Zelal Ekinci

Loss-of-function mutations in WDR73 are responsible for microcephaly and steroid-resistant nephrotic syndrome: Galloway-Mowat syndrome.

Galloway-Mowat syndrome is a rare autosomal-recessive condition characterized by nephrotic syndrome associated with microcephaly and neurological impairment. Through a combination of autozygosity mapping and whole-exome sequencing, we identified WDR73 as a gene in which mutations cause Galloway-Mowat syndrome in two unrelated families. WDR73 encodes a WD40-repeat-containing protein of unknown function. Here, we show that WDR73 was present in the brain and kidney and was located diffusely in the cytoplasm during interphase but relocalized to spindle poles and astral microtubules during mitosis. Fibroblasts from one affected child and WDR73-depleted podocytes displayed abnormal nuclear morphology, low cell viability, and alterations of the microtubule network. These data suggest that WDR73 plays a crucial role in the maintenance of cell architecture and cell survival. Altogether, WDR73 mutations cause Galloway-Mowat syndrome in a particular subset of individuals presenting with late-onset nephrotic syndrome, postnatal microcephaly, severe intellectual disability, and homogenous brain MRI features. WDR73 is another example of a gene involved in a disease affecting both the kidney glomerulus and the CNS.

Urinary tract infection prophylaxis in children with neurogenic bladder with cranberry capsules: randomized controlled trial.

Objectives. The aim of this randomized controlled prospective study is to evaluate the efficacy of cranberry capsules for prevention of UTI in children with neurogenic bladder caused by myelomeningocele. Patients and Methods. To be eligible for this study, patients had to be diagnosed as neurogenic bladder caused by myelomeningocele, evaluated urodynamically, followed up with clean intermittent catheterization and anticholinergic drugs. Intervention. Six months of treatment with placebo; after a week of wash-out period treatment of cranberry extract tablets (1 capsule/day) for an additional 6 months. Randomization was performed sequentially. Patients and care givers were blinded to drug assignment. Main outcome measure was infection rate. Group comparisons were performed with Wilcoxon test. Results. The study population included 20 (F/M: 13/7) patients with neurogenic bladder with the mean age of 7.25 ± 3.49 (4, 18) years. The median UTI rate was 0.5/year during placebo usage whereas 0/year during cranberry capsule usage. Decrease in infection rate was significant with cranberry capsule usage (P = 0.012). Decrease in the percentage of the pyuria was also recorded as significant (P = 0.000). Any adverse events or side effects were not recorded. Conclusion. We concluded that cranberry capsules could be an encouraging option for the prevention of recurrent UTI in children with neurogenic bladder caused by myelomeningocele.

Effect of cholecalciferol on local arterial stiffness and endothelial dysfunction in children with chronic kidney disease

BackgroundAs cardiovascular factors are the leading cause of mortality in chronic kidney disease (CKD) and as vitamin D deficiency is prevalent in this population, we aimed to examine the effect of oral cholecalciferol on cardiac parameters and biomarkers for endothelial cell activation in children with CKD.MethodsForty-one children with CKD and 24 healthy subjects free of any underlying cardiac or renal disease with low 25-hydroxyvitamin D3 (25OHD) levels were evaluated using echocardiography basally and following Stoss vitamin D supplementation. The local vascular stiffness and endothelial dysfunction markers were compared among the groups.ResultsInitial flow-mediated dilatation (FMD) measurements were lower and local arterial stiffness was significantly higher in patients. After vitamin D supplementation, these improved significantly in patients, while no significant change was observed for the healthy group. Homocysteine showed inverse correlation with baseline vitamin D level in CKD children and von Willebrand factor emerged as an independent risk factor for FMD impairment.ConclusionsOur interventional study revealed the favorable effects of high-dose cholecalciferol on cardiovascular and endothelial parameters, implying the importance of vitamin D supplementation in children with CKD.

Childhood urinary tract infection caused by extended-spectrum β-lactamase-producing bacteria: Risk factors and empiric therapy.

This study investigated risk factors of childhood urinary tract infection (UTI) associated with extended‐spectrum β‐lactamase (ESBL)‐producing bacteria (ESBL‐positive UTI) and evaluated antimicrobial resistance as well as empiric treatment of childhood UTI.

Comparison of the efficacy of once- and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever – a randomized controlled noninferiority trial

BackgroundIn this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF).MethodsIn this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once- or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement.ResultsA total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once- and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group.ConclusionsUsing colchicine with either a once- or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage.Trial Registration IDClinicalTrials.gov identifier NCT02602028. Registered 5 November 2015.

Is neutrophil-to-lymphocyte ratio valid to predict organ involvement in Henoch–Schönlein purpura?

were assessed by Mann–Whitney U test. Receiver operating characteristic (ROC) curves were used to find out a cutoff value for predicting GI and/or renal involvement in HSP. The numbers and NLR median values with respect to the involvements of patients are shown in Fig. 1, and demographic and laboratory findings are summarized in Table 1. While no relationship between sex and organ involvement was detected, the age of group 1 was found significantly high. As shown in Table 1, statistically significant level of higher NLR was recorded in group 1 than in group 2. The area under the ROC curve (AUCROC) analysis showed that NLR could be a fair predictor of GI and/or renal involvement in HSP (AUCROC = 0.731, 95 % CI 0.66–0.79, p = 0.000). A cutoff NLR value was found as 3.09 for GI and/or renal involvement with 61 % sensitivity and 78 % specificity. With this retrospective study, it was revealed that high NLR level is related with GI and/or renal involvement in HSP. However, the role of NLR to foresee only renal involvement couldn’t be statistically evaluated due to very small number of patients (n = 2) who have only renal involvement. Makay et al. reported that high NLR might predict GI bleeding in HSP, and they suggested 2.82 as an optimal cutoff NLR value for predicting GI bleeding with 81 % sensitivity and 76 % specificity. But according to our hypothesis, establishing a relationship between NLR and disease severity is not a valid approach in HSP patients with GI bleeding since the cause of the increase in NLR level cannot be differentiated. It could be either raised from the inflammation or GI bleeding. Although the cutoff value obtained from our study group was not enough sensitive and specific to predict organ involvement, as the patients with GI bleeding were excluded, the results were assessed valuable. However, our study is limited by Dear Editor,

Early Bone Marrow Failure in a 6-Year-Old Boy with Cystinosis

With this letter we would like to share our experience to draw attention to the hematological symptoms of infantile cystinosis in a young boy. Patients with infantile cystinosis usually develop end-stage renal failure in the first decade if untreated [1]. Hematological symptoms, most with late onset, are reported in a few number of cases [2–7]. A stunted 6-year-old Kurdish boy was admitted with prolonged epistaxis. According to his medical history, he had had monthly red blood cell transfusions since 5 months of age due to persistent anemia. He experienced several tetanic episodes treated with intravenous calcium, and developed prominent hepatosplenomegaly at the age of 3/2 years. Frequent attacks of epistaxis started at the age of 4 years. He had a splenectomy 1 year later but was still transfusion dependent. His two siblings died of unknown causes at ages of 2 months and 5 years. He also had another 1-year-old sister with failure to thrive with obscure etiology. After admission, laboratory investigations revealed the following levels in his blood: hemoglobin 5.71 g/dL, MCV 88.3 fL, platelets 16.4 × 103/μL, potassium 2.80 mEq/L, calcium 6.6 mg/dL, creatinine 0.8 mg/dL, ferritine 9089 ng/mL, 25-OH vitamin D 9.4 ng/mL, and parathormone 212.5 pg/mL (15–65 pg/mL). Urinalysis revealed glycosuria (250 mg/dL) and proteinuria (650 mg/dL). Density and pH were 1015 and 7.0, respectively. A trephine bone marrow biopsy revealed 90% cellularity, moderate decrease in erythroid precursors, normal megakaryocytic and granulocytic series, increase in reticuline fibers and colorless clusters of crystals mostly stored in histiocytes. Slit Lamp Examination revealed corneal crystals. Leukocyte cystine level was 36.6 nmol 2 cystein/mg of protein confirming the diagnosis. He suddenly died during sleep at night in the first month of our follow-up. Although cystine crystals were widely seen in bone marrow aspirates, cytopenias, and hematological symptoms were rarely reported in cystinosis cases. There are only 6 case reports in literature describing symptomatic bone marrow involvement in nephropathic cystinosis cases (Table 1). All cases were above 20 years of age, except the 4 year-old boy [7]. Presentation of our case was quite distinct; in addition to the classical findings of renal cystinosis, predominant symptoms such as severe anemia and thrombocytopenia without renal function impairment were also observed. Although hypersplenism was thought to be the cause of anemia and thrombocytopenia

A case of SCNN1A splicing mutation presenting as mild systemic pseudohypoaldosteronism type 1

Abstract Systemic pseudohypoaldosteronism type 1 (PHA1) is characterized by excessive salt loss from the renal tubulus, colon, sweat and salivary glands. Here we present a case of systemic PHA1 whose genetic analysis revealed a homozygous splicing mutation in intron 4 of SCNN1A (c.684+2 T>A) and discuss with the patient’s phenotype. Previously described systemic PHA cases show varying degrees of severity dependent on the mutation. Most of the SCNN1A gene mutations present with a severe phenotype. The long-term follow-up and phenotype of the two reported cases with splicing mutation of the SCNN1A gene are unknown. Our case, with a new splicing mutation of SCNN1A, presented with a severe phenotype in the neonatal period. Since then she has been well without any hospitalization and respiratory illness. Her requirement for medication also decreased gradually. After early infancy she presented a mild systemic PHA1 phenotype up to the age of 39 months. In conclusion, the mutation in the patient is located at the splicing site and is definitely a new and pathogenic one, and the phenotype of the patient was milder as observed in a patient with missense mutation.

STEC HÜS Ön Tanısıyla İzlenen Nadir Bir Akut Renal Zedelenme Nedeni: Rabdomiyoliz

160 kut renal zedelenmenin nedenleri coğrafi, kültürel ve ekonomik değişkenlerin etkisi ile ülkelere ve yaş gruplarına göre farklılıklar göstermektedir.1-5 Almanya 2011 salgınından sonra Türkiye’de yaşanan kısmi salgın ve farkındalığın artması nedeni ile diyare ilişkili hemolitik üremik sendromu (D+HÜS) daha sık görülmeye başlanmıştır.6,7 Ancak HÜS tanısı koyarken tanı kriterleri dikkatle değerlendirilmediği takdirde akut renal zedelenme nedeni atlanabilmekte ve hastanın tedavisi gecikebilmektedir.

Successful treatment of macrophage activation syndrome due to systemic onset juvenile idiopathic arthritis with antithymocyte globulin

level was severely toxic (>30 ng/mL), tacrolimus was withdrawn. After the tacrolimus level decreased to 5 ng/ mL, cyclosporine (CsA) was added to the treatment due to unresponsiveness of steroids (Table 1). Cytopenia in all three cell lines and increased liver enzymes brought the possibility of etoposide toxicity; then, etoposide was withdrawn. During the forth week, she developed headache and dizziness. Due to suspicion of central nervous system involvement, ATG was administered 1.5 mg/kg/day. The next day cranial MRI was reported as normal. However, ATG therapy continued because of persisting clinical and laboratory findings of MAS. All the clinical and laboratory findings improved during the fifth week of the disease after ATG treatment, and interleukin-1 receptor antagonist (IL-1Ra) was obtained and added to therapy for the maintenance treatment of SoJIA [2]. At the end of the sixth week, she was discharged with prednisolone, CsA and IL-1Ra (Table 1). MAS occurs because of cytokine over-production from excessive activation of T lymphocytes and macrophages. It is a potentially fatal complication of rheumatic diseases, which is most frequently seen with SoJIA [3]. SoJIA and MAS occurred during maintenance tacrolimus treatment used for liver transplantation in this case. It could be speculated that being on a calcineurin inhibitor does not prevent development of not only SoJIA but also MAS. The management of MAS includes immunosuppressive drugs, primarily high-dose corticosteroids. However, neither clinical nor laboratory parameters could be controlled with steroids, CsA, IVIG and etoposide in this case (Table 1). Actually, the right drug was IL-1Ra; however, it requires official permission in Turkey, and it takes a long time to obtain the drug. ATG has been reported to be effective in induction of remission in familial hemophagocytic To the Editor,