Endocrinopathy complications and the role of serum ferritin as a marker of endocrinopathy prediction in patients with beta-thalassemia major

Background: This study aimed to estimate the prevalence of complications and in β-thalassemia patients, to identify its related risk factors and to determine the optimal thresholds of serum ferritin and disease duration as a predictor of the endocrine disease. Materials and Methods: A total of 140 patients with β-thalassemia major, 65 (46.4%) male with a mean age of 21.4 ± 7.5 (range 8–39) years were enrolled in this study. Logistic regression and receiver operating characteristic curve were used to estimate the diagnostic power of ferritin level and determine the optimal cut points. Results: The serum ferritin level was 3395 ± 2611 μg/L with stable trend across the last 5 years. Puberty delay was the most common complication with the prevalence of 33.6%. There was a significant association between ferritin levels and hypocalcaemia (odds ratio [OR] = 1.29, P = 0.001), short stature (OR = 1.04, P 2100 μg/L and >3400 μg/L optimal cut-off values of serum ferritin level for puberty delay was 2100 area under the curve (AUC = 0.78, P = 0.004) and 3400 for short stature (AUC = 0.74, P 1500 μg/L along with early second decade of illness is the best predictor for the development the endocrinopathy

Effect of Zinc Supplementation on Markers of Insulin Resistance, Oxidative Stress, and Inflammation among Prepubescent Children with Metabolic Syndrome

Objective: This trial aimed to evaluate the effects of zinc sulfate in comparison with placebo on markers of insulin resistance, oxidative stress, and inflammation in a sample of obese prepubescent children. Methods: This triple-masked, randomized, placebo-controlled, crossover trial was conducted among 60 obese Iranian children in 2008. Participants were randomly assigned to two groups of equal number; one group received 20 mg of elemental zinc and the other group received placebo on a regular daily basis for 8 weeks. After a 4-week washout period, the groups were crossed over. In addition to anthropometric measures and blood pressure, fasting plasma glucose, lipid profile, insulin, apolipoproteins A-1 (ApoA-I) and B, high-sensitivity C-reactive protein (hs-CRP), leptin, oxidized low-density lipoprotein (ox-LDL), and malondialdehyde were determined at all four stages of the study. Results: Irrespective of the order of receiving zinc and placebo, in both groups, significant decrease was documented for Apo B/ApoA-I ratio, ox-LDL, leptin and malondialdehyde, total and LDL-cholesterol after receiving zinc without significant change after receiving placebo. In groups, hs-CRP and markers of insulin resistance decreased significantly after receiving zinc, but increased after receiving placebo. In both groups, the mean body mass index (BMI) Z-score remained high, after receiving zinc, the mean weight, BMI, BMI Z-score decreased significantly, whereas these values increased after receiving placebo. Conclusion: These results are particularly important in light of the deleterious consequences of childhood obesity and early changes in markers of inflammatory and oxidative stress. We suggest exploring the direct clinical application of zinc supplementation in childhood obesity in future studies

Effect of Zinc Supplementation on Markers of Insulin Resistance, Oxidative Stress, and Inflammation Among Prepubescent Children with Metabolic Syndrome

Objective: This trial aimed to evaluate the effects of zinc sulfate in comparison with placebo on markers of insulin resistance, oxidative stress, and inflammation in a sample of obese prepubescent children. Methods: This triple-masked, randomized, placebo-controlled, crossover trial was conducted among 60 obese Iranian children in 2008. Participants were randomly assigned to two groups of equal number; one group received 20 mg of elemental zinc and the other group received placebo on a regular daily basis for 8 weeks. After a 4-week washout period, the groups were crossed over. In addition to anthropometric measures and blood pressure, fasting plasma glucose, lipid profile, insulin, apolipoproteins A-1 (ApoA-I) and B, high-sensitivity C-reactive protein (hs-CRP), leptin, oxidized low-density lipoprotein (ox-LDL), and malondialdehyde were determined at all four stages of the study. Results: Irrespective of the order of receiving zinc and placebo, in both groups, significant decrease was documented for Apo B/ApoA-I ratio, ox-LDL, leptin and malondialdehyde, total and LDL-cholesterol after receiving zinc without significant change after receiving placebo. In groups, hs-CRP and markers of insulin resistance decreased significantly after receiving zinc, but increased after receiving placebo. In both groups, the mean body mass index (BMI) Z-score remained high, after receiving zinc, the mean weight, BMI, BMI Z-score decreased significantly, whereas these values increased after receiving placebo. Conclusion: These results are particularly important in light of the deleterious consequences of childhood obesity and early changes in markers of inflammatory and oxidative stress. We suggest exploring the direct clinical application of zinc supplementation in childhood obesity in future studies

Identification of Two Novel Mutations in PKHD1 Gene from Two Families with Polycystic Kidney Disease by Whole Exome Sequencing

Background: Polycystic kidney disease (PKD) is an autosomal recessive disorder resulting from mutations in the PKHD1 gene on chromosome 6 (6p12), a large gene spanning 470 kb of genomic DNA. Objective: The aim of the present study was to report newly identified mutations in the PKHD1 gene in two Iranian families with PKD. Materials and Methods: Genetic alterations of a 3-month-old boy and a 27-year-old girl with PKD were evaluated using whole-exome sequencing. The PCR direct sequencing was performed to analyse the co-segregation of the variants with the disease in the family. Finally, the molecular function of the identified novel mutations was evaluated by in silico study. Results: In the 3 month-old boy, a novel homozygous frameshift mutation was detected in the PKHD1 gene, which can cause PKD. Moreover, we identified three novel heterozygous missense mutations in ATIC, VPS13B, and TP53RK genes. In the 27-year-old woman, with two recurrent abortions history and two infant mortalities at early weeks due to metabolic and/or renal disease, we detected a novel missense mutation on PKHD1 gene and a novel mutation in ETFDH gene. Conclusion: In general, we have identified two novel mutations in the PKHD1 gene. These molecular findings can help accurately correlate genotype and phenotype in families with such disease in order to reduce patient births through preoperative genetic diagnosis or better management of disorders. </jats:sec

Association of a novel homozygous mutation in the HMGCS2 gene with an HMGCSD in an Iranian patient

Abstract Background 3‐Hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) synthase 2 gene (HMGCS2) encodes a mitochondrial enzyme catalyzing the first reaction of ketogenesis metabolic pathway which provides lipid‐derived energy for various organs during times of carbohydrate deprivation, such as fasting. Mutations in this gene are responsible for HMG‐CoA synthase deficiency (HMGCSD). The aim of present study was to investigate the association of mutation in the HMGCS2 gene with HMGCSD in a patient with atypical symptoms. Methods The clinical and genetic features of an 8‐months‐old girl with HMGCSD were evaluated. Molecular genetic testing was conducted using whole‐exome sequencing (WES) in order to identify potential disease‐causing mutation. The WES finding was confirmed by the polymerase chain reaction (PCR) amplification of the target sequence carried out for the patient and her parents. The PCR products were subjected to direct sequencing using forward and reverse specific primers corresponding to the HMGCS2 gene. Results A novel homozygous missense mutation (c.266G>A p.Gly89Asp) was detected in the HMGCS2 gene. Sanger sequencing along with co‐segregation analysis of all family members confirmed this novel pathogenic germline mutation. The mutant gene was found to be pathogenic by bioinformatics analysis. Conclusion To our best knowledge, this is the first report of HMGCSD in Iran which would expand our knowledge about the mutational spectrum of the HMGCS2 gene and the phenotype variations of the disease