Wiedemann-Steiner Syndrome with a 2-Year Follow-Up

Wiedemann-Steiner syndrome (WDSTS) is an exceptionally rare genetic syndrome characterized by postnatal growth retardation, facial dysmorphism, hairy elbow, and short stature. It is known that the occurrence of WDSTS is due to mutations in KMT2A gene. It is noteworthy that not a great number of WDSTS have been identified yet; thereby, new phenotypes and features continue to be added. In this report, we describe a 5-year-old male patient presented with developmental delay, hypothyroidism, facial dysmorphism, and behavioral signs such as autistic spectrum features. By Whole Exome Sequencing (WES), a new mutation in KMT2A was found and WDSTS was diagnosed genetically. According to a genetic test, a variant in exon 27 of the KMT2A gene c.6647delT (p.Pro2215fs) was found. This mutation was not reported previously, also this case was the first WDSTS diagnosed in Iran. This syndrome is a rare genetic disorder representing a broad range of phenotypes. The mentioned low frequency emphasizes the importance of a phenotype-genotype correlation to be established. The phenotype comparison between our case and previously reported patient did not reveal any difference related to age or sex in patients with WDST

A Novel Heterozygous ACAN Variant in an Iranian Family with Short Stature: A Case Report

Background: Short stature is estimated to account for half of the new visits to pediatric endocrine practices. Therefore, evaluating its underlying causes seems essential in order to choose the best treatment. Recently, some studies revealed the impact of ACAN, which encodes for aggrecan, mutations on growth ranging from mild idiopathic short stature to severe skeletal dysplasia. Methods: Here, we describe clinical and molecular characteristics of an Iranian family with short stature using exome sequencing and co-segregation analysis through Sanger sequencing. Results: A novel variant of ACAN mutation c.1604delG (p.Arg535fs) was identified in the heterozygote pattern which was confirmed through co-segregation analysis in family members. Conclusion: We have found a novel variant within the ACAN gene in association with insignificant bone abnormality without a high incidence of familiar bone malformation. In order to achieve better clinical outcomes, we suggest genetic testing at an earlier age and also long-term GH treatment for children who are at risk of ACAN mutations. Children who are born small considering their gestational age, or who have persistent short stature, advanced bone age, midfacial hypoplasia, joint problems, or broad toes, can be candidates for ACAN sequencing

McCune-Albright Syndrome: A Case Report and Literature Review

McCune-Albright syndrome (MAS) is a rare, heterogenous, clinical condition caused by a rare genetic mutation. The disorder is more common in females and is characterized by a triad of cutaneous, bone and endocrine abnormalities.  We describe a girl patient with MAS having precocious puberty and multiple cafe-au-lait macules and deforming polyostotic fibrous dysplasia of bone. Clinical presentation and X-ray finding were strongly diagnostic for MAS, Patients with McCune-Albright syndrome reach the adult age with a significant burden of the disease that continuously reduces their quality of life. Skeletal deformities, fractures, hyperthyroidism, and hyperestrogenism are just few of the many challenges in the management of these patients. These disorders with close observation and early detection can be controlled

Association between microRNAs expression and signaling pathways of inflammatory markers in diabetic retinopathy

Diabetic retinopathy is one of the common and serious microvascular complications of diabetes mellitus, as hyperglycemia has metabolic effects on the retina. Hyperglycemia induces increased oxidative stress, which stimulates inflammation pathways and promotes vascular dysfunction of the retina that leads to increased capillary permeability and vascular leakage. One of the main factors involving diabetic retinopathy is the inflammation signaling pathways. In contemporary times, microRNAs (miRNAs) are identified as functional biomarkers for early detection and treatment of numerous diseases specifically diabetic retinopathy. MiRNAs can modulate gene expression through regulation of transcriptional and posttranscriptional of target genes. With that, miRNAs can regulate almost every cellular and developmental process, including the regulation of instinct immune responses and inflammation. The aim of this study is to investigate the role of miRNAs in inflammation pathways and the pathogenesis of diabetic retinopathy

Effects of Nigella sativa on glycemic control, lipid profiles, and biomarkers of inflammatory and oxidative stress: A systematic review and meta-analysis of randomized controlled clinical trials

The aim of this systematic review and meta-analysis was to evaluate the effects of Nigella sativa (N. sativa) on glycemic control, lipid profiles, and biomarkers of inflammatory and oxidative stress. Two independent authors systematically examined online databases consisting of, EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until October 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of the studied trials. The heterogeneity among the included studies were assessed using the Cochrane's Q test and I-square (I 2 ) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. A total of 50 trials were included in this meta-analysis. We found a significant reduction in total cholesterol (WMD: −16.80; 95% CI: −21.04, −12.55), triglycerides (WMD: −15.73; 95% CI: −20.77, −10.69), LDL-cholesterol (WMD: −18.45; 95% CI: −22.44, −14.94) and VLDL-cholesterol (WMD: −3.72; 95% CI: −7.27, −0.18) following supplementation with N. sativa. In addition, there was significant reductive effect observed with N. sativa on fasting glucose (WMD: −15.18; 95% CI: −19.82, −10.55) and HbA1C levels (WMD: −0.45; 95% CI: −0.66, −0.23). Effects of N. sativa on CRP (WMD: −3.61; 95% CI: −9.23, 2.01), TNF-α (WMD: −1.18; 95% CI: −3.23, 0.86), TAC (WMD: 0.31; 95% CI: 0.00, 0.63), and MDA levels (WMD: −0.95; 95% CI: −2.18, 0.27) were insignificant. This meta-analysis demonstrated the beneficial effects of N. sativa on fasting glucose, HbA1c, triglycerides, total-, VLDL-, LDLcholesterol levels

The effects of alpha-lipoic acid supplementation on inflammatory markers among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effect of alpha-lipoic acid (ALA) supplementation on the inflammatory markers among patients with metabolic syndrome (MetS) and related disorders. METHODS: We searched the following databases until November 2017: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Three reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies. Statistical heterogeneity was assessed using Cochran’s Q test and I-square (I2) statistic. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as the summary effect size. RESULTS: Eighteen trials out of 912 potential citations were found to be eligible for our meta-analysis. The findings indicated that ALA supplementation significantly decreased C-reactive protein (CRP) (SMD = − 1.52; 95% CI, − 2.25, − 0.80; P < 0.001), interlokin-6 (IL-6) (SMD = − 1.96; 95% CI, − 2.60, − 1.32; P < 0.001), and tumor necrosis factor alpha levels (TNF-α) (SMD = − 2.62; 95% CI, − 3.70, − 1.55; P < 0.001) in patients diagnosed with metabolic diseases. CONCLUSION: In summary, the current meta-analysis demonstrated the promising impact of ALA administration on decreasing inflammatory markers such as CRP, IL-6 and TNF-α among patients with MetS and related disorders

The effects of alpha-lipoic acid supplementation on inflammatory markers among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials

Abstract Objective This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effect of alpha-lipoic acid (ALA) supplementation on the inflammatory markers among patients with metabolic syndrome (MetS) and related disorders. Methods We searched the following databases until November 2017: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Three reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies. Statistical heterogeneity was assessed using Cochran’s Q test and I-square (I2) statistic. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as the summary effect size. Results Eighteen trials out of 912 potential citations were found to be eligible for our meta-analysis. The findings indicated that ALA supplementation significantly decreased C-reactive protein (CRP) (SMD = − 1.52; 95% CI, − 2.25, − 0.80; P < 0.001), interlokin-6 (IL-6) (SMD = − 1.96; 95% CI, − 2.60, − 1.32; P < 0.001), and tumor necrosis factor alpha levels (TNF-α) (SMD = − 2.62; 95% CI, − 3.70, − 1.55; P < 0.001) in patients diagnosed with metabolic diseases. Conclusion In summary, the current meta-analysis demonstrated the promising impact of ALA administration on decreasing inflammatory markers such as CRP, IL-6 and TNF-α among patients with MetS and related disorders

Additional file 3: of The effects of alpha-lipoic acid supplementation on inflammatory markers among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials

The effects of alpha-lipoic acid supplementation on inflammatory markers based on sensitivity analysis. (DOC 33 kb

Impact of Intravenous Trehalose Administration in Patients with Niemann–Pick Disease Types A and B

Background and aims: Niemann-Pick disease (NPD) types A (NPA) and B (NPB) are caused by deficiency of the acid sphingomyelinase enzyme, which is encoded by the SMPD1 gene, resulting in progressive pathogenic accumulation of lipids in tissues. Trehalose has been suggested as an autophagy inducer with therapeutic neuroprotective effects. We performed a single-arm, open-label pilot study to assess the potential efficacy of trehalose treatment in patients with NPA and NPB patients. ------ Methods: Five patients with NPD type A and B were enrolled in an open-label, single-arm clinical trial. Trehalose was administrated intravenously (IV) (15 g/week) for three months. The efficacy of trehalose in the management of clinical symptoms was evaluated in patients by assessing the quality of life, serum biomarkers, and high-resolution computed tomography (HRCT) of the lungs at the baseline and end of the interventional trial (day 0 and week 12). ----- Results: The mean of TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients after intervention at W12 compared to the baseline W0, although the difference was not statistically significant. The serum levels of lyso-SM-509 and lyso-SM were decreased in three and four patients out of five, respectively, compared with baseline. Elevated ALT and AST levels were decreased in all patients after 12 weeks of treatment; however, changes were not statistically significant. Pro-oxidant antioxidant balance (PAB) was also decreased and glutathione peroxidase (GPX) activity was increased in serum of patients at the end of the study. Imaging studies of spleen and lung HRCT showed improvement of symptoms in two patients. ----- Conclusions: Positive trends in health-related quality of life (HRQoL), serum biomarkers, and organomegaly were observed after 3 months of treatment with trehalose in patients with NPA and NPB. Although not statistically significant, due to the small number of patients enrolled, these results are encouraging and should be further explored