset diabetes, followed by reduced visual acuity, deafness, and diabetes insipidus. The presence of two missense mutations G736D and R629W were confirmed. These mutations have been previously reported in patients with WFS in other populations. Identification of pathogenic mutations in patients with Wolfram syndrome will be helpful in earlier diagnosis of the disease and in understanding the frequency of mutations in various populations and their relation with clinical features of Wolfram syndrome.

This study was designed to evaluate the reproductive toxicity of Cassia absus seeds, which have been used in Persian folk medicine. Female rats in treatment groups (N = 5) received C. absus n-hexane fraction (CAF) at oral doses of 100, 200, and 500 mg/kg b.wt./day, once per day on days one to five post-coitum (pc). The control group received 0.2 mL of olive oil (vehicle). Fertility, maternal index, hormone level, and teratogenicity were evaluated. Phytoconstituents of the seeds were detected by HPTLC and GC-MS. The presence of phytoprogesterones was evaluated by docking software. The fertility index and number of fetuses in treated groups decreased significantly. Missed abortion was 50% after administration of 500 mg/kg/day of CAF. The maternal body weight, uterine weight, and levels of FSH, LH, and estradiol exhibited insignificance changes. The serum concentration of progesterone also changed significantly in a dose-dependent manner. No teratogenic effect was found. Oleic acid (35.89%) and linoleic acid (24.22%) were the major constituents of the seed oil. In addition, chaksine and β-sitosterol showed potential phytoprogesteronic properties in docking studies. The reproductive toxicity of C. absus seeds may be related to a hormonal imbalance, a decline in the fertility index, and an increase in the rate of missed abortions of fetuses.

PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases, including type 1 diabetes (T1D) which is a T-cell-mediated disease.The present study was aimed at genotyping of an Iranian population for five polymorphisms of the PTPN22 gene.The study population consisted of 99 T1D patients and 100 healthy controls. We genotyped five single-nucleotide polymorphisms (SNPs) (rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601) of the PTPN22 gene.Regarding the variant rs2476601, genotypes AG and GG were increased and decreased in T1D patients compared with controls, respectively. Further, alleles G and A of this SNP were found to be decreased and increased in T1D patients, respectively (p value = 0.001). However, T1D and control groups did not differ on genotype distribution or allele frequency for other investigated SNPs.The PTPN22 rs2476601 minor allele (A) was associated with T1D in Iran, accounting for its pathophysiology in autoimmune diseases.

Introduction: The strict control of blood glucose levels in adolescents with Type 1 Diabetes Mellitus (T1DM) is accompanied with a considerable long term decrease in microvasular and macrovascular complications. Aim: This study was conducted to investigate the effect of metformin as an adjunct therapy in adolescents with poorly controlled Type 1 diabetes. Materials and Methods: It was a quasi-experimental (an uncontrolled before and after) study. The study population consisted of the patients aged over 10 years with T1DM. Metformin tablet was added to patient’s insulin therapy for 12 months. Haemoglobin A1c protein was measured in the beginning of the study and repeated with three months intervals till the end of it. Insulin dosage, Body Mass Index (BMI), serum lipid, creatinine and lactate level were measured twice; in the beginning of the study and at the end of it (after 12 months). Data was analysed by SPSS (version 18) software. Pairedt-test, Wilcoxon signed ranks test and Repeated Measure ANOVA were used to examine the study’s hypothesis. A p-value

H syndrome is a hereditary disease transmitted in an autosomal recessive pattern.It consists of two major clusters of cutaneous and systemic manifestations [1,2].The symptoms include short stature, hyperpigmentation of skin, hypertrichosis, deafness, hypogonadism, anomalies of heart, hyperglycemia(insulin dependent diabetes mellitus) and hepatosplenomegaly [1]. H syndrome is the result of mutations in theSLC29A3 gene that can be homozygous or compound heterozygous. The SLC29A3 gene is located on chromosome 10q22 and encodes a transporter protein that causes passive transportation of nucleosides which is critical for several functions such as DNA and RNA repair [3–5]. Several different mutations withinSLC29A3 can cause H syndrome. In this report, we present a 4.5 year old girl diagnosed with H syndrome based on genetic investigation.

Background Primary antibody deficiency (PAD) is the most common group of primary immunodeficiency disorders, resulting from different defects in the development and function of B cell lineage. Common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) are two of the major types of PADs. Optimal growth and subsequently bone health could potentially compromise due to the interference of several factors in PAD with childhood onset. In the present study, our aim was to evaluate bone mineral density (BMD) of patients with CVID and XLA. Methods BMD of 37 CVID and 19 XLA patients was examined. Total BMD was determined by dual-energy X-ray absorptiometry and the calculated scores were compared internally and externally with age-sex matched and ethnic-specific reference. Related factors associated with bone density including immune-related complications, serum calcium, phosphate, total alkaline phosphatase, 25(OH) vitamin D and parathyroid hormone levels were recorded. Results The median age at the time of study was 20 years among all patients and was not statistically different between CVID and XLA groups and the mean of body mass index (BMI) was 19.4±4.6 kg/cm². Thirty-eight (67.9%) of total patients had normal BMD and 18 (32.1%) patients had a low BMD. BMI was positively correlated with BMD at lumbar spine and femoral neck. The number of low BMD patients in CVID (40.5%) group was more than the XLA (15.8%). Conclusion Beside nutritional, gastrointestinal and infectious complications which are shared in both groups of patients, CVID patients are more prone to alteration of BMD due to association with lymphoproliferative and endocrine diseases. Therefore routine evaluation of bone density and treatment adjustment should be considered in all PAD patients particularly in CVID patients.

Background: Inborn errors of metabolism (IEM) are disorders caused by genetic mutations of the normal metabolic pathways. Objectives: The aim of this study was to investigate clinical findings and laboratory tests for IEMs to determine a proper clinical and laboratorial approach to these disorders. Methods: This descriptive study involved 180 patients with suspected IEM at the children’s medical center (CHM) in Tehran. The patients’ information was recorded in special forms, and three levels of examinations were performed. Data were subjected to frequency, percent, and chi square tests using SPSS version 17. Results: The study sample included 87 (48.3%) female patients and 93 (51.7%) male patients. The most common (20%) clinical presentation of patients with IEMs was poor feeding or failure to thrive, and the frequency of the condition in children younger than age 1 year was approximately 35%. Eighty percent of patients received a definitive diagnosis by the first and second level of examination. The most common (17%) disorders were proponic acidemia, methylmalonic acidemia (14%), and urea cycle disorder (14%). Conclusions: Considering the non-specific primary presentation of IEMs and the importance of clinical diagnosis other than specific laboratory tests, it is necessary to develop a general guide for an approach to IEM that provides appropriate management for high-risk families and infants.

Background There is limited data on sexual maturation among girls with intellectual, sensory, or physical disabilities. Objectives The present cross-sectional study was conducted to assess the sexual maturation of girls with these disabilities in special schools. Methods In this cross-sectional study, we evaluated the onset and progression of sexual maturation in 642 six to 18-year-old girls with intellectual, sensory, or physical disabilities from special schools in Tehran. The participants were selected by multi-stage random sampling. Pubertal stages were assessed by visual inspection and palpation based on the rating scales of Tanner. Stage two (breast budding and pubic hair growth) and stage five were considered the onset and end of puberty, respectively. Results The mean ages of onset of puberty indicated by breast budding (B2 stage) and by pubic hair growth (P2 stage) were 10.8 ± 1.48 and 10.79 ± 1.64 years, respectively. The process of puberty based on breast budding and pubic hair growth was completed at 15.58 ± 1.85 and 15.59 ± 1.8 years, respectively. The average height at the onset of puberty (stage B2) among participants was 128 ± 28.79 cm and the average weight was 8.31 ± 36.47 kg. Conclusions Among our patients, the mean ages of onset of puberty indicated by breast budding (B2 stage) and by pubic hair growth (P2 stage) were 10.8 ± 1.48 and 10.79 ± 1.64 years, respectively. Compared to the data from healthy Iranian girls, our findings indicate that the mean age of pubertal onset among schoolgirls with disabilities is slightly higher than that of their healthy counterparts.

There is a number of syndromes, associated with proptosis, micrognathia, low-set ear and chest deformity. Herein, we report a 9-year-old female with such phenotype who was presented with a vaginal neuroma. The result of karyotype showed 47XX, with extra marker chromosome 22. Although such a manifestation had not been reported in the literature, it should be considered as a very rare manifestation of the disease.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also named as autoimmune polyglandular syndrome (APS) type 1, is a rare autosomal recessive disorder caused by mutations in autoimmune regulator (AIRE) gene. It is distinguished by an immune-mediated damage of endocrine tissues, chronic candidiasis, and ectodermal disorder. APECED has been shown to be frequent in some populations including Iranian Jews. Here we report three cases of APECED from two independent Iranian Muslim families. Addison’s disease, hypoparathyroidismand mucocutaneous candidiasis were shared clinical manifestations in all patients. Mutational analyses have demonstrated a novel homozygous splice site mutation (c.1095+2T>A) in intron 9 and a previously identified homozygous nonsense mutation (c.415C>T) in exon 3 of patients respectively. Future studies are needed to evaluate the frequency of these variants in Iranian APECED patients which would facilitate genetic counseling as well as prenatal diagnosis.

Specific alleles at the HLA-DRB1, -DQA1, and -DQB1 loci seem to be associated with variable risks of developing type 1 diabetes (T1D). This study assessed the distribution of HLA-DR and -DQ alleles among Iranian T1D patients and healthy controls. In this study, HLA-DRB1, -DQA1, and -DQB1 alleles were determined in 100 children with T1D and 100 unrelated healthy controls. The following alleles were found to have a strong positive association with T1D: DRB1*0301, DRB1*0401, DRB1*0402, DQA1*0301, DQA1*0501, DQB1*0201, and DQB1*0302. Meanwhile, protective associations were found for DRB1*1001, DRB1*1101, DRB1*15, DRB1*16, DQA1*0102, DQA1*0103, DQB1*0301, DQB1*0501, and DQB1*0602 alleles. The haplotypes found most frequently among patients with T1D were DRB1*0301-DQA1*0501-DQB1*0201, DRB1*0401-DQA1*0301- DQB1*0302, and DRB1*0402-DQA1*0301-DQB1*0302, whereas DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*16-DQA1*0102- DQB1*0501 haplotypes were negatively associated with the disease. These results confirm the previously reported association of specific HLA-DR and HLA-DQ alleles and haplotypes with T1D in Iranian population. The notable difference was the identification of DRB1*16-DQA1*0102-DQB1*0501 as a protective haplotype and the absence of a negative association of DRB1*1301-DQA1*0103-DRB1*0603 with T1D.

Hyperostosis-hyperphosphataemia syndrome (HHS) is a rare autosomal recessive metabolic disorder, characterized by recurrent painful swelling of long bones, periosteal new bone formation and cortical hyperostosis or intramedullary sclerosis, hyperphosphatemia and low intact fibroblast growth factor 23 (FGF23) protein levels. It is caused by mutations in 2 genes, N-acetylgalactosaminyltransferase 3 (GalNAc-transferase; GALNT3) and FGF23. We have performed mutation analysis of the GALNT3 and FGF23 genes in a patient with HHS and detected a homozygous mutation in exon 3 of FGF23 gene (NM_020638.2: c.471C>A) which results in amino acid change from phenylalanine 157 to leucin (p.F157L) in receptor interaction site.

It is important to reduce keeping costs and hold up unscheduled downtimes for machinery. So knowledge of what, where and how faults occur is very important. Fault detection and diagnosis are necessary for implementing CBM (condition base model) Best classifier systems which are considered as one of the most significant advances in pattern classification in recent years. We exposure new algorithm in this paper, this new algorithm have 3 steps. In the First step used wavelet Entropy for make wavelet tree with coefficient in each node. In second step using wavelet tree fused data with maximum coefficient in wavelet tree and in step three with output of fusion function we classification this fusion data by kernel method. This algorithm have best time study because the time of search algorithms is, D is depth of wavelet tree. Our proposed fusion strategies take into account that a Wavelet-Entropy by finding the optimal kernel size with maximal margin. Then a kernel Machine classifier is trained.

Fanconi–Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, impaired utilization of glucose and galactose, rickets, and severe short stature. It has been shown to be caused by mutations in GLUT2 gene, a member of the facilitative glucose transporter family. Here, we report an Iranian family with 2 affected siblings. The clinical findings in the patients include developmental delay, failure to thrive, hepatomegaly, enlarged kidneys and rickets. A novel 6 nucleotide deletion (c.1061_1066del6, p.V355_S356del2) is shown to be segregated with the disease in this family.

Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare autosomal recessive metabolic disorder caused by mutations in the GALNT3 and FGF23 genes. The main features of this disorder include painful swelling of long bones, increased renal reabsorption of phosphate but normal renal function and vitamin D and parathormone levels. Previously, we reported a novel missense mutation in the FGF23 gene in a patient suffering from HHS. In the present report, we demonstrated the same mutation (c.471C>A) in two other cases of HHS with similar clinical manifestations. As this nucleotide change has not been reported previously, it can be a population specific mutation in Iran that can facilitate carrier testing and prenatal diagnosis of HHS.

Type 1 diabetes is recognized as an autoimmune inflammatory disease and low grade inflammation is also observed in type 2 diabetic patients. Interleukin 17 (IL-17) is a new player in inflammation. Th17 cells, as the main source of IL-17, require transforming growth factorβ(TGF-β) and interleukin 23 (IL-23). The aim of this study was to investigate serum IL-17, IL-23 and TGF-βlevels in diabetic patients and controls. In this case-control study, serum levels of IL-17, IL-23, and TGF-βwere measured in 24 type 1 diabetic patients and 30 healthy controls using the ELISA method. Simultaneously, the same methodology was used to compare serum concentration of these three cytokines in 38 type 2 diabetic patients and 40 healthy controls. There was no significant difference between serum levels of IL-17 and IL-23 cytokines between cases and controls. However, TGF-βwas significantly lower in type 1 diabetic patients (P<0.001). Serum IL-17 and IL-23 levels demonstrate no association with type 1 and type 2 diabetes, but, in line with previous studies, TGF-βlevels were lower in type 1 diabetic patients.

Aims The purpose of this study was to evaluate adherence to insulin therapy in patients with diabetes. The underlying factors affecting insulin injection omission among patients with type 1 or 2 diabetes were also investigated. Methods This cross-sectional study has been conducted on 507 patients with diabetes. Adherence to insulin therapy was measured by the 8-Item Moriskey Medication Adherence Scale (MMS) and the autocompliance method. Furthermore, socio-demographic, disease and injection-related barriers to insulin injection were assessed. Results Based on the Morisky Green test, 14.3% and 28.8% of patients with type 1 and 2 diabetes respectively had low adherence to insulin therapy. However, almost all patients were adherent according to the autocompliance method. Different factors showed a significant association with insulin compliance in both groups. Conclusions The current study suggests acceptable adherence to insulin therapy among patients with type 1, and poor adherence in patients with type 2, diabetes. Our findings regarding barriers with significant effect on insulin adherence may be useful to identify patients at risk for low compliance, and to guide the design of proper strategies to improve adherence and the consequential clinical outcomes.