scholarly journals Novel TBC1D8B Variant in a 6-Month-Old Boy With Steroid-Sensitive Nephrotic Syndrome: A Case Report

2021 ◽  
Vol 9 ◽  
Author(s):  
Ling Hou ◽  
Lu Yin ◽  
Yubin Wu ◽  
Chengguang Zhao ◽  
Yue Du
Keyword(s):  
Nephrotic Syndrome ◽  
Age Of Onset ◽  
Pathogenic Variant ◽  
Structural Abnormality ◽  
Urine Protein ◽  
Steroid Resistant ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

A structural abnormality or dysfunction of podocytes is the major cause of nephrotic syndrome (NS). The TBC1D8B protein interacts with nephrin, a podocyte slit diaphragm protein, regulates vesicle transport, and functions in the pathogenesis of NS. We report a novel potentially pathogenic variant in the TBC1D8B gene in a 6-month-old boy with NS. A 6-month-old boy was admitted to the hospital because of edema and fever. Our systematic examination led to a diagnosis of NS. Because of the early age of onset, we performed trio whole-exome sequencing of him and his parents. The results showed a new potentially pathogenic variant in the TBC1D8B gene on the X chromosome, c.2717A>G (p.His906Arg). After routine glucocorticoid therapy, his urine protein turned negative, indicating steroid-sensitive NS. The new TBC1D8B variant identified here, c.2717A>G (p.His906Arg), may be associated with early-onset NS in children. Although NS due to pathogenic variants in this gene is more commonly steroid-resistant, our patient had steroid-sensitive NS.

scholarly journals Reverse Phenotyping after Whole-Exome Sequencing in Steroid-Resistant Nephrotic Syndrome

2019 ◽  
Vol 15 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Samuela Landini ◽  
Benedetta Mazzinghi ◽  
Francesca Becherucci ◽  
Marco Allinovi ◽  
Aldesia Provenzano ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Signs ◽  
Long Term Outcome ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Steroid Sensitive

Background and objectivesNephrotic syndrome is a typical presentation of genetic podocytopathies but occasionally other genetic nephropathies can present as clinically indistinguishable phenocopies. We hypothesized that extended genetic testing followed by reverse phenotyping would increase the diagnostic rate for these patients.Design, setting, participants, & measurementsAll patients diagnosed with nephrotic syndrome and referred to our center between 2000 and 2018 were assessed in this retrospective study. When indicated, whole-exome sequencing and in silico filtering of 298 genes related to CKD were combined with subsequent reverse phenotyping in patients and families. Pathogenic variants were defined according to current guidelines of the American College of Medical Genetics.ResultsA total of 111 patients (64 steroid-resistant and 47 steroid-sensitive) were included in the study. Not a single pathogenic variant was detected in the steroid-sensitive group. Overall, 30% (19 out of 64) of steroid-resistant patients had pathogenic variants in podocytopathy genes, whereas a substantial number of variants were identified in other genes, not commonly associated with isolated nephrotic syndrome. Reverse phenotyping, on the basis of a personalized diagnostic workflow, permitted to identify previously unrecognized clinical signs of an unexpected underlying genetic nephropathy in a further 28% (18 out of 64) of patients. These patients showed similar multidrug resistance, but different long-term outcome, when compared with genetic podocytopathies.ConclusionsReverse phenotyping increased the diagnostic accuracy in patients referred with the diagnosis of steroid-resistant nephrotic syndrome.

scholarly journals The role of cell signaling molecules in the pathogenesis of glomerulonephritis in children

2021 ◽  
Vol 64 (2) ◽  
pp. 37-41
Author(s):  
Angela Ciuntu ◽  
Keyword(s):  
Nephrotic Syndrome ◽  
Cell Signaling ◽  
Clinical Manifestations ◽  
Signaling Molecules ◽  
Control Group ◽  
Healthy Children ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

Background: Cytokines are functional class of tiny proteins and glycoprotein and fundamentally they are monomers that function as soluble mediators in an autocrine or paracrine manner. Cytokines are produced by a number of cell types, predominantly leukocytes, and their targets implicate both immune and non-immune cells. Material and methods: This study was performed on 75 children with glomerulonephritis (GN), aged from 2 up to 17 years. There were 20 children with steroid-sensitive nephrotic syndrome (SSNS), 15 children with steroid-resistant nephrotic syndrome (SRNS), 20 children with chronic glomerulonephritis (CGN) nephrotic form and 20 children with CGN mixed form. This study was performed on patients experiencing disease relapse and clinical remission. The control group consisted of 20 healthy children. Results: The results of this study demonstrated increased levels of cell signaling molecules (IL-8, TNF-α, MCP-1, MIP-1α) in the urine during clinical manifestations, valuable result due to their major role in the immunopathogenic mechanism of proteinuria in nephrotic syndrome. Conclusions: Determination of urinary concentrations of cellular signaling molecules may be useful as a predictive non-invasive method for estimating disease activity, monitoring disease progression, differentiating steroid-sensitive nephrotic syndrome from steroid-resistant nephrotic syndrome, and assessing the effectiveness of treatment in children with different variants of GN

scholarly journals Pediatric Patients With Steroid-Sensitive Nephrotic Syndrome Have Higher Expression of T Regulatory Lymphocytes in Comparison to Steroid-Resistant Disease

2019 ◽  
Vol 7 ◽  
Author(s):  
Fabio Tadeu Lourenço Guimarães ◽  
Rodrigo Novaes Ferreira ◽  
Gustavo Eustáquio Alvim Brito-Melo ◽  
Etel Rocha-Vieira ◽  
Wagner de Fátima Pereira ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Pediatric Patients ◽  
Steroid Resistant ◽  
Resistant Disease ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive ◽  
Regulatory Lymphocytes

A genetic study of steroid-resistant nephrotic syndrome: relationship between polymorphism -173 G to C in the MIF gene and serum level MIF in children

2015 ◽  
Vol 7 (1) ◽  
pp. 102-107 ◽  
Author(s):  
O. R. Ramayani ◽  
N. Sekarwana ◽  
P. P. Trihono ◽  
A. H. Sadewa ◽  
A. Lelo
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Children ◽  
Single Nucleotide ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Increased Risk ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

There is no satisfactory explanation as to why some nephrotic syndrome (NS) patients respond to glucocorticoids and others do not. The aim of this study was to investigate an association between single nucleotide polymorphism of the MIF gene -rs755622 and serum MIF concentrations in NS patients. During a period between November 2011 and September 2012, 120 consecutive children divided into three groups [healthy children, steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS)] were examined. Children were defined as healthy when they had a normal estimated glomerular filtration rate and spot urinary albumin creatinine ratio <150 μg/mg creatinine. SRNS was diagnosed in children who did not respond to the usual doses of steroids within 4 weeks of initiating treatment. SSNS patients were defined as those who had remission after usual doses of steroids. The genotype of -173 G to C polymorphism of the MIF gene was determined using polymerase chain reaction restriction fragment length polymorphism methods. Serum MIF concentration was measured using sandwich enzyme-linked immunosorbent assay. The allele frequency of the C allele was higher in SRNS compared with that of SSNS patients (P=0.025). There was a trend toward an association between genotypes and serum MIF disturbances. In conclusion, this study noted elevated circulating serum MIF levels and higher frequency of the C allele of the MIF gene in SRNS patients. The presence of the C allele implies an increased risk for steroid resistance.

scholarly journals Comparison of clinical and lab profile between steroid sensitive and steroid resistant nephrotic syndrome at onset of disease and evaluating predictors for developing steroid resistance in nephrotic syndrome

2020 ◽  
Vol 7 (6) ◽  
pp. 1304
Author(s):  
Anitha Palaniyandi ◽  
Subramani Palaniyandi
Keyword(s):  
Nephrotic Syndrome ◽  
Age At Onset ◽  
Steroid Resistance ◽  
First Episode ◽  
Observation Study ◽  
Serum Triglycerides ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

Background: Nephrotic syndrome is a notable chronic disease in children. The objective of this study was to compare the clinical and lab profile between steroid sensitive nephrotic syndrome and steroid resistant nephrotic syndrome at the onset of disease. Certain parameters were tested if they could be significate predictors of developing steroid resistance at the onset of first episode of nephrotic syndrome.Methods: Retrospective observation study done children 1-12 years diagnosed with nephrotic syndrome in Sri Ramachandra Medical College and Hospital, Department of Paediatrics, Chennai. Sample size 150. Period of study Jan 2013- Dec 2015. Variables considered were age at onset, sex, parental consanguinity with essential lab parameters done at the onset of nephrotic syndrome proteinuria, pyuria, microscopic hematuria, urine protein creatinine ratio, serum creatinine, serum triglycerides and serum albumin. Children less than 1 year of age, cases with secondary causes of nephrotic syndrome and steroid dependant nephrotic syndrome, children with incomplete records were not included in this study. 150 cases who fulfilled the study criteria were included in this study.Results: 75 cases of steroid sensitive nephrotic syndrome (SSNS) were compared with an equal number of steroid resistant nephrotic syndrome (SRNS). 85 children had onset of disease before 3 years of age and majority had 3+ proteinuria and males predominated in both the groups. The overall consanguinity rates were higher among SRNS group. Triglyceride level >300 mg/dl predominated in SRNS group along with a higher severity of hypoalbuminemia when compared to SSNS group. None of the parameters tested were significant predictors of developing SRNS subsequently.Conclusions: Comparing steroid sensitive with steroid resistance nephrotic syndrome, no lab parameter could identify the risk of a child developing steroid resistance subsequently. This could be a field of interest in future studies that could predict the development of steroid resistance at the onset of first episode of nephrotic syndrome itself. 

scholarly journals HUBUNGAN ASPEK KLINIS DAN LABORATORIUM DENGAN TIPE SINDROM NEFROTIK PADA ANAK

e-CliniC ◽  
2016 ◽  
Vol 4 (1) ◽  
Author(s):  
Robin Samuel Mamesah ◽  
Adrian Umboh ◽  
Stevanus Gunawan
Keyword(s):  
Blood Pressure ◽  
Nephrotic Syndrome ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Glomerular Diseases ◽  
Steroid Resistant ◽  
Cholesterol Levels ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive ◽  
The Relationship

Abstract: Nephrotic Syndrome (NS) is one of the most frequent glomerular diseases in children marked with proteinuria, hypoalbuminaemia, and edema with or without hypercholesterolemia. Approximately there are six cases of NS per year every 100.000 child aged less than 14 years old in Indonesia with ratio between males and females 2:1. Based on therapy, NS is categorized into Steroid Sensitive Nephrotic Syndrome (SSNS) and Steroid Resistant Nephrotic Syndrome (SRNS). This study aimed to obtain the relationship between clinical and laboratory aspects with NS type in children. This was a retrospective analytical study conducted by using SSNS and SRNS patient data of the medical record in Department of Pediatric Prof. Dr. R. D. Kandou Hospital Manado. Daya were categorized into identity, age, blood pressure, proteinuria, hematuria, as well as albumin and cholesterol levels. The results showed that there were 29 SN patients (18 patients of SSNS and 11 patients of SRNS) consisted of 17 males (59%) and 12 females (41%). The statistical analysis showed that there was no significant correlation among sex (p=0.064), age (p=0.064), edema (p=0.138), systolic pressure (0.283), diastolic pressure (p=0.701), proteinuria (p=0.999), hematuria (p=0.060), albumin (p=0.175), and cholesterol (p=0.814) in both of SSNS and SRNS patients. Conclusion: There was no relationship between sex, age, blood pressure, proteinuria, hematuria, albumin, and cholesterol related to SSNS and SRNS. Keywords: nephrotic syndrome, proteinuria, SSNS, SRNS Abstrak: Sindrom nefrotik (SN) adalah salah satu penyakit glomerulus yang sering ditemukan pada anak, yang ditandai dengan proteinuria, hipoalbuminemia, dan edema dengan atau tanpa hiperkolesterolemia. Diperkirakan enam kasus per tahun tiap 100.000 anak kurang dari 14 tahun di Indonesia dengan perbandingan antara laki-laki dan perempuan 2:1. Sindrom nefrotik berdasarkan respon terapinya terbagi menjadi sindrom nefrotik sensitif steroid (SNSS) dan sindrom nefrotik resisten steroid (SNRS). Penelitian ini bertujuan untuk mengetahui hubungan aspek klinis dan laboratorium dengan tipe SN pada anak. Jenis penelitian ini analitik retrospektif pada pasien SNSS dan SNRS berdasarkan data rekam medik di Bagian Ilmu Kesehatan Anak RSUP Prof. Dr. R. D. Kandou Manado. Data dikumpulkan meliputi identitas, usia, tekanan darah, proteinuria, edema, hematuria, hematuria, serta kadar albumin dan kolesterol. Hasil penelitian memperlihatkan 29 pasien SN terdiri dari 18 pasien SNSS dan 11 pasien SNRS. Laki-laki sebanyak 17 kasus (59%) dan perempuan 12 kasus (41%). Tidak didapatkan hubungan pada jenis kelamin (p=0,064), usia (p=0,064), edema (p=0,138), tekanan darah sistolik (p=0,283), tekanan darah diastolik (p=0,701), proteinuria (p=0,999), hematuria (p=0,060), albumin (p=0,175), kolesterol (p=0,814) pada kedua kelompok. Simpulan: Tidak terdapat hubungan antara jenis kelamin, usia, tekanan darah, proteinuria, hematuria albumin dan kolesterol dengan SNSS dan SNRS.Kata kunci: sindrom nefrotik, proteinuria, SNSS, SNRS.

scholarly journals R229Q Polymorphism of NPHS2 Gene in Group of Iraqi Children with Steroid-Resistant Nephrotic Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Shatha Hussain Ali ◽  
Rasha Kasim Mohammed ◽  
Hussein Ali Saheb ◽  
Ban A. Abdulmajeed
Keyword(s):  
Nephrotic Syndrome ◽  
Molecular Study ◽  
Control Group ◽  
Steroid Resistant ◽  
Sequence Variations ◽  
Medical City ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive ◽  
And Control ◽  
Nphs2 Gene

Background. The polymorphism R229Q is one of the most commonly reported podocin sequence variations among steroid-resistant nephrotic syndromes (SRNS). Aim of the Study. We investigated the frequency and risk of this polymorphism among a group of Iraqi children with SRNS and steroid-sensitive nephrotic syndrome (SSNS). Patients and Methods. A prospective case control study which was conducted in Al-Imamein Al-Kadhimein Medical City, spanning the period from the 1st of April 2015 to 30th of November 2015. Study sample consisted of 54 children having NS, divided into 2 groups: patients group consisted of 27 children with SRNS, and control group involved 27 children with SSNS. Both were screened by real time polymerase chain reaction for R229Q in exon 5 of NPHS2 gene. Results. Molecular study showed R229Q polymorphism in 96.3% of SRNS and 100% of SSNS. There were no phenotypic or histologic characteristics of patients bearing homozygous R229Q polymorphism and the patients with heterozygous R229Q polymorphism. Conclusion. Polymorphism R229Q of NPHS2 gene is prevalent in Iraqi children with SRNS and SSNS. Further study needs to be done, for other exons and polymorphism of NPHS2 gene in those patients.

scholarly journals Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome

2004 ◽  
Vol 66 (2) ◽  
pp. 564-570 ◽  
Author(s):  
Rainer G. Ruf ◽  
Michael Schultheiss ◽  
Anne Lichtenberger ◽  
Stephanie M. Karle ◽  
Isabella Zalewski ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Large Cohort ◽  
Steroid Resistant ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

scholarly journals Molecular factors predicting steroid resistance in pediatric nephrotic syndrome

2021 ◽  
pp. 32-37
Author(s):  
Ie. A. Burlaka ◽  
I. V. Bagdasarova
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistance ◽  
Control Group ◽  
Activation Markers ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Cellular Hypoxia ◽  
Steroid Sensitive ◽  
Nephrotic Children

Objectives: the objective of this paper was to study the levels of cellular hypoxia, apoptosis controlling factors in children with steroid-sensitive and steroid-resistant nephrotic syndrome. Background: patients with steroid-resistant nephrotic syndrome (SRNS) represent a challenging subset of patients with nephrotic syndrome who often fail standard immunosuppression and have a higher likelihood of progressing to end-stage renal disease. The search of the biochemical markers undergoing the steroid-resistance is under urgent need. Methods: an examination of kidney biopsies and blood of 56 patients (aged 10 to 15 years) with nephrotic syndrome was done. Conventional clinical investigations, immunohistochemistry, immunoblotting were used in this study. Results: patients with steroid-resistant nephrotic syndrome show an increased level of HIF-1 alfa (a marker of cellular hypoxia) as compared to the control group and children with steroid-sensitive nephrotic syndrome. Patients with steroid-resistant nephrotic syndrome show a down-regulation of anti-apoptotic marker BcL-xL as compared to the control group and children with steroid-sensitive nephrotic syndrome. Conclusion: hypoxia-induces disorders and apoptosis activation markers are considered to be included in the complex scheme predicting steroid-resistance in nephrotic children. 

Analysis of Predictors of Relapse in Children with Steroid Sensitive Nephrotic Syndrome

2017 ◽  
Vol 37 (1) ◽  
pp. 1-4
Author(s):  
Mukesh Bhatta ◽  
Gauri Shankar Shah ◽  
Om Prakash Mishra
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Therapy ◽  
Age Of Onset ◽  
Total Leukocyte Count ◽  
Late Response ◽  
Female Ratio ◽  
Younger Age ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive ◽  
One Year

Introduction: Children with idiopathic nephrotic syndrome (INS) are steroid responsive but have relapses in subsequent non-treatment period. The objective of the present study was to analyze the factors which could predict relapses in these children.Material and Methods: Forty patients of INS aged 1-14 years of both gender were enrolled over one year period and followed for six months after treatment of initial episode of Nephrotic Syndrome.Results: The median age of children was 4.5 years and male to female ratio 1.9:1. There were 24(60%) relapses and 16(40%) non-relapses. The relapses had significantly higher mean total leukocyte count, serum urea, potassium and cholesterol than non-relapses. It was also observed that the median age of onset in relapses was significantly lower than non-relapses (p<0.001). Also, the median time to response to steroid therapy was longer in relapses than non-relapses (p<0.001). Children who relapsed had infections at the time of relapse.Conclusion: Thus, onset of disease in younger age group, late response to steroid therapy and presence of infections were found to be associated with relapses in these children.

Sign in / Sign up

Export Citation Format

Share Document