scholarly journals MO142A SINGLE-CENTER CASE SERIES OF 150 PATIENTS WITH RENAL FANCONI SYNDROME

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Xiaoxiao Shi ◽  
Ying Wang ◽  
Jiaying Li ◽  
Zhixin Chen ◽  
Tiantian Ma ◽  
...  
Keyword(s):  
Fanconi Syndrome ◽  
Case Series ◽  
Pathological Features ◽  
Interstitial Edema ◽  
Renal Fanconi Syndrome ◽  
Female Ratio ◽  
Common Causes ◽  
Male Female Ratio ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

Abstract Background and Aims Renal Fanconi syndrome (RFS) is characterized by generalized dysfunctions of renal proximal tubular (PT) transport. The causes of FS can be inherited or acquired, the latter of which mostly includes drugs, heavy metals, monoclonal light chains (LC), and primary Sj gren’s syndrome (pSS). We intended to observe the clinico-pathological features of RFS with different etiologies. Method From January 2012 to September 2018, all the patients diagnosed as RFS in our hospital were enrolled. Their clinicopathological records were retrospectively reviewed. The diagnosis of RFS was defined as existence of ≥ 3 of the following five items alone or ≥ 2 items combined with an evidence of PT damages in kidney pathology: (I) normoglycemic glycosuria; (II) generalized aminoaciduria; (III) hypophosphatemia and hyperphosphaturia; (IV) hypouricemia and hyperuricosuria; (V) proximal RTA. Results: 1. Clinical characteristics We identified 150 RFS patients, with an average age of (45.9±14.2) years old and male: female ratio 1.3:1. They presented with different degrees of PT dysfunctions and the most common were hypophosphatemia (83.2%) and aminoaciduria (80.6%). Their mean eGFR levels were 76.3 (4.5-188.6) ml/min/1.73m2 with 73.5% had proteinuria. 2. Renal pathological features 47 RFS patients received kidney biopsy and the most common pathological diagnosis was interstitial nephritis. They all presented with different degrees of proximal tubule atrophy, defective brush border, interstitial edema and fibrosis. 3. Etiology-related clinicopathologic features The most common causes of our RFS were LC (14.0%), drugs (13.3%), and pSS (9.3%). Compared to pSS associated RFS, LC associated RFS patients showed a higher prevalence of bone involvement, more severe proteinuria and less severe hypokalemia (P < 0.05) despite similar eGFR levels. Specific renal pathological features were seen in different etiology groups, including crystalline formation and increased lysosomes in PT cells under electron microscope in LC associated RFS, and CD21 positive ectopic germinal center formation in renal interstitum in parts of the pSS associated RFS. Conclusion We identified 150 RFS with different etiologies and they showed etiology-specific patterns of PT dysfunctions and renal pathologic changes.

scholarly journals Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure

2018 ◽  
Vol 29 (7) ◽  
pp. 1849-1858 ◽  
Author(s):  
Markus Reichold ◽  
Enriko D. Klootwijk ◽  
Joerg Reinders ◽  
Edgar A. Otto ◽  
Mario Milani ◽  
...  
Keyword(s):  
Kidney Failure ◽  
Fanconi Syndrome ◽  
Genetic Disorder ◽  
Subsequent Development ◽  
Mitochondrial Morphology ◽  
Missense Mutations ◽  
Renal Fanconi Syndrome ◽  
Biopsy Specimens ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

Background For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure.Methods We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure. We performed genome-wide linkage analysis, sequencing, and expression studies in kidney biopsy specimens and renal cells along with knockout mouse studies and evaluations of mitochondrial morphology and function. Structural studies examined the effects of recognized mutations.Results The renal disease in these patients resulted from monoallelic mutations in the gene encoding glycine amidinotransferase (GATM), a renal proximal tubular enzyme in the creatine biosynthetic pathway that is otherwise associated with a recessive disorder of creatine deficiency. In silico analysis showed that the particular GATM mutations, identified in 28 members of the five families, create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells. GATM aggregates-containing mitochondria were elongated and associated with increased ROS production, activation of the NLRP3 inflammasome, enhanced expression of the profibrotic cytokine IL-18, and increased cell death.Conclusions In this novel genetic disorder, fully penetrant heterozygous missense mutations in GATM trigger intramitochondrial fibrillary deposition of GATM and lead to elongated and abnormal mitochondria. We speculate that this renal proximal tubular mitochondrial pathology initiates a response from the inflammasome, with subsequent development of kidney fibrosis.

Approach to the patient with renal Fanconi syndrome, glycosuria, or aminoaciduria

2018 ◽  
Author(s):  
Detlef Bockenhauer ◽  
Robert Kleta
Keyword(s):  
Fanconi Syndrome ◽  
Tubular Dysfunction ◽  
Renal Fanconi Syndrome ◽  
Renal Glycosuria ◽  
Proximal Tubular Dysfunction ◽  
Wide Range ◽  
Proximal Tubular ◽  
Proximal Tubular Function ◽  
Low Molecular Weight Proteins ◽  
Filtration Capacity

Up to 80% of filtered salt and water is returned back into the circulation in the proximal tubule. Several solutes, such as phosphate, glucose, low-molecular weight proteins, and amino acids are exclusively reabsorbed in this segment, so their appearance in urine is a sign of proximal tubular dysfunction. An entire orchestra of specialized apical and basolateral transporters, as well as paracellular molecules, mediate this reabsorption. Defects in proximal tubular function can be isolated (e.g. isolated renal glycosuria, aminoacidurias, or hypophosphataemic rickets) or generalized. In the latter case it is called the Fanconi–Debre–de Toni syndrome, based on the initial clinical descriptions. However, in clinical practice it is usually referred to as just the ‘renal Fanconi syndrome’. Severity of proximal tubular dysfunction can vary, and may coexist with some degree of loss of glomerular filtration capacity. Causes include a wide range of insults to proximal tubular cells, including a number of genetic conditions, drugs and poisons.

Adult Hemophagocytic Lymphohistiocytosis: Clinical Presentation and Follow-Up in a Consecutive Series of Ten Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3845-3845
Author(s):  
Keisuke Shirai ◽  
Alberto Montero ◽  
Jesse Powell ◽  
Lydia Christiansen ◽  
John Lazarchick
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Case Reports ◽  
Case Series ◽  
Hematologic Malignancies ◽  
Neurological Involvement ◽  
Consecutive Series ◽  
Female Ratio ◽  
Etoposide Treatment ◽  
Male Female Ratio ◽  
Underlying Causes

Abstract Hemophagocytic Lymphohistiocytosis (HLH) is very rare in adults but can be fatal without treatment. Reports in adults are limited to case reports and very small case series. Clinically it is characterized by fever, hepatosplenomegaly, lymphadenopathy, severe cytopenias, hepatic dysfunction, coagulopathy, as well as neurological involvement. This syndrome is associated with diverse processes including: infection, rheumatologic, and hematologic malignancies. Presently, the underlying cause of HLH is unknown. We present a cosecutive series of 10 adults with HLH diagnosed at our institution between 2004–2006. All diagnoses were confirmed by pathology. The median age was 59 years (range: 18–73 years), and a male: female ratio of 4:1. All patients uniformly presented with fever. Half of the patients presented with evidence of hepatomegaly or splenomegaly. The most predominant laboratory abnormalities included: leukopenia or thrombocytopenia (100%), and elevation of liver enzymes (50%). EBV IgG was positive in 8 of 10 patients. The underline illnesses associated with HLH were diverse. The underlying causes were as follows; acute leukemia (n=2), infection (n=2), rheumatologic (n=2), post transplant (n=2) sickle cell disease (n=2), unknown (n=2). Mortality rate was 60% with a median survival time since diagnosis of 58 days. One patient is still on maintenance cyclosporin after etoposide treatment. One patient is on steroid and cytoxan. One patient recovered just with supportive care. In conclusion, due to the high morality rate associated with HLH, early treatment with immunosuppressant is warranted and attempts to identify underlying cause.

Concurrent dural and perimedullary arteriovenous fistulas at the craniocervical junction: case series with special reference to angioarchitecture

2013 ◽  
Vol 118 (2) ◽  
pp. 451-459 ◽  
Author(s):  
Kenichi Sato ◽  
Toshiki Endo ◽  
Kuniyasu Niizuma ◽  
Miki Fujimura ◽  
Takashi Inoue ◽  
...  
Keyword(s):  
Case Series ◽  
Vascular Anomaly ◽  
Craniocervical Junction ◽  
Posterolateral Approach ◽  
Pathophysiological Mechanism ◽  
Arterial Aneurysm ◽  
Female Ratio ◽  
Arteriovenous Fistulas ◽  
Male Female Ratio ◽  
The Right

Object Dural arteriovenous fistulas (DAVFs) and perimedullary arteriovenous fistulas (PAVFs) are uncommonly associated in the craniocervical junction. The purpose of this study was to describe the clinical and angiographic characteristics of such concurrent lesions. Methods Authors reviewed 9 cases with a coexistent DAVF and PAVF at the craniocervical junction. Clinical presentation, angiographic characteristics, intraoperative findings, and treatment outcomes were assessed. Results All patients (male/female ratio 5:4; mean age 66.3 years) presented with subarachnoid hemorrhage. Angiography revealed that 8 patients had both a DAVF and PAVF on the same side, whereas 1 patient had 3 arteriovenous fistulas, 1 DAVF, and 1 PAVF on the right side and 1 DAVF on the left side. All of the fistulas shared dilated perimedullary veins (anterior spinal vein, 7 cases; anterolateral spinal vein, 2 cases) as a main drainage route. The shared drainage route was rostrally directed in 8 of 9 cases. Eight patients exhibited an arterial aneurysm on the distal side of the feeding arteries to the PAVF, and the aneurysm in each case was intraoperatively confirmed as a bleeding point. One patient had ruptured venous ectasia at the perimedullary fistulous point. All patients underwent direct surgery via a posterolateral approach. No recurrence was observed in the 4 patients who underwent postoperative angiography, and no rebleeding event was recorded among any of the 9 patients during the follow-up period (mean 38.4 months). Conclusions The similarity of the angioarchitecture and the close anatomical relationship between DAVF and PAVF at the craniocervical junction suggested that these lesions are pathogenetically linked. The pathophysiological mechanism and anatomical features of these lesions represent a unique vascular anomaly that should be recognized angiographically to plan a therapeutic strategy.

scholarly journals Clinical Heterogeneity and Phenotypic Expansion of NaPi-IIa–Associated Disease

2017 ◽  
Vol 102 (12) ◽  
pp. 4604-4614 ◽  
Author(s):  
Korcan Demir ◽  
Melek Yıldız ◽  
Hilla Bahat ◽  
Michael Goldman ◽  
Nisreen Hassan ◽  
...  
Keyword(s):  
Fanconi Syndrome ◽  
Loss Of Function ◽  
Renal Fanconi Syndrome ◽  
Whole Exome ◽  
Proximal Tubular ◽  
History Of ◽  
Proximal Tubulopathy ◽  
Idiopathic Infantile Hypercalcemia ◽  
Close Relatives

Abstract Context NaPi-IIa, encoded by SLC34A1, is a key phosphate transporter in the mammalian proximal tubule and plays a cardinal role in renal phosphate handling. NaPi-IIa impairment has been linked to various overlapping clinical syndromes, including hypophosphatemic nephrolithiasis with osteoporosis, renal Fanconi syndrome with chronic kidney disease, and, most recently, idiopathic infantile hypercalcemia and nephrocalcinosis. Objectives We studied the molecular basis of idiopathic infantile hypercalcemia with partial proximal tubulopathy in two apparently unrelated patients of Israeli and Turkish descent. Design Genetic analysis in two affected children and their close relatives was performed using whole-exome sequencing, followed by in vitro localization and trafficking analysis of mutant NaPi-IIa. Results Mutation and haplotype analyses in both patients revealed a previously described homozygous loss-of-function inserted duplication (p.I154_V160dup) in NaPi-IIa, which is inherited identical-by-descent from a common ancestor. The shared mutation was originally reported by our team in two adult siblings with renal Fanconi syndrome, hypophosphatemic bone disease, and progressive renal failure who are family members of one of the infants reported herein. In vitro localization assays and biochemical analysis of p.I154_V160dup and of additional NaPi-IIa mutants harboring a trafficking defect indicate aberrant retention at the endoplasmic reticulum in an immature and underglycosylated state, leading to premature proteasomal degradation. Conclusions Our findings expand the phenotypic spectrum of NaPi-IIa disruption, reinforce its link with proximal tubular impairment, enable longitudinal study of the natural history of the disease, and shed light on cellular pathways associated with loss of function and impaired trafficking of NaPi-IIa mutants.

scholarly journals Hypokalemia: A potentially life-threatening complication of tenofovir therapy

2017 ◽  
Vol 5 ◽  
pp. 2050313X1774101 ◽  
Author(s):  
Abhilash Koratala ◽  
Rupam Ruchi
Keyword(s):  
Cardiac Arrest ◽  
Fanconi Syndrome ◽  
Transcriptase Inhibitor ◽  
Tubular Dysfunction ◽  
Nucleotide Analog ◽  
Life Threatening ◽  
Proximal Tubular ◽  
Life Threatening Complication ◽  
Renal Proximal Tubular ◽  
Reverse Transcriptase Inhibitor

Tenofovir is a nucleotide analog reverse transcriptase inhibitor approved for the treatment of HIV and hepatitis B infections. It is widely prescribed and an integral part of the recommended regimens for the treatment of HIV infection in antiretroviral-naive patients. Tenofovir is implicated in renal proximal tubular dysfunction, which can be associated with Fanconi syndrome and hypokalemia. When the hypokalemia is severe, it can lead to life-threatening complications. We describe the case of a 59-year-old woman who suffered a cardiac arrest secondary to severe hypokalemia from tenofovir use.

FP122A Single-center Case Series of 25 Patients with Primary Sjӧgren’s Syndrome Associated Renal Fanconi Syndrome

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Xiaoxiao Shi ◽  
Zhixin Chen ◽  
Jing Wang ◽  
Yubing Wen ◽  
Linfeng Zou ◽  
...  
Keyword(s):  
Fanconi Syndrome ◽  
Case Series ◽  
Single Center ◽  
Renal Fanconi Syndrome ◽  
Primary Sjӧgren’S Syndrome

scholarly journals Endoscopic Profile of Children with Colorectal Polyps Attending a Tertiary Centre

2018 ◽  
Vol 37 (2) ◽  
pp. 134-137
Author(s):  
Satyam Upadhyay ◽  
Anna Sharma ◽  
Prabita Sapkota
Keyword(s):  
Colorectal Polyp ◽  
Colorectal Polyps ◽  
Therapeutic Modality ◽  
Female Ratio ◽  
Medical College ◽  
Tertiary Centre ◽  
Common Causes ◽  
Male Female Ratio ◽  
Rectal Mass ◽  
Gi Bleed

Introduction: Polyps are the most common causes of colorectal bleeding in children. This report describes an endoscopic profile of children with colorectal polyps at Nepal Medical College and Teaching Hospital.Materials and Methods: This prospective study was conducted in children who were evaluated for painless lower GI bleed who underwent colonoscopyin Nepal Medical College, Kathmandu, Nepal from November 2014 to May 2017. Patients with age of presentation less than or equal to 18 years and diagnosed endoscopically to have colorectal polyp were included in the study and were followed up till histopathological reports.Results:A total of 35children with colorectal polyps were identified. Twenty-three (65.7%) patients were males and 12 (35.3%) were females, male/ female ratio being 2.1: 1. The mean age of the patients at the time of diagnosis was 5.2 years (±3.7 years), (range 1.3-13.5) years. The duration of bleeding varied from 1 week to 3 years (mean 13 months), and 23 (67.6%) children were symptomatic for more than 12 months. All patients (100%) had painless rectal bleed, eight (23.5%) presented with anaemia and two of them requiring blood transfusion before the procedure (< 7.0 gm/dl),seven (20.5%) patients had blood and mucus in stools, six (17.6%) of them had rectal mass (prolapsed polyp).Conclusion:Juvenile colorectal polyps are the most common cause of painless rectal bleeding in young children. In the majority, these are solitary, occur in the rectosigmoid. Delay in treatment may cause anaemia.Colonoscopic snare polypectomy is a safe therapeutic modality.  

Aetiology of arthritis in hospitalised children: an observational study

2015 ◽  
Vol 100 (8) ◽  
pp. 742-747 ◽  
Author(s):  
Camille Aupiais ◽  
Brice Ilharreborde ◽  
Catherine Doit ◽  
Audrey Blachier ◽  
Marie Desmarest ◽  
...  
Keyword(s):  
Septic Arthritis ◽  
Tertiary Care ◽  
Case Series ◽  
First Episode ◽  
Tertiary Care Centre ◽  
Female Ratio ◽  
Fluid Analysis ◽  
Case Series Study ◽  
Male Female Ratio ◽  
Series Study

Background and objectiveArthritis in children has many causes and includes septic and viral arthritis, reactive arthritis and juvenile idiopathic arthritis (JIA). We aimed to describe the different types of arthritis among children hospitalised for a first episode of arthritis.DesignRetrospective, descriptive case series study.SettingA French tertiary care centre.PatientsChildren under 16 years of age hospitalised for an arthritis episode between 1 January 2008 and 31 December 2009.Main outcome measuresDemographic and clinical features were compared with χ2 or Fisher's exact tests and non-parametric tests.Results173 children were hospitalised for a first episode of arthritis during the study period, with a male/female ratio of 1.14. The most frequent cause of hospitalisation was septic arthritis (43.4% of cases, 69.3% of which were due to Kingella kingae and 10.7% to Staphylococcus aureus). JIA was responsible for 8.1% of cases and arthritis without any definitive diagnosis for 40.4%. Median age at diagnosis was 2.7 years (IQR 0.3–14.6) and was lower in the septic arthritis group (1.5 years; 1.1–3.4) than in the JIA group (4.7 years; 2.5–10.9) (p<0.01). Septic arthritis involved a single joint in 97.3% of cases, while JIA involved four joints in 14.3% of cases and two to four joints in 28.6% of cases (p<0.01).ConclusionsSeptic arthritis was the most frequent cause of arthritis in hospitalised children. Despite the increasing application of microbiological molecular methods to synovial fluid analysis, further measures are required to improve the diagnosis of arthritis of unknown cause.

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