Multiple sulfatase deficiency: A case series of four children

Multiple sulfatase deficiency is biochemically characterized by the accumulation of sulfated lipids and acid mucopolysaccharides. The gene sulfatase-modifying factor 1 (SUMF1), recently identified, encodes the enzyme responsible for post-translational modification of a cysteine residue, which is essential for the activity of sulfatases. We describe clinical findings and mutation analysis of four patients. The patients presented with hypotonia, developmental delay, coarse face, ichthyosis, and hepatosplenomegaly. The diagnosis was made through clinical findings, enzymatic assays, and mutation analysis. We were detected to be homozygous for a novel missense mutation c. 739G > C causing a p.G247R amino acid substitution in the SUMF1 protein.Key Words: Child, multiple sulfatase deficiency, sulfatase-modifying factor 1 gene     

Assessment of atherosclerosis risk due to the homocysteine–asymmetric dimethylarginine–nitric oxide cascade in children taking antiepileptic drugs

PurposeThe aim of this study was to assess the atherogenicity risk of antiepileptics in children by investigating the cascade, “hyperhomocysteinemia (HHcy) → asymmetric dimethylarginine (ADMA) increase → nitric oxide (NO) decrease”, which is thought to contribute to the developmental process of atherosclerosis.MethodsThe participants included 53 epilepsy patients who received either valproic acid (VPA, n = 26) or oxcarbazepine (OXC, n = 27). Twenty-four healthy sex- and age-matched children served as controls. Fasting plasma total homocysteine (tHcy), ADMA and NO levels were measured.ResultsThe differences in Hcy, ADMA, NO, vitamin B₁₂ and folate levels between VPA, OXC and control groups were all insignificant (p > 0.05 for all). In the patient group (VPA and OXC groups), 22.6% of the children (12/53) had tHcy levels above the normal cutoff (13.1 μmol/l) for children and 17% of the children (9/53) had tHcy levels of greater than 15 μmol/l which is accepted as the critical value for an increased atherosclerosis risk (p < 0.05 for both). The difference in rate of HHcy between VPA and OXC groups was statistically insignificant (p > 0.05, for both cut off levels of HHCy). There was a positive correlation of tHcy levels and antiepileptic drug treatment duration in the patient group (r = +0.276, p < 0.05).ConclusionHHcy may develop in patients using OXC. Contrary to some previous publications, our data do not suggest that OXC is safer than VPA in terms of HHcy risk. Further prospective, large scale and longer term studies investigating all suggested pathways responsible for development of atherosclerosis due to HHcy should be conducted to define the exact mechanism responsible for AEDs related atherosclerosis.     

Predicting alcohol dependence from multi-site brain structural measures

To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.     

The effect of alfuzosin on renal resistive index,urinary electrolytes and β2 microglobulin levels and TGF β-1 levels of kidney tissue in rats with unilateral ureteropelvic junction obstruction

Background: In this study, it was aimed to determine the effects of alfuzosin on experimentally generated unilateral partial ureteropelvic junction obstruction (UPO) in rats.

Materials and methods: Thirty Long–Evans rats were randomly allocated into five groups. In control group (C), nothing was performed; in group Sham (S) only laparotomy was done; in Alfuzosin group (A) only alfuzosin was administered for two weeks (10?mg/kg/day p.o.) without any surgery; in UPO group, unilateral UP junction obstruction was produced; and in the Group UPT (ureteropelvic obstruction?+?treatment), alfuzosin was administered for two weeks (10?mg/kg/day p.o.) in addition to UPO production. Renal pelvic anteroposterior diameters were determined with ultrasonography (USG) and renal arterial resistivity indexes by color Doppler USG. Urine was collected both at the beginning and at the end of the experiment for 24?h in all the groups and at the end of the experiment, blood samples were obtained. Blood and urine electrolytes and TGF-β1, urine density, urine β₂ microglobulin levels were determined. Renal tissue samples harvested from all of the rats were histopathologically evaluated. Results were determined using one-way ANOVA t-test; p?<?0.05 was accepted as significant.

Results: Urine density in the UPT group was lower with respect to UPO group and blood electrolytes were preserved as close to normal (p?<?0.05). In the UPT group, urine TGF-β1 and blood TGF-β1, blood β₂ microglobulin levels and histopathologic damage scores were lower compared to the UPO group (p?<?0.05).

Conclusion: It is shown in this experimental unilateral partial UPO model that alfuzosin treatment prevents obstructive renal damage.     

Increased serum renalase in hemodialysis patients: is it related to left ventricular hypertrophy?

Introduction: Left ventricular hypertrophy (LVH) is one of the most common cardiac abnormalities in patients with end stage renal disease (ESRD). Hypertension, diabetes, increased body mass index, gender, age, anemia, and hyperparathyroidism have been described as risk factors for LVH in patients on dialysis. However, there may be other risk factors which have not been described yet. Recent studies show that renalase is associated with cardiovascular events. The aim of this study was to reveal the relation between renalase, LVH in patients under hemodialysis (HD) treatment.

Methods: The study included 50?HD patients and 35 healthy controls. Serum renalase levels and left ventricle mass index (LVMI) were measured in all participants and the relation between these variables was examined.

Findings: LVMI was positively correlated with dialysis vintage and C-reactive protein (CRP) (r?=?0.387, p?=?0.005 and r?=?0.597, p?r?=??0.324, p?=?0.022 and r?=??0.499, p?r?=?0.263, p?=?0.065). Serum renalase levels were significantly higher in HD patients (212?±?127?ng/mL) compared to controls (116?±?67?ng/mL) (p?r?=?0.677, p?r?=?0.625, p?Discussion: In our study, LVMI was correlated with dialysis vintage, residual diuresis, CRP, and hemoglobin. LVMI tends to correlate with renalase and this correlation may be significant in studies with more patient numbers. The main parameters affecting renalase levels are dialysis vintage and serum creatinine.     

A new mutation identified in <Emphasis Type="Italic">SPATA16</Emphasis> in two globozoospermic patients

Purpose

The aim of this study is to identify potential genes involved in human globozoopsermia.

Methods

Nineteen globozoospermic patients (previously screened for DPY19L2 mutations with no causative mutation) were recruited in this study and screened for mutations in genes implicated in human globozoospermia SPATA16 and PICK1. Using the candidate gene approach and the determination of Spata16 partners by Glutathione S-transferase (GST) pull-down four genes were also selected and screened for mutations.

Results

We identified a novel mutation of SPATA16: deletion of 22.6 Kb encompassing the first coding exon in two unrelated Tunisian patients who presented the same deletion breakpoints. The two patients shared the same haplotype, suggesting a possible ancestral founder effect for this new deletion. Four genes were selected using the candidate gene approach and the GST pull-down (GOPC, PICK1, AGFG1 and IRGC) and were screened for mutation, but no variation was identified.

Conclusions

The present study confirms the pathogenicity of the SPATA16 mutations. The fact that no variation was detected in the coding sequence of AFGF1, GOPC, PICK1 and IRGC does not mean that they are not involved in human globozoospermia. A larger globozoospermic cohort must be studied in order to accelerate the process of identifying new genes involved in such phenotypes. Until sufficient numbers of patients have been screened, AFGF1, GOPC, PICK1 and IRGC should still be considered as candidate genes.

     

Role of the Neutrophil-Lymphocyte Ratio in the Differential Diagnosis of Exudative Pleural Effusion

OBJECTIVES:Pleural effusion is a common diagnostic and clinical problem. The differential diagnosis of pleural effusion may be difficult and may require several procedures, including invasive ones. Certain studies have investigated biochemical parameters to facilitate the diagnosis of exudative pleural effusion; however, it remains a challenging problem in clinical practice. We aimed to investigate the potential role of the neutrophil-lymphocyte ratio, which can be easily obtained by determining the cell count of the pleural fluid, in the differential diagnosis of exudative pleural effusion.METHODS:Records from patients who underwent thoracentesis and pleural fluid analysis between May 1, 2013, and March 1, 2015, were obtained from the electronic database of our hospital. The patients who met the inclusion criteria were divided into five groups according to their diagnosis: malignant pleural effusion, para-malignant pleural effusion, para-pneumonic effusion, tuberculosis-related effusion or other. The neutrophil-lymphocyte ratio value was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The patient groups were compared according to the given parameter.RESULTS:A total of 465 patients who met the inclusion criteria among 1616 patients with exudative pleural effusion were included in the study. The mean neutrophil-lymphocyte ratio value was significantly lower in tuberculosis-related pleural effusion compared to malignant, para-pneumonic and para-malignant effusions (p=0.001, p=0.001, p=0.012, respectively). The areas under the curve for tuberculosis pleurisy compared to malignant, para-pneumonic and para-malignant effusions were 0.38, 0.36, and 0.37, respectively. Lower cut-off values had higher sensitivity but lower specificity for tuberculosis pleurisy, while higher cut-off values had higher specificity but lower sensitivity for this condition.CONCLUSION:The pleural fluid neutrophil-lymphocyte ratio, which is an inexpensive, reproducible, and easily calculated hematological parameter, may facilitate the differential diagnosis of pleural effusion.