Bone density, fractures and the associated factors in iranian children and adolescent with Osteogenesis Imperfecta.

BACKROUND: Osteogenesis imperfecta(OI) is a frequent bone fragility disorder in children. The purpose of this study was to assess the BMD and Vitamin D level in children with OI in southern Iran. METHOD: This case-control study was conducted on 23 children, clinically diagnosed as osteogenesis imperfecta and 23 age- and gender-matched healthy controls. Demographic and anthropometric data, biochemical parameters, puberty, sun exposure and physical activity were assessed. Bone mineral density (BMD) was measured by Dual-energy X-ray absorptiometry (DXA). Data analysis was done by SPSS22. RESULTS: Forty-three point four percent of OI patients and fifty-six point five percent of control group had vitamin D deficiency (P = 0.376). Thirteen OI patients (56%) had low bone mass for chronological age in lumbar area (P < 0.001). Fracture episodes during treatment was significantly influenced by time of Pamidronate start, courses of Pamidronate injection, puberty and sun exposure (P values = 0.015, 0.030, 0.044 and 0.032, respectively). Fracture episodes during treatment had significantly increased in patients who had received Pamidronate more than 3 years compared with those received less than 3 years(P values = 0.047). CONCLUSIONS: This study showed that vitamin D deficiency is prevalent amongst OI children in southern Iran. More than half of the OI children had low bone mass for chronological age in lumbar area, despite receiving bisphosphonate therapy. The present results revealed that early initiation of Pamidronate and number of Pamidronate courses are associated with lower fracture rate. However, treatment period more than 3 years can have adverse effect on fracture rates.

A New Mutation Causing Severe Infantile-Onset Pompe Disease Responsive to Enzyme Replacement Therapy.

Pompe disease (PD), also known as "glycogen storage disease type II (OMIM # 232300)" is a rare autosomal recessive disorder characterized by progressive glycogen accumulation in cellular lysosomes. It ultimately leads to cellular damage. Infantile-onset Pompe disease (IOPD) is the most severe type of this disease and is characterized by severe hypertrophic cardiomyopathy and generalized hypotonia. Mutations in the acid alpha-glucosidase (GAA) gene, located at locus 17q25.3, are responsible for the disease leading to reduced activity of the acid alpha-glucosidase enzyme. To date, approximately 400 pathogenic mutations have been reported in the GAA gene. The aim of this study is to report a novel nonsense mutation in exon 4 of the GAA gene in an Iranian child suffering from IOPD. The patient was a female neonate with hypertrophic cardiomyopathy and a positive family history of IOPD. After definite diagnosis, enzyme-replacement therapy (ERT) was started for the patient, who was 2 months old. Now at the age of 20 months, she has had good growth and development and her echocardiographic parameters are within the normal range. This report shows that IOPD patients with this mutation can be treated with ERT successfully.

CYP21A2 Gene Analysis in Southern Iranian CAH Patients and a Brief Review of the Mutation Spectrum.

Background: CYP21A2 gene mutations are responsible for more than 95% of Congenital Adrenal Hyperplasia (CAH) disorders with autosomal recessive inheritance. Most of these pathogenic mutations originate from the CYP21A1P, a neighboring pseudogene with 98% homology, due to unequal crossing over or gene conversion events. Mutation identification of the gene could be beneficial for accurate diagnosis and outcome prediction. Methods: Twelve unrelated patients with CAH diagnosis were recruited for genetic counseling. To ensure distinct amplification of the CYP21A2 gene rather than its pseudogene, the complete sequence of the gene was amplified through two overlapping fragments by specific primers. The entire sequences were screened by direct Sanger sequencing using new sequencing primers. Results: Only two pathogenic point mutations were identified. The c.293-13C>G, also known as In2G, and the c.955C>T mutations were found in 37.5 and 33.3% of alleles, respectively. One patient showed homozygous gene deletion. We also reviewed recent reports on CYP21A2 gene mutations in Iran. Conclusion: Evaluating the ethnicity-specific gene mutation data is significant for populations with diverse ethnic groups including the Iranian population. Although several common mutations have been reported as causative mutations among CAH patients, identifying only two common point mutations in Fars province would help prioritize exon sequencing and reduce the cost and time of genotyping.

Inborn Errors of Metabolism Associated With Autism Among Children: A Multicenter Study from Iran.

OBJECTIVE: This study aimed to find the common inborn errors of metabolism in Iranian patients with autism spectrum disorder. METHODS: In this cross-sectional multicenter study, 105 children and adolescents with autism spectrum disorder from six centers in different cities of Iran were enrolled between August, 2019 and October, 2020. Metabolic screening, including measuring plasma levels of amino acids, acylcarnitines, creatine, and guani-dinoacetate, and urinary levels of organic acids, purines, and pyrimidines was performed. Other data, including age, parental consanguinity, history of seizure, developmental mile-stones, and physical examination, were also recorded. RESULTS: An inborn error of metabolism was found in 13 (12.4%) patients. Five patients (4.8%) had cerebral creatine deficiency syndrome, 4 (3.8%) had arginine succinate aciduria, 2- methylbutyryl glycinuria, short-chain acyl-CoA dehydrogenase deficiency, and combined methylmalonic aciduria/malonic aciduria. There was a strong association between positive meta-bolic evaluation and parental consanguinity, history of seizures, microcephaly, and delayed development. CONCLUSIONS: Our results suggest that metabolic screening should be performed in the cases of autism associated with parental consanguinity, developmental delay, and a history of seizures. The assays to be considered as a screening panel include plasma or blood amino acids, acylcarnitines, creatine and guanidinoacetate, and urinary levels of organic acids.

Role of Selenium Deficiency in Pediatrics with Acquired Hypothyroidism.

BACKGROUND: Although selenium is one of the nutrients that has an important role in the metabolism of thyroid hormones, it has been investigated in rare studies. This study aimed to evaluate role of selenium deficiency in children and adolescents with acquired hypothyroidism. METHODS: This case and control study was conducted on 60 acquired hypothyroidism and 60 healthy children who had been referred to the pediatrics endocrine clinic in Shiraz, Iran, from November 2018 to April 2019. Some information such as age, gender, weight, height, duration of disease, and level of plasma selenium were recorded. Plasma selenium level was measured by atomic absorption spectrophotometer. Data were analyzed using SPSS software 21.0. RESULTS: The mean of selenium level in the case and control groups were 93.77 ± 24.90 µg/dl and 85.96 ± 25.20 µg/dl, respectively. There was no significant difference between the two groups in the mean levels of selenium. Independent t-test showed no significant difference in the mean levels of selenium in male and female samples in the case group, but this difference was significant in the control group. CONCLUSION: Selenium deficiency may not have significant role as a cause of acquired hypothyroidism in pediatric and adolescent age group, in south of Iran. Thus, it does not seem necessary to routinely check the level of selenium for patients with thyroid dysfunction.

Uncovering Cardiac Involvement in Childhood Diabetes: Is it Time to Move Toward Speckle Tracking Echocardiography in Childhood Diabetes Management?

CONTEXT: One of the most common endocrine disorders in children is diabetes which is the leading cause of premature cardiovascular disease in adulthood. AIMS: This study is aimed to investigate the extend of cardiac involvement in diabetic children by speckle tracking echocardiography (STE) in comparison to two-dimensional (2D) echocardiography and routine laboratory data. SETTINGS AND DESIGN: A cross-sectional study conducted on patients under 18 years of age who deal with type one diabetes mellitus for more than 5 years. SUBJECTS AND METHODS: To compare the STE results, we included the STE data of 25 normal age-matched children. All patients underwent laboratory analysis for lipid profile, blood sugar, and 2D echocardiography plus STE. STATISTICAL ANALYSIS USED: Two-sample independent t-test, Chi-square test, logistic regression test, Spearman's rank correlation coefficient, and the Pearson correlation coefficient. RESULTS: From March 2018 to 2019, we included 53 patients, mean age 15.8 ± 0.39 years and 52.8% female, and 25 nondiabetic control in this study. STE revealed global longitudinal strain (LS) -18.4 versus - 24.2 for patient (44 valid cases) versus control group, respectively, with significant statistical difference. Diabetic patients had lower LS in all segments compared to the control group. CONCLUSIONS: STE has very high sensitivity to detect cardiac involvement far earlier than 2D echocardiography. None of the routine biomarkers or demographic features can predict cardiac involvement based on segmental abnormalities of STE. Active investigation to clear the remote impact of STE abnormalities and its practical role in childhood diabetes management is highly recommended.

Aortopathic effect of androgenic anabolic steroids.

BACKGROUND: Anabolic androgens have been reported to be associated with cardiovascular complications. One study revealed that increase in vascular stiffness in bodybuilders is associated with anabolic androgens and improvement in vascular function may occur following anabolic androgens discontinuation. The aim of this study was to investigate any possible relation between aortic elastic properties and anabolic androgens. METHODS: Study population was divided into 3 groups: Group-1 [n = 35] consisted of bodybuilders who denied any current or previous use of anabolic androgens. Group-2 [n = 18] was bodybuilders with regular using of anabolic androgens for at least 2 year prior to the start of our study. Group-3 was 13 healthy age-matched sedentary men as a control group. Cardiac echocardiography was performed in the bodybuilders and controls and indexes of aortic function were calculated. RESULTS: Aortic stiffness was approximately twofold higher in anabolic androgens user bodybuilders compared with drug-free bodybuilders [P < 0.001]. CONCLUSION: The present study demonstrates that chronic anabolic androgens use clearly produces significant decrease in the elastic properties of aorta.

Optimal Frequency to Screen Celiac Disease amongst Patients with Type 1 Diabetes Mellitus: A Multicenter Study.

AIMS: Celiac disease (CD) is frequent amongst patients with type 1 diabetes mellitus (T1DM). Since there is a disagreement on the optimal interval and frequency to perform screening tests for CD among diabetic patients, this study aimed to evaluate these issues amongst patients with T1DM. METHODS: This retrospective cohort study was conducted in seven referral diabetic centers in different cities of Iran from January 2020 to January 2021. Data belonging to 106 patients who were affected by both T1DM and CD was collected. The time interval between CD diagnosis and diabetes (IBCD), the age of diabetes onset, and any associated diseases, symptoms, and family history of T1DM and CD were recorded and analyzed. RESULTS: Results show that 45% of the patients with CD were diagnosed during the first year of diabetes onset; furthermore, 18% and 16% of the patients with CD were diagnosed in the second or third year after being diagnosed with diabetes. In addition, another 18% of patients with CD were diagnosed during the fourth till the eighth year after diabetes onset. Moreover, there was a negative relationship between the age of T1DM diagnosis and IBCD. Most participants were asymptomatic at the time of CD diagnosis. CONCLUSIONS: Screening tests to detect CD amongst patients with T1DM should continue for at least eight years after the initial T1DM diagnosis, especially those affected at a younger age.

Effect of pubertal suppression on linear growth and body mass index; a two-year follow-up in girls with genetic short stature and rapidly progressive puberty.

OBJECTIVE: Gonadotropin-Releasing Hormone agonists (GnRHa) are used to improve the final adult height in short stature children. There are limited studies which address the potential side effect of these agents: excessive weight gain. We have followed girls with rapidly progressive puberty receiving GnRHa and results were focused on the effect of treatment on final height, weight and body mass index Methods: Thirty girls between 8.5 and 12 years with short stature and predicted adult height of less than 155 cm were enrolled in the study. All had rapidly progressive puberty. Weight and height measurements were done at the beginning of treatment, 6 and 12 months after starting and 6 and 12 months after the cessation of treatment. Bone age and stages of puberty were estimated at the beginning of treatment, after 12 months of starting and 12 months after the treatment was stopped. Findings : Predicted adult height (PAH) changes during treatment were not significant. There was no significant difference between final height and weight according to the body mass index (BMI), PAH or bone age. CONCLUSION: We conclude that girls with genetic short stature and rapidly progressive puberty will not benefit receiving a one-year course of GnRHa and there is no significant difference between the final height and final weigh among children according to BMI.

QT Dispersion and T Wave Peak-to-end Interval Dispersion in Children with Kawasaki Disease.

BACKGROUND: The main complication of Kawasaki disease is the Coronary Artery (CA) involvement and long term follow up of patients depends on the severity of coronary arterial aneurysms, ischemia, and thrombosis. Early diagnosis of these complications can lead to a more desirable outcome for patients. Myocardial ischemia can prolong QT dispersion and increase the risk of cardiac arrhythmias as well as sudden cardiac arrests. Also, T wave peak-to-end (Tp-Te) interval dispersion, which provides a valuable index of transmural dispersion of repolarization, can trigger the arrhythmia. MATERIALS AND METHODS: We evaluated the non-corrected QT interval dispersion (QTD) and the corrected QT (QTc) dispersion and measured Tp-Te interval dispersion in 49 Iranian children (28 males and 21 females) with the diagnosis of Kawasaki disease (KD) in the acute phase and 49 age-matched controls in a prospective study from 2009 to 2012. Student's t-test and Pearson correlation were used to analyze the data. All the statistical analyses were performed through the SPSS 16. Besides, P<0.05 was considered as statistically significant. RESULTS: Patients with KD had significantly longer QTc dispersion (0.099±0.055 s versus. 0.040±0.018 s; P<0.001), non-corrected QT dispersion (0.075±0.046 versus 0.042±0.019; P<0.001), and Tp-Te dispersion (0.047±0.054 versus 0.022±0.011; P=0.015). The patients with elevation in white blood cell count (above 15000) had a statistically significant increased in QTD (P=0.011). No significant correlation was found between coronary involvement and repolarization indexes. CONCLUSIONS: In conclusion, the QT interval (corrected or non-corrected) and the Tp-Te dispersion significantly increased in the patients with KD which shows repolarization changes during the acute phase of KD. However, there is no correlation between the QT interval and the coronary involvement.

Congenital hypothyroidism: a review of the risk factors.

This study was aimed to evaluate the situation of congenital hypothyroidism (CH) in Guilan using the screening program and determine the correlation of CH with birth weight, gestational age and seasonality. During 2006 to 2010, in Guilan province, neonatal screening for CH by measurement of serum TSH level was performed in 3-5 days after birth. All neonates with TSH level ≥ 5mu/l were referred to endocrinologists and serum TSH, T3 and T4 were measured. Based on public health data and profiles, total number of newborns, gestational age, route of delivery, birth season and birth weight in all screened neonates was reviewed and for ones with CH, their TSH measurements was also recorded. During 5 years, 119701 neonates were screened and CH was confirmed in 10.8% (221) of the referral cases (prevalence=1:542). No significant statistical difference was seen between gender and birth season among patients with CH and the rest of the population. Interestingly, low birth weight (LBW) (31% vs. 4.9%, P<0.01), postdate delivery (1.4% vs. 0.2%, P<0.01) and macrosomia were more prevalent in CH versus normal population (Odds ratio for post-date delivery was 6.9 and for LBW was 3.2). Rate of normal vaginal delivery (NVD) was significantly higher in neonates with CH compared to normal population (39.2% vs. 29.2%, P=0.01). LBW, postdate delivery and macrosomia are risk factors for CH. No association between sex, birth season or caesarian section delivery was seen.

Serum resistin level in obese male children.

Objectives. Resistin is a member of cysteine-rich molecules. Several studies have been carried out to determine the biological effect of resistin, nevertheless a significant number are animal studies. All the studies performed regarding the relationship between serum resistin and obesity were merely accomplished in women. To the best of our knowledge, there is no survey on the correlation of the serum resistin level and obesity in male children. The aim of the present study is to assess serum concentration of resistin in obese male children. Methods. Between June 2009 and January 2010, we enrolled 42 randomly selected obese male students (body mass index (BMI) >95th percentile, age 15.7 ± 1.5). Thirty-eight healthy age-matched male students with normal BMI (<85th percentile) were selected as a control group for the purpose of comparison of the serum resistin levels. Results. Serum resistin levels were measured in obese and control group. No significant difference was found between resistin levels of the 2 groups (obese: 9.21 ± 5.6 ng/mL versus normal: 9.83 ± 4.3 ng/mL; P = .582). There was no significant correlation between serum resistin level and BMI. Assessing the resistin level in male subjects was the distinct feature of our study. The outstanding finding of this research is that there is no correlation between serum resistin level and obesity. Conclusion. We have demonstrated that there is no correlation between obesity in male children and resistin level. Consequently, metabolic abnormalities of insulin resistance seen in obese male patients are not related to resistin.

Spectrum of inherited bleeding disorders in southern Iran, before and after the establishment of comprehensive coagulation laboratory.

The objective of the present study was to determine the pattern of inherited bleeding disorders in southern Iran and evaluate the effect of a comprehensive coagulation laboratory and related efforts. A total of 545 patients with inherited bleeding disorders were evaluated during 1992-2007 by a cross-sectional study. Data were collected by a data-gathering form. Statistical analysis was done using Statistical Package for the Social Sciences version 15. A P value less than 0.05 was considered statistically significant. Overall 411 patients had common bleeding disorders including 326 hemophilia A, 46 hemophilia B, and 39 von Willebrand disease. Seventy-nine patients had rare coagulation disorders including deficiency of factor VII (n = 26), factor X (n = 18), factor XIII (n = 9), factor I (n = 9), factor XI (n = 7), factor V (n = 4), combined factor VIII and factor V (n = 4), and combined factor X and factor VII (n = 2). Fifty-five patients had platelet disorders including 23 with Glanzmann's thrombasthenia, 15 with Bernard-Soulier syndrome, and 17 with other platelet disorders, most of which (45) were diagnosed after the establishment of the comprehensive coagulation laboratory. Annual mean number of new diagnosed patients with common and rare bleeding disorders increased from 29 +/- 4 to 38 +/- 17. The ratio of the patients diagnosed with rare bleeding disorders to common bleeding disorders significantly increased after the establishment of the comprehensive diagnosis laboratory (P < 0.001).It seems that implementation of collaborative projects by the Shiraz Hemophilia Society and the establishment of the comprehensive coagulation laboratory and treatment centers have been successful in increasing diagnosis of the inherited bleeding disorders and consequently better management of the patients.