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1.
Acta Clin Belg ; : 1-3, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31587616

RESUMO

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.

2.
Pediatr Int ; 61(12): 1250-1256, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31513327

RESUMO

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.

4.
Clin Rheumatol ; 38(7): 1947-1952, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30826945

RESUMO

OBJECTIVE: To explore the frequency of MEFV gene mutations in children with Henoch-Schönlein purpura who had no prior familial Mediterranean fever diagnosis and to evaluate the association of MEFV mutations with the clinical and laboratory features of Henoch-Schönlein purpura. METHODS: Data of 1120 patients diagnosed with Henoch-Schönlein purpura were reviewed retrospectively. The spectrum and degree of organ involvement and acute phase reactant levels were documented for each patient. Blood for MEFV gene mutation analysis was obtained either at the time of the Henoch-Schönlein purpura diagnosis or during follow-up visits. Pathological specimens of patients who underwent biopsy (renal/skin) were evaluated with special consideration for immunofluorescent examinations. RESULTS: Two hundred and thirty-eight (21.3%) patients were found to have one of the MEFV mutations in which exon 10 mutations were the most common (16.7%). Abdominal pain, joint involvement, scrotal involvement, and relapse were more frequent, and acute-phase reactant levels were significantly high in patients with MEFV mutations. More severe characteristics were observed in the presence of homozygous exon 10 mutations. There was no significant association between exon 2 variants and clinical course of Henoch-Schönlein purpura. Patients carrying MEFV mutations did not have significantly higher levels of IgA deposits in the biopsy materials. CONCLUSION: Henoch-Schönlein purpura in patients with homozygous exon 10 MEFV mutations seems to be more severe than that in patients carrying other mutations. In patients with exon 10 MEFV mutations, Henoch-Schönlein purpura might be considered as an associated presentation of familial Mediterranean fever rather than a separate clinical entity. Key points • p.M694V mutation is more common in Henoch-Schönlein purpura than in the general population. • p.E148Q variants have no impact on clinical symptoms and laboratory findings in Henoch-Schönlein purpura patients. • The majority of Henoch-Schönlein purpura patients with familial Mediterranean fever have no IgA deposits. • Henoch-Schönlein purpura in familial Mediterranean fever patients may be considered as an integral clinical feature of familial Mediterranean fever.


Assuntos
Mutação , Púrpura de Schoenlein-Henoch/genética , Púrpura de Schoenlein-Henoch/patologia , Pirina/genética , Adolescente , Proteína C-Reativa/análise , Criança , Pré-Escolar , Febre Familiar do Mediterrâneo/genética , Feminino , Homozigoto , Humanos , Masculino , Estudos Retrospectivos
5.
Clin Exp Nephrol ; 23(7): 939-947, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30895528

RESUMO

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
Nefropatias/patologia , Rim/patologia , Púrpura de Schoenlein-Henoch/patologia , Fatores Etários , Biópsia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Nefropatias/classificação , Nefropatias/tratamento farmacológico , Nefropatias/epidemiologia , Masculino , Púrpura de Schoenlein-Henoch/classificação , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Púrpura de Schoenlein-Henoch/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Turquia/epidemiologia
6.
Pediatr Int ; 61(3): 271-277, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30636381

RESUMO

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 , Turquia
7.
Pediatr Int ; 60(12): 1068-1072, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30320940

RESUMO

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 Retrospectivos
8.
Rheumatol Int ; 38(5): 879-885, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29450637

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/etiologia
9.
Pediatr Nephrol ; 33(6): 1099, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29380070

RESUMO

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.

10.
Pediatr Nephrol ; 33(5): 847-853, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29297098

RESUMO

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 Risco
11.
J Allergy Clin Immunol ; 142(1): 246-257, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29155101

RESUMO

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/patologia
12.
Mol Genet Metab ; 119(4): 311-316, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27915025

RESUMO

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 Jovem
13.
Clin Exp Rheumatol ; 34(6 Suppl 102): S115-S120, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27191192

RESUMO

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 , Turquia
14.
J Am Acad Dermatol ; 74(1): 186-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26584874

RESUMO

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/patologia
15.
Rheumatol Int ; 35(10): 1733-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26001859

RESUMO

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 Jovem
17.
J Hum Genet ; 60(1): 1-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25296579

RESUMO

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 , Turquia
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