RESUMO
BACKGROUND: Children are one of the most vulnerable groups in conflict zones, especially those with chronic diseases. This study aimed to investigate kidney disease profiles and problems during follow-up in a population of Syrian refugee children residing in Turkey. METHODS: Syrian refugee children aged between 0 and 18 years were included in the study. Demographic data, diagnosis, particular interventions due to nephrological problems, and problems encountered during follow-up were obtained from all participating pediatric nephrology centers. RESULTS: Data from 633 children from 22 pediatric nephrology centers were included. Mean age of the children was 94.8 ± 61.7 months and 375 were male (59%). 57.7% had parental consanguinity and 23.3% had a close relative(s) with kidney disease. The most common kidney diseases were congenital anomalies of the kidney and urinary tract (CAKUT) (31.0%), glomerular disease (19.9%), chronic kidney disease (CKD) (14.8%), and urolithiasis (10.7%). Frequent reasons for CAKUT were nonobstructive hydronephrosis (23.0%), vesico-ureteral reflux (18.4%), and neurogenic bladder (15.8%). The most common etiology of glomerular diseases was nephrotic syndrome (69%). Ninety-four children had CKD, and 58 children were on chronic dialysis. Six children had kidney transplantation. Surgical intervention was performed on 111 patients. The language barrier, lack of medical records, and frequent disruptions in periodic follow-ups were the main problems noted. CONCLUSIONS: CAKUT, glomerular disease, and CKD were highly prevalent in Syrian refugee children. Knowing the frequency of chronic diseases and the problems encountered in refugees would facilitate better treatment options and preventive measures.
Assuntos
Refugiados , Insuficiência Renal Crônica , Adolescente , Criança , Pré-Escolar , Doença Crônica , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Insuficiência Renal Crônica/diagnóstico , Estudos Retrospectivos , Síria/epidemiologia , Anormalidades Urogenitais , Refluxo VesicoureteralRESUMO
BACKGROUND: Acute tubulointerstitial nephritis (ATIN) is a rare cause of acute kidney injury in children that can lead to chronic kidney disease. The aim of this study was to describe the presenting features, etiology, and clinical characteristics of childhood ATIN, and to evaluate treatment modalities and renal outcomes. METHODS: The study included 38 patients who had been diagnosed with ATIN, were younger than 18 years old, and were admitted for at least 6 months of follow up. RESULTS: The median age at diagnosis was 13.1 years (range 1.2-16.6 years). The female / male ratio was 1.37. The most common symptoms were abdominal pain (65.7%) and nausea / vomiting (55.2%). Twenty-three of the patients had a history of drug intake (60.5%), and the most active drugs in the etiology were non-steroidal anti-inflammatory drugs (56.5%). Eleven patients were given steroid therapy due to severe kidney involvement and rapid increases in serum creatinine values, and ten of those patients were drug-related ATIN cases. Other patients were given symptomatic treatment. Four patients needed several sessions of dialysis due to the severity of their acute renal failure. The follow-up creatinine and estimated glomerular filtration rate levels were not statistically different between the symptomatic and corticosteroid treated groups (P > 0.05). CONCLUSIONS: Although our study was unable to show the beneficial effect of corticosteroid therapy on the extent of renal recovery, the use of steroids may be preferable in severe nephritis because of the rapid recovery of estimated glomerular filtration rate with corticosteroid therapy.
Assuntos
Injúria Renal Aguda , Nefrite Intersticial , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Taxa de Filtração Glomerular , Humanos , Lactente , Rim , Masculino , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/etiologiaRESUMO
BACKGROUND: Alport syndrome (AS) is an inherited glomerular disease caused by mutations in COL4A3, COL4A4, or COL4A5. Associations between clinical manifestations and genotype are not yet well defined. Our study aimed to define clinical and genetic characteristics, establish genotype-phenotype correlations, and determine prognosis of AS in children. METHODS: A total of 87 children with AS from 10 pediatric nephrology centers, whom had genetic analyses performed at the Hacettepe University Nephrogenetics Laboratory between February 2017 and February 2019, were included. Data regarding demographics, family history, clinical and laboratory characteristics, histopathological and genetic test results, treatments, and yearly follow-up results were retrospectively analyzed. RESULTS: Of 87 patients, 16% presented with nephrotic syndrome. In patients with nephrotic syndrome, kidney biopsy findings showed focal segmental glomerulosclerosis (FSGS) in 79%, and COL4A3 mutations were the leading genetic abnormality (50%). Twenty-four percent of all patients progressed to chronic kidney disease (CKD). The rate of progression to CKD and the decline in the glomerular filtration rate of the patients with COL4A3 mutation were higher than other mutation groups (p < 0.001 and p = 0.04, respectively). In kidney survival analysis, nephrotic syndrome presentation, histopathology of FSGS, COL4A3 mutations, and autosomal recessive inheritance were found as independent risk factors for earlier progression to CKD. Cyclosporin A treatment did not improve kidney survival. CONCLUSIONS: We emphasize that genetic testing is important for patients suspected as having AS. Furthermore, COL4A mutations should be considered in patients with FSGS and steroid-resistant nephrotic syndrome. This approach will shed light on the prognosis of patients and help with definitive diagnosis, preventing unnecessary and potentially harmful medications. Graphical abstract.
Assuntos
Autoantígenos/genética , Colágeno Tipo IV/genética , Glomerulosclerose Segmentar e Focal/epidemiologia , Rim/patologia , Nefrite Hereditária/genética , Insuficiência Renal Crônica/epidemiologia , Adolescente , Biópsia , Criança , Pré-Escolar , Análise Mutacional de DNA , Progressão da Doença , Feminino , Seguimentos , Estudos de Associação Genética , Testes Genéticos , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Masculino , Mutação , Nefrite Hereditária/complicações , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/patologia , Prognóstico , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood. The long-term prognosis is variable and depends on renal involvement. The aims of this study were to investigate the clinical and laboratory characteristics of our HSP patients, to identify the risk factors for the development of Henoch-Schönlein purpura nephritis (HSPN) and to assess the efficacy of the Oxford Classification system for predicting renal outcomes. METHODS: We performed a retrospective review of HSP patients who admitted to our center between 2001 and 2016, and were < 18 years on admission. RESULTS: A total of 1120 children with HSP were analyzed. Their mean age was 7.4 ± 3.4 years. At onset, purpura was present in all cases, arthritis/arthralgia in 42.4%, abdominal involvement in 39% and renal involvement in 37%. Risk factors for the development of nephritis were age ≥ 8 years, atypical distribution of purpura, ESR > 20 mm/h and abdominal pain. Renal biopsy was performed on 75 patients before immunosuppressive treatment. The mesangial score was strongly associated with proteinuria. Segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and crescent formation of ≥ 50% were associated with reduced eGFR at the time of biopsy. A Kaplan-Meier plot showed that segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis significantly predict poor renal outcome. CONCLUSION: The long-term morbidity of HSP is predominantly attributed to renal involvement. Patients with HSP, who have a high risk to develop nephritis, could be followed for longer periods of time. The Oxford classification is useful in predicting long-term outcomes of HSPN.
Assuntos
Vasculite por IgA/patologia , Nefropatias/patologia , Rim/patologia , Fatores Etários , Biópsia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Vasculite por IgA/classificação , Vasculite por IgA/tratamento farmacológico , Vasculite por IgA/epidemiologia , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Nefropatias/classificação , Nefropatias/tratamento farmacológico , Nefropatias/epidemiologia , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Turquia/epidemiologiaRESUMO
BACKGROUND: CD80 (also known as B7-1) is a co-stimulatory molecule that is expressed in biopsies and also excreted in urine in patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). CD80 is inhibited by the cytotoxic T-lymphocyte-associated-antigen 4 (CTLA4), which is mainly expressed on regulatory T cells (Tregs). Ineffective circulating Treg response is involved in the pathogenesis of nephrotic syndrome. In this study, we evaluated CD80 expression and infiltrating Tregs in children with MCD and FSGS. METHODS: Evaluation of CD80 expression and semi-quantitative evaluation of Tregs (FOXP3-positive CD4 T cells) were carried out in 31 kidney biopsies (12 MCD, 19 FSGS) with immunofluorescence and immunohistochemistry staining. RESULTS: All MCD sections were stained negative; whereas six out of 19 FSGS sections (all from steroid-resistant (SR) patients), including one from a Wilms' tumor 1 (WT1) mutation-positive FSGS patient, stained positive for anti-CD80 goat antibody, and negative for anti-CD80 rabbit antibody. FSGS biopsy specimens had significantly higher FOXP3-positive cells/mm2 compared with MCD and control samples (P < 0.001). Biopsy samples from SR-FSGS patients (n = 12) with positive CD80 staining (n = 6) had significantly less Tregs (FOXP3-positive CD4 T cells) compared with CD80 (-) biopsies (n = 6; P = 0.004). CONCLUSION: CD80 expression was not detected in the majority of the archival biopsy sections and the results were not consistent across the different antibodies. In the SR-FSGS sections, however, CD80-positive biopsies had decreased FOXP3-positive CD4 T cells, suggesting that a decreased anti-inflammatory milieu may be the cause of increased CD80 expression.
Assuntos
Antígeno B7-1/metabolismo , Glomerulosclerose Segmentar e Focal/metabolismo , Nefrose Lipoide/metabolismo , Síndrome Nefrótica/metabolismo , Linfócitos T Reguladores/metabolismo , Adolescente , Biópsia , Antígeno CTLA-4/metabolismo , Criança , Pré-Escolar , Imunofluorescência , Fatores de Transcrição Forkhead/metabolismo , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Imuno-Histoquímica , Rim/metabolismo , Rim/patologia , Nefrose Lipoide/patologia , Síndrome Nefrótica/patologiaRESUMO
BACKGROUND: The aim of this study was to identify the cut-offs of postnatal anteroposterior renal pelvic diameter (APRPD), according to the urinary tract dilation (UTD) classification system, to identify the predictors of final diagnosis of UTD and the need for surgery. METHODS: A total of 260 infants (336 renal units) with prenatally detected UTD were prospectively evaluated on serial ultrasonography by the same radiologist. Additional voiding cystourethrography and scintigraphy was done according to the clinical algorithm. RESULTS: Prenatal and postnatal APRPD in patients with transient dilation were significantly lower than in those with urinary tract anomalies (UTA). On follow up, the slope of decrease in APRPD was significantly higher in transient dilation compared with UTA. APRPD 10 mm at first-month ultrasonography, predicted UTA with a sensitivity of 83.1%, and specificity of 71.1%. On multivariate analysis the likelihood of surgical intervention and final diagnosis were predicted independently by the UTD system risk group. CONCLUSIONS: Careful ultrasonography evaluation can avoid unnecessary testing in patients with transient or clinically insignificant dilation. The UTD classification system is valid for evaluation of postnatal hydronephrosis and is reliable in predicting the need for surgical intervention.
Assuntos
Pelve Renal/diagnóstico por imagem , Ultrassonografia/métodos , Anormalidades Urogenitais/diagnóstico por imagem , Dilatação Patológica , Feminino , Humanos , Lactente , Recém-Nascido , Pelve Renal/anormalidades , Masculino , Gravidez , Estudos Prospectivos , Sensibilidade e Especificidade , TurquiaRESUMO
BACKGROUND: Pathological inflammatory syndromes of unknown etiology are commonly observed in ataxia telangiectasia (AT) and Artemis deficiency. Similar inflammatory manifestations also exist in patients with STING-associated vasculopathy in infancy (SAVI). OBJECTIVE: We sought to test the hypothesis that the inflammation-associated manifestations observed in patients with AT and Artemis deficiency stem from increased type I IFN signature leading to neutrophil-mediated pathological damage. METHODS: Cytokine/protein signatures were determined by ELISA, cytometric bead array, or quantitative PCR. Stat1 phosphorylation levels were determined by flow cytometry. DNA species accumulating in the cytosol of patients' cells were quantified microscopically and flow cytometrically. Propensity of isolated polymorhonuclear granulocytes to form neutrophil extracellular traps (NETs) was determined using fluorescence microscopy and picogreen assay. Neutrophil reactive oxygen species levels and mitochondrial stress were assayed using fluorogenic probes, microscopy, and flow cytometry. RESULTS: Type I and III IFN signatures were elevated in plasma and peripheral blood cells of patients with AT, Artemis deficiency, and SAVI. Chronic IFN production stemmed from the accumulation of DNA in the cytoplasm of AT and Artemis-deficient cells. Neutrophils isolated from patients spontaneously produced NETs and displayed indicators of oxidative and mitochondrial stress, supportive of their NETotic tendencies. A similar phenomenon was also observed in neutrophils from healthy controls exposed to patient plasma samples or exogeneous IFN-α. CONCLUSIONS: Type I IFN-mediated neutrophil activation and NET formation may contribute to inflammatory manifestations observed in patients with AT, Artemis deficiency, and SAVI. Thus, neutrophils represent a promising target to manage inflammatory syndromes in diseases with active type I IFN signature.
Assuntos
Ataxia Telangiectasia/imunologia , Armadilhas Extracelulares/imunologia , Síndromes de Imunodeficiência/imunologia , Interferon Tipo I/imunologia , Ataxia Telangiectasia/patologia , Proteínas de Ligação a DNA , Endonucleases/deficiência , Endonucleases/imunologia , Humanos , Síndromes de Imunodeficiência/genética , Proteínas de Membrana/genética , Ativação de Neutrófilo , Neutrófilos/imunologia , Neutrófilos/patologia , Proteínas Nucleares/deficiência , Proteínas Nucleares/imunologia , Vasculite/genética , Vasculite/imunologia , Vasculite/patologiaRESUMO
BACKGROUND: Thiol/disulphide homeostasis plays a critical role in numerous intracellular enzymatic pathways including antioxidant defense and detoxification. This study was designed to investigate the impact of thiol/disulfide homeostasis in adolescent patients with recently diagnosed primary hypertension (HT) using a novel and automated method. METHODS: Native thiol/disulphide levels were measured by a novel spectrophotometric method (Cobasc 501, Roche Diagnostics, Mannheim, Germany) in 30 patients with primary HT together with 30 healthy controls. RESULTS: The levels of native thiol, total thiol, and native thiol/total thiol ratios were significantly lower, while the disulphide level, disulphide/native thiol, and disulphide/total thiol ratios were significantly higher in patients with primary HT compared with the control group. There were significant positive correlations between 24-h mean systolic and diastolic blood pressure and disulphide levels, disulphide/native thiol, and disulphide/total thiol ratios. A multiple linear regression model showed that a disulphide/native thiol ratio above 5 and family history of HT are independent predictors of HT. CONCLUSIONS: Our study showed that dynamic thiol/disulphide homeostasis shifted towards disulphide formation in adolescent patients with primary HT. Understanding the role of thiol/disulfide homeostasis in primary HT might provide new therapeutic intervention strategies for patients.
Assuntos
Dissulfetos/sangue , Hipertensão Essencial/sangue , Homeostase/fisiologia , Compostos de Sulfidrila/sangue , Adolescente , Antioxidantes/metabolismo , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial/métodos , Estudos de Casos e Controles , Criança , Estudos Transversais , Ecocardiografia/métodos , Feminino , Humanos , Masculino , Estresse Oxidativo/fisiologia , Curva ROC , Fatores de RiscoRESUMO
Owing to an error in typesetting, the name of the author Atilla Halil Elhan was rendered wrongly. The original publication has now been corrected in this respect.
RESUMO
Familial Mediterranean fever (FMF), the most common hereditary autoinflammatory disorder is characterized by recurrent episodes of fever, serositis, arthritis. The major long-term result is amyloidosis. Colchicine remains the principle of the treatment; it not only prevents the acute attacks but also prevents the long-term complications such as amyloidosis; 5-10% of the patients are unresponsive to treatment. Recently new therapeutic options as anti-interleukin 1 agents are successfully used for the patients who do not respond to colchicine treatment. In this study, we retrospectively evaluated 11 pediatric colchicine-resistant FMF patients who were treated with canakinumab. Three of the patients had amyloidosis and two had uveitis. Based on our results, we suggest that canakinumab may be a safe and effective therapy in patients who are resistant to colchicine and even in the patients with amyloidosis. We also suggest that canakinumab might be a safe option for the patients with uveitis.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Adolescente , Fatores Etários , Amiloidose/etiologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Criança , Colchicina/uso terapêutico , Resistência a Medicamentos , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/diagnóstico , Humanos , Fatores Imunológicos/efeitos adversos , Insuficiência Renal Crônica/etiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Turquia , Uveíte/etiologiaRESUMO
BACKGROUND: Increased ultrasonography (US) use has been correlated with an increased incidence of pediatric renal cysts. For simple and stage II cysts, the malignancy risk is low in adulthood, no follow up is recommended; but there is no consensus on childhood management. Given that pediatric renal cysts may be manifestations of hereditary cystic diseases, a different approach and follow up should be taken for these patients. Herein we present the clinical characteristics and follow-up data of pediatric patients with simple and stage II renal cysts. METHODS: This cross-sectional study involved 57 children (mean age, 12.44 ± 3.65 years) with simple (n = 35) and stage II cysts (n = 22) who were diagnosed and followed at the present institution for ≥2 years. RESULTS: The median follow-up period was 2.84 years for simple and 3.10 years for stage II cysts. None of the patients developed complications. No change in cyst diameter was detected in 65.7% of simple or in 45.5% of stage II cysts, whereas 13 simple cysts (37.1%) and eight stage II cysts (36.4%) increased in diameter. The diameter change per year was significantly higher in the stage II cysts than in the simple cysts (P = 0.017). Overall, 13 patients (22%) had an estimated glomerular filtration rate <90 mL/min/1.73 m2 , and two patients had hypertension. CONCLUSION: Although the malignancy risk of simple and stage II kidney cysts is low for this age group, potential complications such as renal dysfunction, hypertension and hereditary cystic disease should be closely monitored.
Assuntos
Doenças Renais Císticas/patologia , Rim/patologia , Ultrassonografia/métodos , Adolescente , Criança , Estudos Transversais , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Doenças Renais Císticas/complicações , Doenças Renais Císticas/diagnóstico por imagem , Masculino , Nefrologia , Estudos RetrospectivosRESUMO
Primary hyperoxaluria type 1 (PH1) is a rare, autosomal recessive disease, caused by the defect of AGXT gene encoding hepatic peroxisomal alanine glyoxylateaminotransferase (AGT). This enzyme is responsible for the conversion of glyoxylate to glycine. The diagnosis of PH1 should be suspected in infants and children with nephrocalcinosis or nephrolithiasis. Early diagnosis and treatment is crucial in preventing disease progression to end stage kidney disease (ESKD). In this study, AGXT gene sequence analyses were performed in 82 patients who were clinically suspected (hyperoxaluria and nephrolithiasis or nephrocalcinosis with or without renal impairment) to have PH1. Disease causing mutations have been found in fifteen patients from thirteen families (18%). Novel mutations have been found (c.458T>A (p.L153X), c.733_734delAA (p.Lys245Valfs*11), c.52 C>T (p.L18F)) in three of 13 families. There were 3-year lag time between initial symptoms and the time of PH1 is suspected; additionally, 5.5-year lag time between initial symptoms and definitive diagnosis. Consanguinity was detected in 77% of the patients with mutation. After genetic diagnosis, one patient received combined kidney and liver transplantation. AGXT gene sequencing is now the choice of diagnosis of PH1 due to its non-invasive nature compared to liver enzyme assay. Early diagnosis and accurate treatment in PH1 is important for better patient outcomes.
Assuntos
Diagnóstico Precoce , Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/genética , Transaminases/genética , Adolescente , Adulto , Sequência de Bases/genética , Criança , Pré-Escolar , Consanguinidade , Éxons/genética , Feminino , Humanos , Hiperoxalúria Primária/fisiopatologia , Lactente , Masculino , Mutação , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to present the genetic and clinical data of the largest cohort of Turkish cryopyrin-associated periodic syndromes (CAPS) patients. METHODS: This is a two-centre descriptive study of Turkish children with clinical diagnosis of CAPS. NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. ASC dependent NF-κB activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. Disease activity and response to anti interleukin 1 (anti-IL-1) treatment was also assessed. RESULTS: Heterozygous germline NLRP3 mutation was detected in 8 of 14 enrolled patients (57.1%). Two novel somatic mutations Y560H and G307D were found which induced both THP-1 cell death and ASC dependent NF-kB activation. With anti-IL-1 treatment the disease activity was improved in all patients except one. Except two patients with macrophage activation syndrome (MAS) attack, there were no serious adverse events requiring hospitalisation. CONCLUSIONS: CAPS should be considered in all patients with typical symptoms even if Sanger-based genetic analysis is negative, since a considerable number of patients have mosaicism. Treatment should be patient-tailored and MAS should be considered as a rare complication.
Assuntos
Síndromes Periódicas Associadas à Criopirina/genética , Mutação , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Adolescente , Fatores Etários , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Proteínas Adaptadoras de Sinalização CARD , Linhagem Celular , Criança , Pré-Escolar , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Síndromes Periódicas Associadas à Criopirina/metabolismo , Proteínas do Citoesqueleto/metabolismo , Análise Mutacional de DNA , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Heterozigoto , Humanos , Imunossupressores/uso terapêutico , Síndrome de Ativação Macrofágica/genética , Masculino , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fenótipo , Fatores de Risco , Transfecção , Resultado do Tratamento , TurquiaRESUMO
Key teaching points ⢠SAVI is a recently described interferonopathy resulting from constitutive action of STING and up-regulation of IFN-ß signaling. ⢠SAVI is characterized by facial erythema with telangiectasia, acral/cold-sensitive tissue ulceration and amputations, and interstitial lung disease. It has overlapping features with Aicardi-Goutières syndrome and familial chilblain lupus. ⢠Traditional immunosuppressive medications and biologic therapies appear to be of limited benefit, but JAK inhibitors may impact disease progression.
Assuntos
Doenças Autoimunes/diagnóstico , Interferon Tipo I/genética , Doenças Pulmonares Intersticiais/diagnóstico , Dermatopatias Vasculares/diagnóstico , Anormalidades Múltiplas/diagnóstico , Adolescente , Doenças Autoimunes/genética , Progressão da Doença , Insuficiência de Crescimento , Dedos/patologia , Humanos , Doenças Pulmonares Intersticiais/genética , Masculino , Necrose/diagnóstico , Doenças Raras , Dermatopatias Vasculares/genética , Síndrome , Dedos do Pé/patologiaRESUMO
Alström syndrome (ALMS) is an autosomal recessive disease characterized by multiple organ involvement, including neurosensory vision and hearing loss, childhood obesity, diabetes mellitus, cardiomyopathy, hypogonadism, and pulmonary, hepatic, renal failure and systemic fibrosis. Alström Syndrome is caused by mutations in ALMS1, and ALMS1 protein is thought to have a role in microtubule organization, intraflagellar transport, endosome recycling and cell cycle regulation. Here, we report extensive phenotypic and genetic analysis of a large cohort of Turkish patients with ALMS. We evaluated 61 Turkish patients, including 11 previously reported, for both clinical spectrum and mutations in ALMS1. To reveal the molecular diagnosis of the patients, different approaches were used in combination, a cohort of patients were screened by the gene array to detect the common mutations in ALMS1 gene, then in patients having any of the common ALMS1 mutations were subjected to direct DNA sequencing or next-generation sequencing for the screening of mutations in all coding regions of the gene. In total, 20 distinct disease-causing nucleotide changes in ALMS1 have been identified, eight of which are novel, thereby increasing the reported ALMS1 mutations by 6% (8/120). Five disease-causing variants were identified in more than one kindred, but most of the alleles were unique to each single patient and identified only once (16/20). So far, 16 mutations identified were specific to the Turkish population, and four have also been reported in other ethnicities. In addition, 49 variants of uncertain pathogenicity were noted, and four of these were very rare and probably or likely deleterious according to in silico mutation prediction analyses. ALMS has a relatively high incidence in Turkey and the present study shows that the ALMS1 mutations are largely heterogeneous; thus, these data from a particular population may provide a unique source for the identification of additional mutations underlying Alström Syndrome and contribute to genotype-phenotype correlation studies.
Assuntos
Síndrome de Alstrom/genética , Consanguinidade , Estudos de Associação Genética , Adolescente , Síndrome de Alstrom/patologia , Proteínas de Ciclo Celular , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Mutação , Linhagem , Isoformas de Proteínas/genética , Proteínas/genética , TurquiaRESUMO
Familial Mediterranean fever (FMF) is the most common autoinflammatory disease worldwide. Approximately 5-10 % of patients are unresponsive to colchicine. Aim of this study was to determine the short- and long-term efficacy and safety of anti-interleukin 1 (anti-IL1) and anti-tumor necrosis factor agents in colchicine-resistant FMF cases in Turkish children and adolescents. This is a single-center retrospective case series of colchicine-resistant FMF patients. The included patients were treated with biologics for either colchicine resistance or because of one of the following: (1) amyloidosis, (2) recurrent prolonged febrile myalgia and frequent need of steroid and (3) persistent arthritis. Colchicine resistance was defined as at least one attack per month for three consecutive months and elevated erythrocyte sedimentation rate or C-reactive protein or serum amyloid A in-between attacks despite taking adequate dose of colchicine. Response to biologicals was evaluated by the Autoinflammatory Diseases Activity Index (AIDAI) score sheet, patients/parents'/physicians' global assessment of disease severity and laboratory parameters every 3-6 months. Fourteen patients were included in the study. Three patients were treated with etanercept for median 7 months (range 3-11 months), and all patients had to be switched to anti-IL1 treatment because of adverse effects and/or partial response. Eleven patients were treated with anakinra with a median duration of 8 months (4-60 months). Nine patients responded to treatment at the third month, but four of them switched to canakinumab because of noncompliance, local side effects and active arthritis. Nine patients were treated with canakinumab, all responded. At follow-up, in two patients the dose had to be increased, and on the other hand, in three patients the interval was increased to every 12-16 weeks. In three patients, anti-IL1 treatment could be stopped and they are fine with colchicine. This case series describes the largest cohort of colchicine-resistant FMF patients in childhood and adolescence. Anti-IL1 treatment is a safe and effective therapy to control inflammation. The treatment should be modified and decided for each patient on an individual basis.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Colchicina/uso terapêutico , Etanercepte/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Adolescente , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Criança , Pré-Escolar , Etanercepte/efeitos adversos , Febre Familiar do Mediterrâneo/diagnóstico , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Falha de Tratamento , Resultado do Tratamento , Adulto JovemAssuntos
Hipoprotrombinemias/sangue , Inibidor de Coagulação do Lúpus/sangue , Lúpus Eritematoso Sistêmico/sangue , Adolescente , Feminino , Humanos , Hipoprotrombinemias/complicações , Hipoprotrombinemias/diagnóstico , Hipoprotrombinemias/imunologia , Inibidor de Coagulação do Lúpus/imunologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Menorragia/etiologia , Menorragia/imunologia , SíndromeRESUMO
Congenital nephrotic syndrome (CNS) is a rare disorder characterized by massive proteinuria and marked edema manifesting in utero or during the first 3 months of life. CNS can be caused by congenital infections, allo-immune maternal disease or due to the genetic defects of podocyte proteins most commonly NPHS1. Here we present a case of Finnish-type congenital nephrotic syndrome along with feeding problems and abdominal distention which was diagnosed during follow-up as a gastric-duplication cyst with a novel mutation in the nephrin gene. CNS feeding problems are attributed mainly to primary disease but in literature there are case reports of patients with CNS and hypertrophic pyloric stenosis. NPHS1 is also expressed in the stomach tissue. Physicians should be aware of this rare extra-renal manifestation or coincidence of this rare disease.
Assuntos
Cistos , Síndrome Nefrótica , Finlândia , Humanos , Lactente , Rim , Proteínas de Membrana/genética , Mutação , Síndrome Nefrótica/complicações , Síndrome Nefrótica/genéticaRESUMO
Dent disease is a rare X-linked recessive tubular disorder, characterized by the triad of low molecular-weight proteinuria, hypercalciuria, nephrocalcinosis and/or nephrolithiasis. It is caused by mutations in the CLCN5 gene or OCRL gene. Thirty to 80% of affected males develop end-stage kidney disease between the ages of 30 and 50 years. Some children were reported to present with isolated persistent proteinuria and a part of these patients were diagnosed as having focal segmental glomerulosclerosis with kidney biopsy. Although there is no specific treatment, treatment of proteinuria and hypercalciuria is thought to delay the progression of the disease. For this reason, awareness of the disease findings and early diagnosis are important. In this case report, we present a boy followed-up with isolated persistent proteinuria and then diagnosed as having Dent disease with mutation analysis that showed c.328_330delT (p.Phe110Trpfs27*) in the CLCN5 gene. The importance of researching low-molecular- weight proteinuria and considering Dent disease in the differential diagnosis of children presenting with isolated persistent proteinuria has been emphasized.