Hossein Moravej

Bruck syndrome - a rare syndrome of bone fragility and joint contracture and novel homozygous FKBP10 mutation.

Bruck syndrome is an autosomal recessive syndrome consisting of bone fragility and congenital joint contractures. According to the genotype, it has been classified into types 1 and 2. Recently, mutations in FKBP10, localised to chromosome 17q21, have been identified in some patients of Bruck syndrome. Twenty-seven patients of this syndrome have been reported so far. We present a new patient of this syndrome, with frequent fractures, congenital joint contractures, kyphoscoliosis, bilateral clubfoot, and pectus carinatum. The clinical and genetic features of all previously reported cases are also reviewed.

Evaluation of familial aggregation, vegetable consumption, legumes consumption, and physical activity on functional constipation in families of children with functional constipation versus children without constipation

Introduction Constipation is a frequent complication in paediatrics. Most of the constipation is functional. Functional constipation constitutes 25% of visits in paediatric gastroenterology clinics. Two studies were published regarding aggregation or clustering of functional constipation. Only one of these research projects was about a paediatric population. Aim To elucidate the cluster pattern of constipation among the families of children with constipation. Material and methods This case-control study was carried out on the families of 37 children < 18 years old with chronic functional constipation and the families of 37 healthy children as controls. Cases were enrolled in the study according to Rome III criteria for constipation. The control group was selected from children < 18 years old who visited the well baby clinic of the university. Parents and siblings were evaluated regarding constipation. Rome II and III were used for evaluation of constipation for adults and children, respectively. Data was analysed using SPSS (Chicago, IL, USA). The χ2 and t-test were used for comparison. Results Physical activity and vegetable consumption were seen more frequently in the control group compared to the cases, but these differences were statistically insignificant. Constipation in mothers was significantly higher in the case group compared to the control group (p = 0.015). There was no significant difference between the two groups regarding exercise and vegetable consumption. Conclusions The frequency of constipation among mothers was significantly higher in the case group compared to the control group. Another study is recommended in a larger population for evaluation of genetic background, diet, physical activity, and familial clustering among mothers of children with constipation.

Association of Plasma Retinol Binding Protein-4 (RBP4) and Sonographic Grading of Fatty Liver in Obese Iranian Children

Background The prevalence of obesity and its related comorbidities, such as fatty liver, in children is increasing worldwide mostly due to changes in diet and life-style. Many serological markers have been suggested for screening of fatty liver but investigations for finding more reliable factors are still in progress. Objectives This study aimed to investigate the correlation between the level of retinol binding protein-4 (RBP4) in the serum and sonographic grading of fatty-liver severity in obese Iranian children. Patients and Methods This case-control, double-blind study involved 51 obese children aged between five and 17 years as the case group. In addition, 35 healthy lean children with no liver problems were selected as the control group. Plasma RBP4 (using an ELISA), serum triglycerides (TG), low-density-lipoproteins (LDL), high-density-lipoproteins (HDL), total-cholesterol (Chol), and body mass index (BMI) were measured. Grading the severity of the fatty liver condition was done by an expert radiologist in the case group. Results RBP4 levels in obese children (19 482.9 ± 3 302.2 pg/ml) were higher than those found in the lean control group (14 295.68 ± 2 381.3 pg/ml) (P < 0.05). In the obese patients, RBP4 levels showed a significant correlation with the grade of fatty liver and BMI (P < 0.05). Conclusions It was found that the level of RBP4 had a strong correlation with the severity of fatty liver. Therefore, RBP4 may be considered as a useful, noninvasive predictive biomarker of intrahepatic lipid content in obese children prior to using radiological investigations. In particular, abdominal sonography, for the evaluation of intrahepatic lipid content in obese patients, as the sensitivity of a sonography is decreased due to the increased thickness of the abdominal wall as a result of fat deposits.

Chemical Composition and the Effect of Walnut Hydrosol on Glycemic Control of Patients With Type 1 Diabetes.

Background Walnut hydrosol (WH) is used extensively by Iranian people with diabetes in order to control blood sugar (BS). There are few data regarding the effect of walnut on controlling diabetes. Objectives A pilot study to determine the efficacy and safety of WH in patients with type 1 diabetes. Materials and Methods Eight patients with diabetes mellitus (DM) type 1 were enrolled in the study. They did not use any medicine except insulin. They were advised to drink 250 mL WH after meals twice a day for four weeks. Their BS level was measured and their insulin dose was changed according to their BS. After four weeks, they discontinued WH use and their BS level was checked for two weeks. Descriptive statistics was used to analyze the data. Also, the essential oil of the sample was extracted using a liquid extractor and then analysis of the constituents was performed. Results The average daily BS level and insulin dose decreased in seven subjects. Two subjects developed generalized pruritic erythematous skin rash. One patient presented hypoglycemic coma. She had no other coma risk factor. Seven compounds were identified in the walnut essential oil and the rate of monoterpenoid and sesquiterpenes hydrocarbons were 53.45% and 5.95%, respectively. The main constituents of the oil were carvacrol (33.21%), thymol (16%) and homoveratrole (15.83%). Conclusions WH may control the glycemic level in people with diabetes, but it may be associated with minor and major side effects. Further in vitro studies, using these seven compounds, are recommended to determine the efficacy and complications of WH in people with diabetes.

The Outcome of Infantile Onset Pompe Disease in South of Iran

Background: Infantile Onset Pompe Disease (IOPD) is a rare autosomal recessive neuromuscular disorder. It is associated with cardiomegaly, hypotonia, paresis, and death in the first year of life. Since 2006, following the use of Alglucosidase alfa as Enzyme Replacement Therapy (ERT), the patients’ survival is improved to a noticeable extent. Objectives: The purpose of this study is to examine the outcome of IOPD patients in South of Iran and the degree of responsiveness to ERT. Patients and Methods: All patients who were diagnosed with IOPD on the bases of clinical symptoms, and enzyme assay on dried blood spot, were included in the study; and were followed up regarding cardiac function, locomotor activity, and cognition. Results: Six patients with IOPD were identified. All these six patients suffered from Hypertrophic Cardiomyopathy (HCM). Four (67%) of them also had generalized hypotonia. Three patients expired during the first weeks due to severe respiratory infection. One of them also got involved with Acute Cardiopulmonary Failure while receiving the fifth dose of ERT; and expired. However, the remaining two patients had a significant improvement after the maximum of 117 weeks of following up both cardiac and locomotor findings. These two patients were the same patients who showed cardiac symptoms from the beginning but did not have generalized hypotonia. Conclusions: Although ERT has a significant effect on enhancing the survival of IOPD patients, it should be associated with meticulous heart-respiratory cares during the first months of treatment and preventing infection especially nosocomial infections.

Stunting, wasting, and mid upper arm circumference status among children admitted to Nemazee Teaching Hospital

INTRODUCTION AND AIM The aim of this study was to evaluate nutritional status in children without prior hospital admission or evidence of chronic disease. SUBJECTS AND METHODS The current study is a cross-sectional and observational study which was conducted for assessing the nutritional status of children. In this study, consecutive sampling was used, with a sample size about 400 children aged 6 months to 18 years at first hospital admission. All subjects were hospitalized consecutively in the Pediatric Emergency Department of the Nemazee Teaching Hospital of Shiraz University of Medical Sciences (Shiraz, Islamic Republic of Iran). All children with evidence or history of chronic diseases such as liver cirrhosis, microcephaly, macrocephaly due to congenital infection or abnormal skull shape, patients with muscular or neurological problem, with prolonged steroid usage, nephrotic syndrome, cardiac problem, and protein loosing enteropathy were excluded from the study. The duration of the study was six months, starting from January 2016. RESULTS In the current study, 430 (225 boys and 175 girls) cases were included. Mean age was 5.39 (SEM 0.23) for boys and 5.78 (SEM 0.38) for girls. According to H/A criteria (current height/ideal height), 194 (48.5%) patients were stunted, 75 (18.8%) were mild, 49 (12.3%) were moderate and 70 (17.5%) were severe. According to W/A data (current weight/ideal weight), 188 (47%) of the patients studied were malnourished. Of these cases, 118 (29.5%) had mild malnutrition; 54 (13.5%), moderate; and 16 (4%), severe. According to body mass index (BMI), 40 (10%) patients were overweight, four (16%) were obese, and four (1%) were severe obese. In relation to middle upper arm circumference (MUAC), 56 (14%) patients were malnourished, 33 (8.3%) were at risk, 14 (3.5%) presented moderate malnutrition, and 9 (2.3%), severe malnutrition. CONCLUSION Prevalence of malnutrition among children without prior admission was 48.5% (according to H/A). According to W/A, 47% of children had different degrees of malnutrition.

Splicing defect in FKBP10 gene causes autosomal recessive osteogenesis imperfecta disease: a case report

BackgroundOsteogenesis imperfecta (OI) is a group of connective tissue disorder caused by mutations of genes involved in the production of collagen and its supporting proteins. Although the majority of reported OI variants are in COL1A1 and COL1A2 genes, recent reports have shown problems in other non-collagenous genes involved in the post translational modifications, folding and transport, transcription and proliferation of osteoblasts, bone mineralization, and cell signaling. Up to now, 17 types of OI have been reported in which types I to IV are the most frequent cases with autosomal dominant pattern of inheritance.Case PresentationHere we report an 8- year- old boy with OI who has had multiple fractures since birth and now he is wheelchair-dependent. To identify genetic cause of OI in our patient, whole exome sequencing (WES) was carried out and it revealed a novel deleterious homozygote splice acceptor site mutation (c.1257-2A > G, IVS7-2A > G) in FKBP10 gene in the patient. Then, the identified mutation was confirmed using Sanger sequencing in the proband as homozygous and in his parents as heterozygous, indicating its autosomal recessive pattern of inheritance. In addition, we performed RT-PCR on RNA transcripts originated from skin fibroblast of the proband to analyze the functional effect of the mutation on splicing pattern of FKBP10 gene and it showed skipping of the exon 8 of this gene. Moreover, Real-Time PCR was carried out to quantify the expression level of FKBP10 in the proband and his family members in which it revealed nearly the full decrease in the level of FKBP10 expression in the proband and around 75% decrease in its level in the carriers of the mutation, strongly suggesting the pathogenicity of the mutation.ConclusionsOur study identified, for the first time, a private pathogenic splice site mutation in FKBP10 gene and further prove the involvement of this gene in the rare cases of autosomal recessive OI type XI with distinguished clinical manifestations.

Oral Therapy in a Diabetic Patient With History of Infantile Hyperinsulinism.

Dear editor, Hyperinsulinism is the most common cause of persistent hypoglycemia in early infancy (1). Loss of function mutation in HNF4A gene is an unusual cause of this disease (2). HNF4A protein is a homodimer nuclear transcription factor with 474 amino acids which plays a role in 22 identified pathways. Mutations in this gene cause deficiency in regulation of beta-cell development and nuclear receptors transcription pathways, associated with maturity onset diabetes of Young (MODY) and HNF4A-related hyperinsulinism (3, 4). Association of hyperinsulinemia in infancy and diabetes in adolescence has been reported only in patients with HNF4A mutations (4). We present a patient with hyperinsulinmia in infancy and diabetes in adolescence without HNF4A mutation and with good response to oral hypoglycemic agents. In infancy, this patient presented with persistent hyperinsulinemic hypoglycemia. He was on oral diazoxide until 3 years of age when this drug was tapered and discontinued. Genetic study was not performed at that time due to limitation of facilities. After that time, his blood sugar was normal until 15 years of age when he presented with diabetes mellitus. Starting HbA1c was 9.5%. In addition, fasting triglyceride level and cholesterol level was 66 mg/dL and 168 mg/dL, respectively. Other routine laboratory studies were within the normal range. Pancreas anatomy was also normal in ultrasonography. At the time of manifestation of diabetes, he was 162 cm tall (about 25th percentile for sex and age) and 51 kg (about 25th percentile for sex and age). He did not have any family history of diabetes. Insulin therapy associated with oral sylfonylurea (Glibenclamid) was started with impression of monogenic diabetes. As he responded, insulin dose was gradually tapered and discontinued, and an α-glucodisase inhibitor (Acarbose) was started to improve his mild postprandial hyperglycemia. The treatment was continued with 0.1 mg/kg/day Glibenclamid and 50 mg Acarbose before each meal. Self-monitoring of blood glucose by the patient and most of the measurements were in the target range (70-130 mg/dL). After 4 months of treatment, HbA1c was 6.7%. He tolerated the medications well without any side effect. According to previous history of the patient, the most probable diagnosis was HNF4ɑ mutation. However, the results of HNF4ɑ gene study by DNA sequencing method revealed no mutation and only a previously reported variant rs745975 C > T determined in nucleotide 5 of intron 1 (5). This variant was associated with Stearoyl-CoA desaturase 1 activity (6) and with type 2 diabetes mellitus (7). History of hyperinsulinism in infancy, diabetes mellitus in adolescence, low plasma triglyceride level, and good response to oral hypoglycemic agents has been reported in previous cases of MODY type 1 with HNF4A mutation (8). Mutation in HNF4A was not found in the presented case and due to shortage of facilities, more genetic study was not performed, however, his clinical course is in favor of a type of monogenic diabetes. This case showed that some adolescent diabetic patients, even without family history of diabetes, and without clinical characteristics of type 2 diabetes may have good response to oral hypoglycemic agents. Further studies are needed to find more cases of monogenic diabetes in adolescents, and to determine which diabetic adolescent can be treated with oral agents. Also, it is recommended that in every patient whose diabetes commences in adolescence, a precise history about hypoglycemia of infancy should be obtained.