Cerebral Venous Sinus Thrombosis as an Initial Presentation of Nephrotic Syndrome: A Case Report.

Cerebral sinovenous thrombosis (CSVT) encompasses a spectrum of disorders involving thrombosis of the cerebral venous system. As shown by previous epidemiological studies, the prevalence of cerebral sinovenous thrombosis is 4-7 cases per million people. Nephrotic syndrome was very rarely associated with thrombosis cerebral veins or sinuses. Hypercoagulability and thrombotic complications in nephrotic syndrome are most commonly seen in deep veins of the lower extremities and renal veins. Our case highlights a unique scenario in which cerebral sinovenous thrombosis was the initial presentation of nephrotic syndrome in a patient that was not an important past medical or surgical problem. The patient was brought to the emergency department with severe headache, vomiting, altered mental status, and generalized body swelling. Laboratory results showed proteinuria, hypoalbuminemia and hyperlipidemia. Non-contrast brain CT demonstrated hemorrhagic venous infarct associated with vasogenic edema. A subsequent brain MR venogram demonstrated occlusion of superior sagittal and right transverse sinuses. She was managed with low molecular weight heparin and intervenous corticosteroids then shifted to rivaroxaban and oral steroids, respectively, which resulted in massive clinical improvement and resolution of thrombus.

Clinicopathological features and outcome of secondary steroid resistant nephrotic syndrome: A retrospective analysis.

Objective: To determine the clinico-pathological features and long-term outcome of secondary steroid-resistant nephrotic syndrome treated with steroids and calcineurin inhibitors. METHODS: The retrospective cohort study was conducted at the Sindh Institute of Urology and Transplant, Karachi, in June and July 2023, and comprised data from January 1, 2008, to December 31, 2020, of children aged 1-18 years who developed steroid resistance after initial sensitivity to steroids with at least 1-year of follow-up. Demographics as well as time taken to secondary steroid response were documented. Renal biopsy of all patients with secondary steroid resistance had been performed. Eventual outcomes after treatment with calcineurin inhibitors based on the degree of proteinuria and serum albumin levels were used to categorise complete remission, partial remission and no response. Kidney function, as determined by estimated glomerular filtration rate, was recorded. Data was analysed using SPSS 22. RESULTS: Of the 1,000 patients who underwent renal biopsy for steroid resistance, 48(4.8%) had idiopathic steroid-resistant nephrotic syndrome; 32(66.7%) males, 16(33.3%) females and median age of 5 years (interquartile range: 4-7.3 years). Median age at diagnosis of nephrotic syndrome was 5 years (interquartile range: 3.6-7.3 years). The median time from nephrotic syndrome to secondary steroid-resistant nephrotic syndrome was 23 months (interquartile range: 8.75-44.5 months). Biopsy results at diagnosis showed that 27(56.3%) had minimal change disease. The mean follow-up time was 6.1±3.2 years. Of the 43(89.5%) patients who received cyclosporin for 1 year, 29(67%) obtained complete remission, 5(12%) attained partial remission and no response was seen in 9(21%) patients. Conclusion: Majority of the children had minimal change disease at the time of diagnosis of secondary steroid-resistant nephrotic syndrome. The long-term response with calcineurin inhibitors was favourable at 1 year.

Immunoglobulin G4-related disease presenting with nephrotic syndrome due to minimal change disease: a case report.

BACKGROUND: Immunoglobulin G4-related disease is an inflammatory disease affecting multiple organs including the kidney. Immunoglobulin G4-related kidney disease most commonly manifests as a tubulointerstitial nephritis and is associated with glomerular disease in a proportion of cases. Membranous nephropathy is the most frequent glomerular lesion. Herein, we report the first documented case of immunoglobulin G4-related disease presenting with nephrotic syndrome owing to minimal change disease. CASE PRESENTATION: A 67-year-old South Asian male presented to our service with systemic upset and leg swelling. He had heavy proteinuria (urine protein:creatinine ratio 1042 mg/mmol) and was hypoalbuminemic (17 g/L) and hypercholersterolemic (9.3 mmol/L), consistent with the nephrotic syndrome. His serum creatinine was 140 µmol/L, and he was hypocomplementemic (C3 0.59 g/L, C4 < 0.02 g/L) with raised immunoglobulin G4 subclass levels (5.29 g/L). Kidney biopsy demonstrated minimal change disease alongside a plasma-cell-rich tubulointerstitial nephritis with strong positive staining for immunoglobulin G4. A diagnosis of minimal change disease in the setting of immunoglobulin G4-related disease was made. He was commenced on oral prednisolone at 60 mg daily but suffered infectious complications, including necrotizing fasciitis within 3 weeks of starting treatment, ultimately resulting in his death 52 days after initial presentation. CONCLUSION: This case highlights the potential for immunoglobulin G4-related disease to be associated with a spectrum of glomerular pathologies including minimal change disease. It adds to the differential diagnosis of secondary causes of minimal change disease, and moreover, aids as an important reminder of the potential complications of high-dose steroids used in its treatment.

[Steroid-Dependent Nephrotic Syndrome Due to Minimal Change Glomerulonephritis Treated with Rituximab].

47-year-old woman suffering from minimal lesion glomerulonephritis previously undergone high-dose steroid therapy and subjected to exacerbations of nephrotic syndrome after therapy discontinuation. It was decided to initiate off-label treatment with Rituximab at a dosage of 375 mg/m2 administred at zero-time, one-month and three months with good therapeutic response and resolution of the clinical laboratory picture. The therapy was well tolerated and had no side effects. This scheme could be an alternative to the conventional therapeutic scheme with steroids or other classes of immunosuppressive drugs, especially in order to avoid problems related to prolonged exposure to steroid therapy.

Implication of acute tubular injury in minimal change nephrotic syndrome.

While acute tubular injury (ATI) is known to occur in a significant number of minimal change disease (MCD) nephrotic syndrome cases with acute kidney injury (AKI), the clinical significance is not certain, and AKI may also occur without ATI. This study aimed to evaluate whether the severity of AKI defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria correlated with the presence or severity of ATI in a series of adult patients with MCD. We also looked at whether time to remission of nephrotic syndrome (NS) with treatment correlated with the presence of ATI in those with and without AKI. We excluded patients with secondary MCD. Of 61 patients, 20 had AKI (33%). ATI was significantly more likely to occur in those with AKI than in those without AKI (60 vs. 24%). Overall, the severity of AKI did not clearly correspond with the severity of ATI. Remission rates at 4 weeks were lowest (25%) in those with both AKI and ATI, while they were highest (100%) in those with neither AKI nor ATI. Patients with AKI but no ATI and those with no AKI but having ATI were intermediate in remission rates and similar to each other (60 and 62%, respectively). The time to remission in the group of those without AKI was significantly longer in those with ATI than in those without (p = 0.0027), but the numerical difference in remission did not reach statistical significance in the smaller group of AKI patients. Patients with ATI were older and more often male than those without ATI. It appears that having ATI may predict a slower remission rate in MCD though the reason for this is unclear. The different demographics of those with ATI may also play a role.

Choroidal Vascularity Index and Choroidal Structural Changes in Children With Nephrotic Syndrome.

Purpose: To investigate the choroidal vascularity index (CVI) and choroidal structural changes in children with nephrotic syndrome. Methods: This was a cross-sectional study involving 45 children with primary nephrotic syndrome and 40 normal controls. All participants underwent enhanced depth imaging-optical coherence tomography examinations. An automatic segmentation method based on deep learning was used to segment the choroidal vessels and stroma, and the choroidal volume (CV), vascular volume (VV), and CVI within a 4.5 mm diameter circular area centered around the macular fovea were obtained. Clinical data, including blood lipids, serum proteins, renal function, and renal injury indicators, were collected from the patients. Results: Compared with normal controls, children with nephrotic syndrome had a significant increase in CV (nephrotic syndrome: 4.132 ± 0.464 vs. normal controls: 3.873 ± 0.574; P = 0.024); no significant change in VV (nephrotic syndrome: 1.276 ± 0.173 vs. normal controls: 1.277 ± 0.165; P = 0.971); and a significant decrease in the CVI (nephrotic syndrome: 0.308 [range, 0.270-0.386] vs. normal controls: 0.330 [range, 0.288-0.387]; P < 0.001). In the correlation analysis, the CVI was positively correlated with serum total protein, serum albumin, serum prealbumin, ratio of serum albumin to globulin, and 24-hour urine volume and was negatively correlated with total cholesterol, low-density lipoprotein cholesterol, urinary protein concentration, and ratio of urinary transferrin to creatinine (all P < 0.05). Conclusions: The CVI is significantly reduced in children with nephrotic syndrome, and the decrease in the CVI parallels the severity of kidney disease, indicating choroidal involvement in the process of nephrotic syndrome. Translational Relevance: Our findings contribute to a deeper understanding of how nephrotic syndrome affects the choroid.

Nephrotic syndrome with rectus sheath hematoma: a case report.

BACKGROUND: Rectus sheath hematoma is a rare presentation often associated with abdominal trauma and anticoagulant therapy. Here, we present a patient with severe rectus sheath hematoma accompanied by nephrotic syndrome who achieved significant clinical improvement without the need for invasive treatment. CASE PRESENTATION: A 72-year-old Japanese woman was referred to our hospital for the treatment of nephrotic syndrome. She was receiving steroid and anticoagulant therapy. Then she had abdominal pain and she was diagnosed with spontaneous rectus sheath hematoma by abdominal computed tomography. She received transfusion and was managed conservatively with bed rest, which led to improvement in abdominal pain. CONCLUSION: Despite the absence of trauma history, rectus sheath hematoma should be considered in patients at risk of vascular failure, including those receiving anticoagulant or steroid therapy, those who are elderly, and those with nephrotic syndrome.

PLA2R-positive membranous nephropathy in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder associated with IgG4-RD, but membranous nephropathy is also seen in some cases. CASE PRESENTATION: Herein we report on the case of a 77-year-old male patient with nephrotic syndrome and IgG4-related lung disease. His serum phospholipase A2 receptor (PLA2R) antibody was positive. His renal biopsy specimen was also positive for PLA2R. The renal biopsy specimen showed membranous nephropathy with equal IgG3 and IgG4 immunofluorescence staining and no interstitial nephritis, suggesting IgG4-RD manifesting as membranous nephropathy. CONCLUSIONS: Nephrotic syndrome caused by membranous nephropathy is sometimes associated with IgG4-RD. In such cases, even if serum PLA2R antibody is positive, it should be considered that the membranous nephropathy may be secondary to IgG4-RD.

Thromboembolic phenomena in patients with nephrotic syndrome: pathophysiology, risk factors, prophylaxis and treatment.

Thromboembolic events resulting from disturbances in the body's balance of thrombotic and antithrombotic abilities are among the most life-threatening complications of nephrotic syndrome. Certain causes of nephrotic syndrome leave the patient particularly susceptible to thromboembolism. The severity of proteinuria and degree of hypoalbuminaemia are other common predictors of risk. Timely initiation of prophylactic therapy can help prevent morbidity and mortality associated with this complication in patients with nephrotic syndrome. The duration of treatment and choice of therapeutic agent depends on several factors, including the degree of hypoalbuminaemia, risk factors for thrombosis and risk of bleeding. This article reviews current understanding of the pathophysiology and risk factors for thromboembolism associated with nephrotic syndrome, and summarises recommendations and strategies for preventing and treating thromboembolic events in patients with nephrotic syndrome.

Risk factors and renal outcomes of AKI in children with secondary steroid-resistant nephrotic syndrome.

BACKGROUND: Acute kidney injury (AKI) is increasingly prevalent in children with nephrotic syndrome (NS). It is associated with adverse outcomes in NS, especially steroid-resistant nephrotic syndrome (SRNS). The incidence, risk factors and outcomes of AKI in secondary SRNS remain undefined. The main objectives of this study were to determine the risk factors and prognosis of AKI in hospitalized children with secondary SRNS. MATERIAL AND METHODS: This retrospective study was conducted from January 2014 to December 2019, involving 172 hospitalizations with secondary SRNS admitted to the First Affiliated Hospital of Sun Yat-sen University. AKI was defined and classified in accordance with the 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines. RESULTS: AKI was found in 67 (39.0%) of 172 hospitalizations with secondary SRNS. Average age of onset in our group is 4.4 (3.1, 6.7) years with AKI and 3.7 (1.8, 5.6) years without AKI. Urea nitrogen level is 5.9 (4.1, 10.0) mmol/L with AKI and 5.1 (3.7, 7.0) mmol/L. Uric acid level is 446.0 (340.0, 567.0) umol/L with AKI and 401.0 (303.0, 496.0) umol/L. 24-h urinary protein level is 4.14 (2.9, 6.5) g with AKI and 2.5 (1.3, 5.3) without AKI. Multivariate logistic regression revealed that infection (OR = 5.287; 95% confidence interval, 2.349 to 11.899; p < 0.001), age at onset (OR = 1.180; 95% confidence interval, 1.032 to 1.349; p = 0.015) and uric acid level (OR = 1.003; 95% confidence interval, 1.000 to 1.006; p = 0.031) were significantly associated with the development of AKI in children with secondary SRNS. Among 72 children with secondary SRNS, six went to end-stage kidney disease (ESKD). Children in the AKI group were more likely to progress to ESKD compared with children in the non-AKI group (p = 0.017) with a median follow-up of 48.5months. CONCLUSION: AKI occurred in 39.0% of total hospitalizations associated with secondary SRNS. Risk factors including infection, age of onset, and uric acid level are associated with AKI in children with secondary SRNS. Furthermore, AKI was identified as a risk factor for the progression of secondary SRNS to ESKD.

Hypothyroidism among Children with Nephrotic Syndrome Admitted to a Tertiary Care Centre.

Introduction: Nephrotic syndrome is a glomerular disease characterized by massive urinary protein loss occurring in children. Proteinuria also leads to loss of thyroid binding globulin affecting thyroid function. This study aimed to find out the prevalence of hypothyroidism among children with nephrotic syndrome admitted to a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among children with nephrotic syndrome admitted to a tertiary care centre from 06 July 2020 to 06 June 2021 after obtaining ethical approval from the Ethical Review Committee. They were tested for free T3, free T4 and TSH. A convenience sampling method was used. The point estimate was calculated at a 90% Confidence Interval. Results: Among 69 children with nephrotic syndrome, the prevalence of hypothyroidism was 49 (71.01%) (62.03-80.00, 90% Confidence Interval). Conclusions: The prevalence of hypothyroidism among children with nephrotic syndrome was higher than other studies done in similar settings. Keywords: children; hypothyroidism; nephrotic syndrome; prevalence.

Hypothyroidism among children and adolescents with nephrotic syndrome in Mulago National Referral Hospital, Kampala, Uganda; a cross-sectional study.

BACKGROUND: Nephrotic syndrome (NS) is the commonest glomerular disease among children. It is characterized by heavy proteinuria and is a risk factor for hypothyroidism in the affected children. Hypothyroidism is of concern because it affects the physical and intellectual development of children and adolescents. This study sought to establish the prevalence and factors associated with hypothyroidism among children and adolescents with NS. METHODS: A cross-sectional design was used to study 70 children and adolescents aged 1-19 years diagnosed with nephrotic syndrome and being followed up in the kidney clinic in Mulago National Referral Hospital. Questionnaires were used to collect patients' socio-demographics and clinical information. A blood sample was taken for analysis for thyroid stimulating hormone (TSH) and free thyroxine (FT4), renal function tests and serum albumin. Hypothyroidism included both overt and subclinical forms. Overt hypothyroidism was defined as TSH level > 10 mU/L and FT4 < 10pmol/L, or FT4 < 10pmol/l with normal TSH, or TSH < 0.5mU/l. Sub-clinical hypothyroidism was defined as TSH ranging between 5 and10 mU/L with normal age appropriate FT4 levels. Urine samples were collected and taken for a dipstick examination. The data was analyzed using STATA version 14. The Bayesian Logistic regression analysis approach was used to estimate odds ratios (OR) and their associated 95% credible intervals. All predictor variables with p value < 0.05 at frequentist statistical analysis were considered significant. RESULTS: The mean age (standard deviation) of participants was 9 years (3.8). There were more males; 36 of 70 (51.4%). The prevalence of hypothyroidism was 23% (16/70 participants). Of the 16 children with hypothyroidism, 3 (18.7%) had overt hypothyroidism while 13 had subclinical hypothyroidism. Only low serum albumin was found to be strongly associated with hypothyroidism; Bayesian OR 132.57 (CI 9.13-567.10) with a frequentist OR of 37 and a p value of 0.001. CONCLUSION: The prevalence of hypothyroidism among children and adolescent with nephrotic syndrome attending Mulago Hospital paediatric kidney clinic was 23%. Hypoalbuminemia was found to be associated with hypothyroidism. Therefore, children and adolescents that have severely low levels of serum albumin should be screened for hypothyroidism and linked to endocrinologists for care.

Nystagmus in a child with nephrotic syndrome.

We report a child with steroid-dependent nephrotic syndrome presenting with excessive irritability, double vision and inability to walk for 5 days. On examination, the child was irritable with Glasgow coma sccale (GCS of 12/15, had bilateral convergent squint (R>L), vertical nystagmus, ataxia without any focal neurological deficits and normal fundus. MRI brain with venogram showed bilateral symmetric FLAIR hyperintensity in the medial thalamus and periaqueductal grey matter showing diffuse restriction with normal venogram. A possibility of Wernicke encephalopathy (WE) was considered and the child was started on thiamine supplementation, following which he had significant improvement in his symptoms. His irritability reduced with significant improvement in the range of eye movements and vertical nystagmus. At 3-month follow-up, the child is asymptomatic with normal gait. Although WE is uncommon in children with nephrotic syndrome, the possibility has to be kept in mind when a child presents with atypical neurological symptoms.

Steroid induced ocular complications in idiopathic nephrotic syndrome: a cross sectional single center study.

Objective: To screen children receiving steroids to identify ocular complications and their prevalence. METHODS: The cross-sectional study was conducted at the Paediatric Nephrology and Ophthalmology departments of the Sindh Institute of Urology and Transplantation, Karachi, from May to October 2022, and comprised patients who received at least 1500mg cumulative steroid dose for a minimum of 3 months. They were screened for steroidsensitive or steroid-resistant nephrotic syndrome. Ocular examinations, including visual acuity, intraocular pressure, slit-lamp biomicroscopy, lens examination and fundus evaluation, were performed. Data was analysed using SPSS 22. RESULTS: Of the 124 subjects with mean age 8.15±2.03 years (range: 6-12 years), 64(51.6%) were boys. Steroidsensitive nephrotic syndrome was present in 97(78%) cases. The mean cumulative steroid dose was 3999.31±1564.22mg. Overall, 36(29%) children developed ocular complications. Blood pressure, number of relapses and the duration of treatment were significantly associated (p<0.05). Conclusion: Refractive errors were the most frequent side effects/complication seen among children with nephrotic syndrome who received prolonged corticosteroids.

Steroid-resistant minimal change nephrotic syndrome associated with thymoma treated effectively with rituximab following thymectomy and cyclosporine: a case report.

BACKGROUND: Minimal change nephrotic syndrome (MCNS) can be complicated by thymoma; however, no standard therapy for thymoma-associated MCNS has yet been established. We herein describe a case of steroid-resistant MCNS associated with thymoma, treated effectively with rituximab. CASE PRESENTATION: A 71-year-old Japanese man was referred to our department with severe proteinuria (20 g/gCr). Renal biopsy showed minimal change disease and computed tomography revealed an anterior mediastinal mass. Based on these findings, he was diagnosed with thymoma-associated MCNS. He was treated with oral prednisolone (50 mg/day) and cyclosporine, and underwent thymectomy and plasma exchange. However, no improvement in proteinuria was observed. He therefore received intravenous rituximab 500 mg, resulting in a marked decrease in proteinuria from 5328 to 336 mg/day after 1 week. CONCLUSIONS: This case suggests that rituximab might be an effective therapy in patients with steroid-resistant MCNS associated with thymoma.

Urokinase prophylactic anticoagulation in children with nephrotic syndrome: a multicenter retrospective cohort study.

OBJECTIVE: To analyze the clinical effect of urokinase on the prevention of thrombosis in children with primary nephrotic syndrome. METHODS: A total of 370 children diagnosed with primary nephrotic syndrome (PNS) in the Children's Hospital of Soochow University and Zibo Maternal and Child Health Hospital from January 2018 to December 2022 were selected as the research objects. The patients were divided into a urokinase adjuvant therapy group and non-urokinase adjuvant therapy group according to the application of drugs. The clinical data of the children were collected, including sex, age, drug application, bleeding during treatment, and telephone follow-up, to record whether thromboembolism occurred in the acute stage and remission stage. The clinical pattern of PNS, renal biopsy, histopathological type, and related laboratory indexes before and after treatment were recorded. RESULTS: A total of 313 patients were treated with urokinase and 57 patients were not. More thrombotic events was observed in non-urokinase group compared to the urokinase group(2 versus 0 episodes, p = 0.02). The thrombotic events observed included one patient had pulmonary embolism combined with right ventricular thrombosis, and another had intracranial venous thrombosis. More minor bleeding events occurred in urokinase group compared to the non-urokinase group(7 versus 1 episodes, p = 1.0). No major bleeding events occurred in either group. CONCLUSION: The rational prophylactic use of urokinase anticoagulation in children with PNS can prevent the formation of thromboembolism and has good safety.

Repeated implants failure in young patient with idiopathic nephrotic syndrome: a case report with brief review of the literature.

BACKGROUND: Nephrotic syndrome is a chronic disorder characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Idiopathic minimal-change disease is the most common form encountered in children. Corticosteroids are the cornerstone for the treatment of idiopathic nephrotic syndrome (INS), with different regimens depending on the response to therapy and frequency of relapses. This case report presents complications after implant treatment in patient with INS. CASE PRESENTATION: 20 years old female patient presented for implant consultation. Medical history includes INS since early childhood, and she is on different medications to control her condition, including long-term steroid use. Dental history revealed that implant treatment was unsuccessful after multiple attempts. She presented with an implant on the area of lower left first mandibular molar, that shows increased mobility and radiolucency on radiographic examination. A diagnosis of implant failure was made, the implant was removed, and the area was cleaned and sutured. The patient decided to replace her missing teeth with fixed partial denture and was referred for prosthodontist. The potential adverse effect of steroid use and the possible underlying mechanism that could affect bone metabolism and implants osseointegration are reviewed. CONCLUSION: Clinical practice guidelines are needed for the management of dental implants in chronic steroid users.

Neonatal nephrotic syndrome: all is not gloomy.

Congenital nephrotic syndrome (CNS) is a rare clinical syndrome with a constellation of proteinuria, hypoalbuminaemia and oedema, presenting within 3 months of birth. We present a rare case of neonatal nephrotic syndrome with a probable sepsis induced aetiology. The neonate was referred at day of life 15 with Klebsiella pneumonia sepsis and anasarca. On investigation, the patient had nephrotic range proteinuria, hypoalbuminaemia, generalised anasarca and ascites. The neonate was started on broad-spectrum antibiotics and furosemide. Genetic and other secondary causes of CNS were ruled out. With supportive management and resolution of sepsis, the neonate improved. This case highlights the rare cause of sepsis-induced nephrotic syndrome (NS), which required only supportive treatment without the need for aggressive management of CNS.

Loss of helicase C-terminal domain of SMARCAL1 protein associated with severe Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia (SIOD) is a rare multi-system condition caused by biallelic loss-of-function mutations in the SMARCAL1 gene. This disorder is characterized by disproportionate growth failure, T-cell deficiency, and renal dysfunction. Pathogenic variants in the SMARCAL1 gene have been reported in only approximately half of SIOD-affected individuals. Among these alterations, nonsense and frameshift mutations generally lead to a severe phenotype with early onset. In this study, we identified novel mutations in an Iranian patient with SIOD. A 4-year-old girl with developmental delay and facial dysmorphism was referred to our center for molecular diagnosis. We applied whole-exome and Sanger sequencing for co-segregation analysis. Subsequently, bioinformatic analysis was performed to assess the pathogenic effects of the variants and their post-transcriptional effects. We discovered two novel mutations (c.2281delT and c.2283delA) in exon 15 of the SMARCAL1 gene, resulting in a truncated protein with a loss of 193 amino acids (p.S761Rfs*1). Variant effect predictors indicated that these variants are pathogenic, and multi-sequence alignments revealed high conservation of this region among different species. Given that our patient exhibited severe a phenotype and passed away soon after receiving a definitive molecular diagnosis, we propose that the loss of the helicase C-terminal domain in the deleted part of SMARCAL1 may lead to the severe form of SIOD. Besides, the combination of growth retardation and bone abnormalities also plays a crucial role in the early diagnosis of the disease.

Nephrotic syndrome due to focal segmental glomerulosclerosis complicating scleroderma: a case report.

BACKGROUND: Systemic scleroderma (SSc) is an insidious autoimmune connective tissue disorder with multiorgan involvement. Renal involvement is one of the important causes of morbidity and mortality in scleroderma; however, nephrotic syndrome is reported rarely in association with SSc. We present a patient with SSc who developed focal segmental glomerulosclerosis (FSGS) as a complication of scleroderma. CASE PRESENTATION: A 59 year old Caucasian female patient, with a known history of diffuse systemic sclerosis from 8 years, presented to our clinic with symptoms of anasarca and weight gain. Her physical examination was unremarkable except for periorbital and extremity edema. Her biochemistry assessment revealed decreased serum albumin levels and elevated serum creatinine levels. A renal biopsy was performed, which showed histopathological patterns of FSGS type of nephrotic syndrome. After administration of high doses of steroid and rituximab in the course of her treatment for 6 months, her symptoms and proteinuria were improved without the occurrence of scleroderma renal crises. CONCLUSION: SSc is a complex multisystemic autoimmune disorder. SRC is the most prominent renal involvement in SSc, but other renal pathologies may also occur. Each patient should be precisely investigated since managing these renal conditions can differ significantly. Nephrotic syndrome is a rare complication of SSc, which could be managed with prompt diagnosis and steroid administration.