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OCRL mutations, which are a hallmark of Lowe syndrome, have recently been found in patients with isolated renal phenotype (Dent-2 disease). In this report, we describe clinical and laboratory features in five Macedonian children with mutations in the OCRL gene. Children with a clinical diagnosis of Lowe syndrome or Dent disease underwent complete neurological and ophthalmological examination, imaging of the kidney and urinary tract, assessment of renal tubular function, and mutation analysis of the OCRL gene. Two children (18 months and 11 years, respectively) were diagnosed with Lowe syndrome on the basis of congenital cataracts, severe psychomotor retardation, and renal dysfunction. Both children had low molecular weight proteinuria (LMWP) and hypercalciuria, but not Fanconi syndrome. The older one had bilateral nephrolithiasis due to associated hypocitraturia and mild hyperoxaluria. Three children with asymptomatic proteinuria were diagnosed with Dent-2 disease; none had cataracts or neurological deficit. One child showed mild mental retardation. All had LMWP, hypercalciuria, and elevated enzymes (creatine phosphokinase, lactic dehydrogenase). All three children had an abnormal Tc-99m DMSA scan revealing poor visualization of the kidneys with a high radionuclide content in the bladder; none had nephrolithiasis or nephrocalcinosis. In conclusion, children with OCRL mutations may present with very mild phenotype (asymptomatic proteinuria with/ without mild mental retardation) or severe classic oculocerebrorenal syndrome of Lowe. Elevated enzymes and abnormal results on the Tc-99m DMSA scan may be useful indicators for Dent-2 disease. Keywords Oculocerebrorenal syndrome * Dent-2 disease * OCRL * Low molecular weight proteinuria * Hypercalciuria, Introduction Oculocerebrorenal syndrome of Lowe (OMIM 309000) was reported for the first time by Lowe et al. in 1952 [1]. This is an X-linked recessive multisystem disorder characterized by the [...]

Copyright of Contributions / Prilozi (1857-9345) is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Contributions / Prilozi (1857-9345) is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Vitamin D has several important functions including absorption of calcium and phosphorous, and facilitating normal immune system function. Sufficient amount of the vitamin is required for normal growth and development of bones and teeth, as well as improved resistance against certain diseases. There is growing evidence that there are huge benefits of vitamin D in promoting the human health, not only in infants for prevention of rickets but also effects on the immune system, blood pressure, reducing the risk of some cancers, prevention of diabetes mellitus type 1 trough stimulation of the pancreatic beta cells to secrete insulin. In contrast to these benefits certain patients genetically predisposed are at risk to develop a serious even fatal disease such as idiopathic infantile hypercalcemia. Withdrawal of vitamin D and reduction of calcium intake are lifesaving interventions for these babies. Recently it was found that recessive mutations in CYP24A1 gene are responsible for this disease. This gene encodes the enzyme 24 vitamin D hydroxylase which is important in the degradation metabolic pathway of the vitamin D. Although it was generally believed that idiopathic infantile hypercalcemia is the disease limited to infancy a number of studies yields that adults may have serious morbidity including nephrolithiasis, nephrocalcinosis, intermittent episodes of hypercalcemia leading to chronic kidney disease and in few cases to end stage renal disease. Therefore one should be very cautious in liberal prescribing vitamin D supplements and excessive exposure to sunlight, particularly in individuals with genetic predisposition. [ABSTRACT FROM AUTHOR]

Nephrotic syndrome is defined as the association of massive proteinuria, hypoalbuminaemia, edema, and hyperlipidemia. It is separated to steroid-sensitive or steroid-resistant (SRNS) forms in respect to the response to intensive steroid therapy. SRNS usually progresses to end-stage renal failure. According to the North American Pediatric Renal Trials and Collaborative Studies SRNS constitutes the second most frequent cause of ESRD in the first two decades of life. Unfortunately, there is no curative treatment for majority of patients. Majority of the SRNS patients have the histologic picture of focal segmental glomerulosclerosis. Interestingly, the risk of recurrence in the kidney graft in patients with hereditary SRNS is lower than in those who do not have genetic background. The etiology and pathogenesis of SRSN has remained enigma for decades. The discovery of 39 dominant or recessive SRNS genes enabled better understanding of the function of the glomerular podocytes and slit membrane. Hildebrandt′s group has shown that 85% of the SRNS cases with onset by 3 months of age and 66% with onset by 1 year of age can be explained by recessive mutations in one of four genes only (NPHS1, NPHS2, LAMB2, or WT1). The same group used modern diagnostic techniques such as the next generation sequencing and tested a large international cohort of SRNS patients (n = 1783 families). The diagnostic panel included 21 genes with a recessive mode of inheritance and 6 genes with a dominant mode of inheritance. Single-gene cause was detected in 29.5% (526 of 1783) of the families with SRNS that manifested before 25 years of age. The identification of causative single-gene mutations may have important therapeutic consequences in some cases. This is very important for patients who carry mutations in a gene of coenzyme Q10 biosynthesis (COQ2, COQ6, ADCK4, or PDSS2). In these patients the treatment with coenzyme Q10 may be indicated. Also, patients with recessive mutations in PLCE1 may respond fully to the treatment with steroids or cyclosporine A. The patients with CUBN may benefit the treatment with vitamin B12. The detection of causative mutations may also be very important for familial genetic counseling and for prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Diabetes mellitus type 1 (T1DM) is a chronic disease with long term consequences dictating daily struggle to maintain a good metabolic control. Children and adolescents with T1DM seem to have inferior psychological adjustment to their normal counterparts, which might be associated with glycemic control and disease duration. The aim of this study is to evaluate the psychological characteristics of children and adolescents with T1DM treated last year in the University Children Hospital in Skopje, Macedonia and to propose some response measures. For psychological evaluation we used CBCL (Child Behavior Check List), GAS (General Anxiety Scale), EPQ (Eysenck Personality Questionnaire) and MMPI-201 (Minnesota Multiphasic Personality Inventory). The results confirmed the following psychological characteristics: mild depression and anxiety, emotional instability, need for social acceptance, as well as the possible psychopathic traits. Suffering for a complex metabolic and chronic illness, these patients need psychological evaluation and intervention in the management. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to assess clinical course and outcome of children with congenital anomalies of the kidney and urinary tract (CAKUT) who had an attack of acute poststreptococcal glomerulonephritis (PSGN).Method: Renal status including blood pressure, proteinuria and glomerular filtration rate was retrospectively analyzed in five children with CAKUT and PSGN at the presentation and during the follow up.Results: In the period 2004–2013, 678 patients were diagnosed and recruited in our CAKUT cohort. During this period, 188 patients were hospitalized with the diagnosis of PSGN. A total of five patients had CAKUT and an episode of PSGN (2.6%). Analysis of the follow-up data revealed that three children fully recovered (bilateral vesicoureteral refluxn = 1, ectopic/hypodysplastic kidneyn = 1, ureteropelvic junction obstructionn = 1). One child with bilateral hypodysplasia had progressive worsening of the renal function and has been prepared for renal replacement therapy. Another child with single kidney has stable renal function but has significant rising proteinuria, which was not evident on the routine analysis 2 months before the attack of PSGN.Conclusion: Poststreptococcal glomerulonephritis in children is generally benign disease with low mortality in acute stage and excellent medium and long-term prognosis. We analyzed our series of PSGN patients and found that 2.6% had anomaly of the urinary tract. The unfavorable outcome was noted in children with single kidney and bilateral renal impairment. [ABSTRACT FROM PUBLISHER]

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare and heterogeneous disorder. The first line treatment of aHUS is plasma therapy, but in the past few years, the recommendations have changed greatly with the advent of eculizumab, a humanized monoclonal anti C5-antibody. Although recent recommendations suggest using it as a primary treatment for aHUS, important questions have arisen about the necessity of immediate use of eculizumab in all cases. We aimed to draw attention to a specific subgroup of aHUS patients with rapid disease progression and high mortality, in whom plasma therapy may not be feasible. Methods: We present three pediatric patients of acute complement-mediated HUS with a fatal outcome. Classical and alternative complement pathway activity, levels of complement factors C3, C4, H, B and I, as well as of anti-factor H autoantibody and of ADAMTS13 activity were determined. The coding regions of CFH, CFI, CD46, THBD, CFB and C3 genes were sequenced and the copy number of CFI, CD46, CFH and related genes were analyzed. Results: We found severe activation and consumption of complement components in these patients, furthermore, in one patient we identified a previously not reported mutation in CFH (Ser722Stop), supporting the diagnosis of complement-mediated HUS. These patients were not responsive to the FFP therapy, and all cases had fatal outcome. Conclusion: Taking the heterogeneity and the variable prognosis of atypical HUS into account, we suggest that the immediate use of eculizumab should be considered as first-line therapy in certain small children with complement dysregulation. [ABSTRACT FROM AUTHOR]

Obesity and overweight are a pandemic phenomenon in the modern world. Childhood and adolescent obesity often ends up in obesity in adults. The costs of obesity and its consequences are staggering for any society, crippling for countries in development. The etiology is complex, but most often idiopathic. Hormonal, syndromic and medication-induced obesity are well investigated. Genetic causes are increasingly described. Novel technologies such as whole exome sequencing identify ever more candidate genes influencing or causing obesity. All insights into the complex problem of obesity in a team approach to treatment: diet, psychology, medications and surgery. We briefly review epidemiology, etiology, consequences and treatment approaches in childhood and adolescent obesity, with special emphasis on emerging knowledge of its genetics. [ABSTRACT FROM AUTHOR]

Background: Peripheral biofeedback is considered to be an efficient method for assessment and stress mitigation in children. The aim of the present study was to assess the levels of stress and stress mitigation in healthy school children (HSC), in children with cystic fibrosis (CF), general anxiety (GA) and attention-deficit–hyperactivity disorder (ADHD). Methods: Each investigated group (HSC, CF, GA, ADHD) consisted of 30 school-aged children from both sexes. Psychological characteristics were evaluated on Eysenck Personality Questionnaire (EPQ). The lie scale was used to determine participant honesty. Four biofeedback games using a pulls detector were applied for assessment of the stress levels as well as to evaluate ability to relax. Results: EPQ found more psychopathological traits ( P < 0.001) and less extroversion ( P < 0.001) in children with GA and ADHD. In addition, high neurotic tendencies were found in children with CF ( P < 0.01) and GA ( P < 0.01). Unexpectedly, the lie scale was lower in ADHD children ( P < 0.01) than in all other groups (HSC, CF, GA). The Magic blocks score was significantly different in relaxation levels between control and CF children ( P < 0.05). Speed in the game Canal was significantly different in relaxation levels between healthy controls and all other groups, but no changes in pulls, as a relaxation measure, were found during the game. The CF group had much more commissions stemming from impulsivity ( t= 5.71, P < 0.01), while the GA and ADHD children had more inattention omissions ( P < 0.05). Strong negative correlation between age and pulls ( r= 0.49, P= 0.003) and strong negative correlation between age and omissions ( r=−0.86, P= 0.029) were found among all groups analyzed. Conclusions: The ability to learn stress mediation is correlated with age. All three groups of children had significantly lower relaxation levels when compared to healthy controls. Relaxation was more difficult for children with GA or ADHD, and easier for children with CF. [ABSTRACT FROM AUTHOR]