Beltinge Demircioglu Kılıc

Disruption of PTPRO Causes Childhood-Onset Nephrotic Syndrome

Idiopathic nephrotic syndrome (INS) is a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema. Because it typically results in end-stage kidney disease, the steroid-resistant subtype (SRNS) of INS is especially important when it occurs in children. The present study included 29 affected and 22 normal individuals from 17 SRNS families; genome-wide analysis was performed with Affymetrix 250K SNP arrays followed by homozygosity mapping. A large homozygous stretch on chromosomal region 12p12 was identified in one consanguineous family with two affected siblings. Direct sequencing of protein tyrosine phosphatase receptor type O (PTPRO; also known as glomerular epithelial protein-1 [GLEPP1]) showed homozygous c.2627+1G>T donor splice-site mutation. This mutation causes skipping of the evolutionarily conserved exon 16 (p.Glu854_Trp876del) at the RNA level. Immunohistochemistry with GLEPP1 antibody showed a similar staining pattern in the podocytes of the diseased and control kidney tissues. We used a highly polymorphic intragenic DNA marker-D12S1303-to search for homozygosity in 120 Turkish and 13 non-Turkish individuals in the PodoNet registry. This analysis yielded 17 candidate families, and a distinct homozygous c.2745+1G>A donor splice-site mutation in PTPRO was further identified via DNA sequencing in a second Turkish family. This mutation causes skipping of exon 19, and this introduces a premature stop codon at the very beginning of exon 20 (p.Asn888Lysfs*3) and causes degradation of mRNA via nonsense-mediated decay. Immunohistochemical analysis showed complete absence of immunoreactive PTPRO. Ultrastructural alterations, such as diffuse foot process fusion and extensive microvillus transformation of podocytes, were observed via electron microscopy in both families. The present study introduces mutations in PTPRO as another cause of autosomal-recessive nephrotic syndrome.

Bartter syndrome and growth hormone deficiency: three cases.

BackgroundBartter syndrome is a rare autosomal recessive disorder characterized by hypokalemia, salt loss, and metabolic alkalosis. Short stature is one of the clinical manifestations in these children. Although polyuria, polydipsia, hypokalemia, and salt loss may be responsible for growth retardation, the exact pathogenesis of short stature in Bartter syndrome is not known.Case diagnosis and treatmentIn this study, we present three children diagnosed as having Bartter syndrome with short stature and growth hormone (GH) deficiency. After recombinant human growth hormone therapy (rhGH), their growth velocities were improved.ConclusionsThese results indicate that GH deficiency may contribute to short stature in children with Bartter syndrome, and rhGH therapy would be an excellent adjunctive treatment for short children with this syndrome whose condition is resistant to conventional therapies in terms of growth.

The comparison of dextranomer/hyaluronic acid and polyacrylate-polyalcohol copolymers in endoscopic treatment of vesicoureteral reflux

BACKGROUND Dextranomer/hyaluronic acid (Dx/Ha;Dexell®) and polyacrylate-polyalcohol copolymer (PPC;Vantris®) are the popular tissue-augmenting substances using for the endoscopic injections of vesicoureteral reflux (VUR). The aim of the study is to evaluate and compare Dx/Ha and PPC in terms of effectiveness, injection techniques and complications with special emphasis on vesicoureteral junction obstruction (VUJO). METHODS A total of 95 patients who underwent endoscopic VUR treatment between 2009 and 2015 were retrospectively reviewed. The patients were divided into two groups: group 1: Patients underwent endoscopic treatment with PPC (n=50 patients, 70 renal refluxing units) group 2: Patients underwent endoscopic treatment with Dx/Ha (n=45 patients, 74 renal refluxing units). RESULTS The overall resolution rates based on the number of renal refluxing units studied was 88.6% and 70.3% in group 1 and group 2, respectively. Resolution rates were significantly better in group 1 compared to group 2. VUJO requiring ureteral reimplantation or stent insertion developed in 7 patients in group 1. No VUJO was observed in group 2. VUJO in group 1 was markedly higher than that in group 2. CONCLUSIONS Endoscopic treatment of VUR with PPC promises better resolution rates but higher VUJO rates compared to Dx/Ha.

Pediatric post-streptococcal glomerulonephritis: Clinical and laboratory data

Acute post‐streptococcal glomerulonephritis (APSGN) is the most common post‐infectious glomerulonephritis in childhood. The aim of this study was therefore to identify the possible risk factor(s) responsible for decreased glomerular filtration rate (GFR) in APSGN.

Brachial artery pseudoaneurysm: Rare finding in childhood Behcet's disease

Behcet’s disease (BD) is a chronic multisystemic disorder characterized by recurrent oral aphthosis and genital ulcerations, skin lesions and uveitis. It can affect the gastrointestinal tract, musculoskeletal, pulmonary, neurological and cardiovascular systems. All sizes of vessels can be involved, in both of the arterial and venous systems. A 13-year-old girl presented with swelling and pain in the right upper arm for 3 months. She had recurrent oral ulcerations at least 8–10 times for the last 7–8 months. Her parents were first-degree cousins and her paternal aunt had BD. The patient had acneiform lesions on her face. There were no aphthous lesions in the buccal mucosa or genital region. She had an approximately 13 9 9 cm swelling in the right upper arm (Fig. 1a). We noted the lack of right brachial and radial pulses, and loss of deep sensory nerve in the right arm. Pathergy test was negative. Eye examination was normal. Laboratory results indicated high inflammatory markers: white blood cells, 16 900/mm; C-reactive protein, 134 mg/L (normal, 0–5 mg/L); erythrocyte sedimentation rate, 40 mm/h. All rheumatological tests and HLA-B51 were negative. An approximately 10 9 9 cm right brachial artery pseudoaneurysm was detected on Doppler ultrasonography (USG). BD was therefore suspected. We treated the patient with pulse methylprednisolone for 3 days, and subsequently with per oral steroid, azathioprine and colchicine. Median and ulnar motor conduction and ulnar sensory could not be obtained, and minimal median sensorial innervation was detected on electromyography. Magnetic resonance angiography showed an approximately 122 9 84 mm pseudoaneurysm with thrombosis (Fig. 1b). A definite diagnosis of brachial artery pseudoaneurysm was established on conventional angiography (Fig. 1c). Saphenous–brachial bypass was performed. On histopathology, the arterial wall was thickened, with narrowed lumen and neovascularization. There was foamy macrophage and lymphocyte accumulation in the all layers of the artery wall, together with fibrous thickening of the intima, and adventitial fibrosis. The right radial artery had rapid and resistant monophasic flow and the right ulnar artery could not be visualized on Doppler USG. In the fourth postoperative month, the brachial and radial pulses were too slight, and the fingers were slightly cold and mildly cyanotic. The patient had no deep tendon reflexes, especially in the ulnar area, and there was total forearm muscle atrophy together with loss of superficial ulnar sensory nerve. Superficial radial sensory loss was minimal. The patient had no hand dorsiflexion; hand muscle strength was 2/5, extremity muscle strength was 4/5, and she could not move the thumb and index finger, while other fingers had slight movements. In BD, venous lesions are characterized by thrombosis and arterial lesions are characterized by aneurysm, pseudoaneurysm, thrombosis and stenosis. In children, vascular involvement is seen in 7–12% of cases. Combined arterial and venous involvement occurs more often than arterial or venous involvement alone. Ozen et al. reported on seven pediatric patients. Two patients had superficial vein thrombosis, two patients had atrial or ventricular thrombosis, one had arterial involvement with pulmonary aneurysms, and two had thrombosis of the venous sinuses in the central nervous system. In the same article, the disease was diagnosed 3–24 months before the vascular involvement in four patients, and was concomitant with diagnosis in three patients. In the present patient, BD was diagnosed simultaneously with pseudoaneurysm. The present patient did not meet the full International Study Group (ISG) criteria, similarly to most of the pediatric BD patients. The patient did, however, fulfill the International Criteria for BD (ICBD) and new pediatric BD criteria, given that she had recurrent oral aphthosis history, acneiform lesions on the face, and right brachial pseudoaneurysm. With this clinical picture she scored 4 points according to the ICBD system, and 3 points according to the pediatric BD criteria. The patient received immunosuppressive therapy according to the European League Against Rheumatism (EULAR) recommendation for the management of vascular BD. Immunosuppressive treatment should be started in these patients with arterial disease before open surgical or endovascular intervention, and should be continued after the intervention. Long-term immunosuppressive therapy after open surgery or endovascular intervention is important to limit pseudoaneurysm recurrence. In conclusion, arterial vessel involvement is very rare and important in pediatric BD, and brachial artery pseudoaneurysm has not been reported in children. To the best of our knowledge, this is the first report of pediatric BD with brachial pseudoaneurysm in the literature. New diagnostic pediatric BD Correspondence: Beltinge Demircio glu Kılıc, MD, Department of Pediatric Nephrology, School of Medicine, Gaziantep University, Sahinbey, Gaziantep 27310, Turkey. Email: beltingeiklim @hotmail.com Received 30 March 2016; revised 3 August 2016; accepted 15 August 2016. doi: 10.1111/ped.13149

The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis

BACKGROUND AND OBJECTIVES Infantile nephropathic cystinosis is a severe disease that occurs due to mutations in the cystinosis gene, and it is characterized by progressive dysfunction of multiple organs; >100 cystinosis gene mutations have been identified in multiple populations. Our study aimed to identify the clinical characteristics and spectrum of cystinosis gene mutations in Turkish pediatric patients with cystinosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We identified the clinical characteristics and spectrum of cystinosis gene mutations in Turkish patients with cystinosis in a multicenter registry that was established for data collection. The data were extracted from this registry and analyzed. RESULTS In total, 136 patients (75 men and 61 women) were enrolled in the study. The most common clinical findings were growth retardation, polyuria, and loss of appetite. None of the patients had the 57-kb deletion, but seven novel mutations were identified. The most common mutations identified were c.681G>A (p.Glu227Glu; 31%), c.1015G>A (p.Gly339Arg; 22%), and c.18_21 del (p.Thr7Phefs*7; 14%). These mutations were associated with earlier age of disease onset than the other mutations. To understand the effects of these allelic variants on clinical progression, the mutations were categorized into two major groups (missense versus deletion/duplication/splice site). Although patients with missense mutations had a better eGFR at the last follow-up visit, the difference was not significant. Patients in whom treatment began at age <2 years old had later onset of ESRD (P=0.02). Time to ESRD did not differ between the patients with group 1 and group 2 mutations. CONCLUSIONS The most common cystinosis gene mutations identified in Turkey were c.681G>A (p.Glu227Glu), c.1015G>A (p.Gly339Arg), and c.18_21 del (p.Thr7Phefs*7). Patients with less severe cystinosis gene mutations tend to have better kidney outcome.

Autoimmune Polyglandular Syndrome Type 3c with Ectodermal Dysplasia, Immune Deficiency and Hemolytic-Uremic Syndrome

Autoimmune polyglandular syndrome (APS) is a disorder which is associated with multiple endocrine gland insufficiency and also with non-endocrine manifestations. The pathophysiology of APS is poorly understood, but the hallmark evidence of APS is development of autoantibodies against multiple endocrine and non-endocrine organs. These autoantibodies are responsible for the dysfunction of the affected organs and sometimes may also cause non-endocrine organ dysfunction. The hemolytic-uremic syndrome (HUS) is a serious and life-threatening disease which develops due to many etiological factors including autoimmune disorders. Here, we present an unusual case of APS. Ectodermal dysplasia with immune deficiency and HUS occurred concomitantly in the same patient with APS type 3c. Once the autoantibody generation was initiated in the human body, development of multiple disorders due to organ dysfunction and also autoantibody-related diseases may have occurred.