Wider neck circumference is related to severe asthma in children.

BACKGROUND: Obesity is an established risk factor for asthma in children. Measures of central obesity are reported to be more associated with the severity of asthma in adults. The aim of the study was to investigate the association between fat distribution, which is determined by anthropometric measures including neck circumference (NC) and asthma severity in children. METHODS: Children with asthma who were followed in our pediatric allergy unit were consecutively recruited. Asthma severity was graded according to GINA guidelines. Children whose asthma was controlled with Step 1 or 2 treatment options formed Group 1 (mild asthma), whereas children who needed Step 3, 4, or 5 treatment options formed Group 2 (moderate-to-severe asthma). Anthropometric measures including height, weight, NC, waist circumference, and hip circumference were obtained. RESULTS: A total of 127 children (82 male, 64.6%) with a median age of 8.3 (6.4-11.3) years were included. Atopy was present in 77 (60.6%) patients. 91 patients (71.6) were in the mild asthma group. NC of children with severe asthma was significantly wider than children with mild asthma (29.0 cm (27.0-32.0) vs. 28.0 (26.0-30.0), p = 0.019). The prevalence of children with NC higher than 90th percentile was also more frequent in children with severe asthma (15 [41.7%] vs. 21 [23.1%]). Result of multivariable logistic regression analysis revealed that presence of NC >90th percentile was associated with severe asthma in children (odds ratio; [95% confidence interval] (2.52 [1.05-6.01]; p = 0.038). CONCLUSIONS: Neck circumference, which is a simple anthropometric tool, is associated with asthma severity in children.

Development of a medication adherence scale for familial Mediterranean fever (MASIF) in a cohort of Turkish children.

OBJECTIVES: To develop and assess the validity and reliability of an adherence scale concerning medical treatment in paediatric FMF patients. METHODS: The Medication Adherence Scale in FMF Patients (MASIF) is a 18-item questionnaire that evaluates adherence to medication in four domains. Validation of the instrument was accomplished in paediatric FMF patients (aged 2-18 years) under medication at least for 6 months. The first step was to build up the scale through qualitative approach (with interviews using semi-structured questions). Validation analyses included assessment of feasibility, face and content validity; construct validity, internal consistency and test-retest reliability. RESULTS: One hundred and fifty patients with FMF were enrolled in the study. The mean age of the patients was 11.11±4.02 years and 48.7% of them were male. The MASIF was found to be feasible and valid for both face and content. It correlated with the Morisky Medication Adherence Scale as a gold standard thereby demonstrating good construct validity (r=0.515, p<0.001). Assessment of content validity identified four subscales. The internal consistency, Cronbach's alpha was 0.728. There was a positive and significant correlation between test and retest scores (r=0.843; p<0.001). Also, a significant correlation between parents' and children's reports (r=0.781, p<0.001). CONCLUSIONS: Based on these results, the use of this scale to assess and follow up the adherence to treatment in paediatric FMF patients under medical treatment is recommended.

Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort.

BACKGROUND & AIMS: Proprotein convertase 1/3 (PC1/3) deficiency, an autosomal-recessive disorder caused by rare mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, has been associated with obesity, severe malabsorptive diarrhea, and certain endocrine abnormalities. Common variants in PCSK1 also have been associated with obesity in heterozygotes in several population-based studies. PC1/3 is an endoprotease that processes many prohormones expressed in endocrine and neuronal cells. We investigated clinical and molecular features of PC1/3 deficiency. METHODS: We studied the clinical features of 13 children with PC1/3 deficiency and performed sequence analysis of PCSK1. We measured enzymatic activity of recombinant PC1/3 proteins. RESULTS: We identified a pattern of endocrinopathies that develop in an age-dependent manner. Eight of the mutations had severe biochemical consequences in vitro. Neonates had severe malabsorptive diarrhea and failure to thrive, required prolonged parenteral nutrition support, and had high mortality. Additional endocrine abnormalities developed as the disease progressed, including diabetes insipidus, growth hormone deficiency, primary hypogonadism, adrenal insufficiency, and hypothyroidism. We identified growth hormone deficiency, central diabetes insipidus, and male hypogonadism as new features of PCSK1 insufficiency. Interestingly, despite early growth abnormalities, moderate obesity, associated with severe polyphagia, generally appears. CONCLUSIONS: In a study of 13 children with PC1/3 deficiency caused by disruption of PCSK1, failure of enteroendocrine cells to produce functional hormones resulted in generalized malabsorption. These findings indicate that PC1/3 is involved in the processing of one or more enteric hormones that are required for nutrient absorption.

Genetic screening in adolescents with steroid-resistant nephrotic syndrome.

Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.

QT and JT dispersion and cardiac performance in children with neonatal Bartter syndrome: a pilot study.

BACKGROUND: QT dispersion and JT dispersion are simple noninvasive arrhythmogenic markers that can be used to assess the homogeneity of cardiac repolarization. The aim of this study was to assess QT and JT dispersion and their relation with left ventricular systolic and diastolic functions in children with Bartter syndrome (BS). METHODS: Nine neonatal patients with BS (median age 9.7 years) and 20 controls (median age 8 years) were investigated at rest. Both study and control subjects underwent electrocardiography (ECG) in which the interval between two R waves and QT intervals, corrected QT, QT dispersion, corrected QT dispersion, JT, corrected JT, JT dispersion and corrected JT dispersion were measured with 12-lead ECG. Two-dimensional, Doppler echocardiographic examinations were performed. RESULTS: Patients and controls did not differ for gender and for serum levels of potassium, magnesium, and calcium (p > 0.05). Both study and control subjects had normal echocardiographic examination and baseline myocardial performance indexes. The QT dispersion and JT dispersion were significantly prolonged in patients with BS compared to those of the controls {37.5 ms [interquartile range (IQR) 32.5-40] vs. 25.5 ms (IQR 20-30), respectively, p = 0.014 and 37.5 ms (IQR 27.5-40) vs. 22.5 ms (IQR 20-30), respectively, p = 0.003}. CONCLUSIONS: Elevated QT and JT dispersion during asymptomatic and normokalemic periods may be risk factors for the development of cardiac complications and arrhythmias in children with BS. In these patients the need for systematic cardiac screening and management protocol is extremely important for effective prevention.

Evaluation of the current disease severity scores in paediatric FMF: is it necessary to develop a new one?

OBJECTIVES: Modified adult disease severity scoring systems are being used for childhood FMF. We aim to test the clinical consistency of two common severity scoring systems and to evaluate the correlation of scores with the type of FMF mutations in paediatric FMF patients since certain mutations are prone to severe disease. METHODS: Two hundred and fifty-eight children with FMF were cross-sectionally studied. Assessment of the disease severity was performed by using the modified scoring systems of Mor et al. and Pras et al. Genetic analysis was performed using PCR and restriction endonuclease digestion methods for the presence of 15 FMF gene mutations. FMF mutations were grouped into three based on well-known genotypic-phenotypic associations. Correlation between the mutation groups and the severity scoring systems was assessed. The consistency of the severity scoring systems was evaluated. RESULTS: The results of two scoring systems were not statistically consistent with each other (κ = 0.171). This inconsistency persisted even in a more homogeneous subgroup of patients with only homozygote mutations of M694V, M680I and M694I (κ = 0.125). There was no correlation between the mutation groups and either of the scoring systems (P = 0.002, r = 0,196 for scoring systems of Mor et al.; P = 0.009, r = 0.162 for Pras et al.). CONCLUSIONS: The inconsistency of the two scoring systems and lack of correlation between the scoring systems and mutation groups raises concerns about the reliability of these scoring systems in children. There is a need to develop a scoring system in children based on a prospective registry.

The impact of the Eurofever criteria and the new InFevers MEFV classification in real life: Results from a large international FMF cohort.

INTRODUCTION: New Eurofever/PRINTO classification criteria (EPCC) for Familial Mediterranean Fever (FMF) and other recurrent fevers have been recently developed, together with the classification of the pathogenicity of MEFV variants. OBJECTIVES: To evaluate the impact in real life of both the EPCC and INSAID pathogenicity classification of MEFV variants in the large international Eurofever FMF cohort. METHODS: Baseline demographic, genetic and clinical data of FMF patients included in the Eurofever registry were evaluated. The EPCC and the 2018 INSAID classification for MEFV variants were applied in all eligible FMF patients. RESULTS: Since November 2009, clinical information was available for 1012 FMF (532 males/480 females, 827 children/185 adults) from 119 centres. Complete data were available for 887 patients in whom 623 (70.2%) satisfied EPCC (EPCC+), while 264 (29.8%) did not (EPCC-). The majority of the EPCC- patients (172, 65.1%) displayed negative or non-informative genetics (monoallelic or biallelic benign variants, monoallelic variant of unknown significance). At baseline, colchicine was used in most of EPCC+ patients (88%) and in a lower percentage of EPCC- patients (69%, p < 0.0001), who were treated in a higher proportion with steroid or NSAID on demand (p = 0.003 and 0.008, respectively). Four percent of patients received Anti-IL-1 treatment. CONCLUSIONS: The combination of EPCC and the 2018 INSAID classification of MEFV variants is able to identify two distinct groups of patients, which differ in clinical characteristics, therapeutic approach and response to treatment. EPCC+ patients displayed the typical features of FMF, while EPCC- patients had a more variable phenotype with a lower percentage of response to colchicine.

The distribution of juvenile idiopathic arthritis in the eastern Mediterranean: results from the registry of the Turkish Paediatric Rheumatology Association.

OBJECTIVES: To analyse the demographics, main clinical and laboratory features and subtype distribution of juvenile idiopathic arthritis (JIA) in an eastern Mediterranean country, based on a multicentre registry. METHODS: Between March 2008 and February 2009 with this cross-sectional study, consecutive patients seen with JIA in selected centres were registered through a web-based registry. All patients were classified according to the International League of Associations for Rheumatology (ILAR) criteria. RESULTS: There were 634 patients with a mean age of 11.84 ± 4.66 years and the female/male ratio was 1.2. The distributions of JIA patients according to onset of disease were as follows: systemic 92 (14.5%), oligoarticular extended 26 (4.1%), oligoarticular persistent 234 (36.9%), rheumatoid factor (RF) positive polyarthritis 20 (3.2%), RF negative polyarthritis 129 (20.3%), enthesitis-related 120 (18.9%), psoriatic 13(2.1%). The frequency of uveitis was 15.7% among all of the oligoarthritis patients. Anti-nuclear antibody (ANA) was positive mainly among the oligoarticular onset patients. Twenty-one patients also had Familial Mediterranean fever (FMF). Among systemic JIA patients, the frequency of macrophage activation syndrome (MAS) was 15.2% (n=14). At the end of the mean follow-up of 7.6 ± 4.4 years, 305 (48.1%) patients were defined to have inactive disease on medication, and 106 (16.7%) were completely free of any disease symptoms without medication. CONCLUSIONS: Enthesitis related arthritis had a high frequency whereas psoriatic arthritis was very rare compared to other series. We suggest that there are certain differences in the characteristics of JIA in our eastern Mediterranean population. Thus, genetic studies need to be assessed in these populations separately and findings of genome wide association studies need to be confirmed in different populations.

Diuretic-induced renal length changes in the estimation of renal function with MR urography.

OBJECTIVE: The objective of this study was to evaluate whether administration of a diuretic agent in MR urography has an effect on renal length and to determine whether the increase in length can be used for the assessment of renal function. CONCLUSION: Renal length may change after diuretic injection, and these changes correlate with renal function.

Post-transplant glucose status in 61 pediatric renal transplant recipients: preliminary results of five Turkish pediatric nephrology centers.

To assess the incidence, risk factors and outcomes of PTDM, a total of 61 non-diabetic children (24 girls, 37 boys, age: 14.5 +/- 2.1 yr) were examined after their first kidney transplantation (37.3 +/- 21.6 months) with an OGTT. At baseline, 16 (26.2%) patients had IGT, 45 (73.8%) had NGT, and no patient had PTDM. No significant difference was shown between TAC- and CSA-treated patients in terms of IGT. Higher BMI z-scores (p = 0.011), LDL-cholesterol (p < 0.05) and triglyceride levels (p < 0.01), HOMA-IR (p = 0.013) and lower HOMA-%beta (p = 0.011) were significantly associated with IGT. Fifty-four patients were re-evaluated after six months; eight patients with baseline IGT (50%) improved to NGT, three (19%) developed PTDM requiring insulin therapy, five (31%) remained with IGT, and four patients progressed from NGT to either IGT (two) or PTDM (two). These 12 progressive patients had significantly higher total cholesterol (p < 0.05), triglycerides (p < 0.05), HOMA-IR (p < 0.01) and lower HOMA-%beta (p < 0.0) than non-progressive patients at baseline. We can conclude that post-transplantation glucose abnormalities are common in Turkish pediatric kidney recipients, and higher BMI z-scores and triglyceride concentrations are the main risk factors. Considering that the progressive patients are significantly more insulin resistant at baseline, we suggest that the utility of both HOMA-IR and HOMA-%beta in predicting future risk of PTDM and/or IGT should be evaluated in children.

Clinical and radiographic findings in two brothers affected with a novel mutation in matrix metalloproteinase 2 gene.

The two well-described osteolysis syndromes associated with matrix metalloproteinase-2 deficiency and mutations in the metalloproteinase-2 gene are Torg-Winchester syndrome and nodulosis-arthropathy-osteolysis variant. They are characterized by carpal-tarsal destruction, subcutaneous nodules, and generalized osteoporosis and show autosomal recessive inheritance. Herein, we report two siblings affected with a novel mutation in matrix metalloproteinase 2 gene and discuss their clinical and radiographic findings.

Newly discovered mutations in the GALNT3 gene causing autosomal recessive hyperostosis-hyperphosphatemia syndrome.

BACKGROUND AND PURPOSE: Periosteal new bone formation and cortical hyperostosis often suggest an initial diagnosis of bone malignancy or osteomyelitis. In the present study, we investigated the cause of persistent bone hyperostosis in the offspring of two consanguineous parents. METHODS: Clinical assessment, imaging, and direct sequencing were used to elucidate the etiology of the condition seen in the patient. RESULTS: Radiological examination revealed periosteal reaction, diaphysitis, and cortical hyperostosis, suggesting osteomyelitis or a bone neoplasm. The clinical and radiological features were also reminiscent of hyperostosis with hyperphosphatemia (HHS), a rare autosomal recessive disease manifesting with recurrent, transient, and painful swelling of the long bones. The identification of two novel heterozygous pathogenic mutations in the GALNT3 gene confirmed a diagnosis of HHS. INTERPRETATION: Molecular analysis represents an invaluable tool in the differential diagnosis of persistent cortical hyperostosis.

A very frequent mutation and remarkable association of R761H with M694V mutations in Turkish familial Mediterranean fever patients.

Familial Mediterranean fever (FMF) is an autosomal-recessive disease. It is characterized by recurring fever, abdominal pain, and serositis. The Mediterranean fever (MEFV) gene is localized on 16p13.3 and more than 35 mutations have been described to date. There are some differences in the gene mutations of FMF in the various ethnic groups. The aim of this study is to determine the frequency of the mutations which has been reported comparatively rare, to define the most effective mutation set, and to select the most suitable DNA analysis system for Turkish FMF patients. Mutations in 330 Turkish FMF patients with typical phenotypes from various regions of Turkey were evaluated for the research purposes. These patients were analyzed for six MEFV gene mutations by the NanoChip Molecular Genetics Workstation. The most frequent mutation was M694V, identified in 50.00% of the alleles examined; M680I followed with 14.10% and V726A--9.70%. Consequently, we determined that R761H (n = 23; 3.48%) was the most frequent rare mutations in Turkish FMF patients. Frequency of the rare mutations were R761H (3.48%), E148Q (1.36%), and M694I (1.21%). All of these mutations were in the compound heterozygote state. Our study showed that R761H mutations were higher than it has been reported in literature until now and were mainly associated with M694V. We suggest that mutation R761H should be included in the mutation scanning analysis researches or considered if the patient has M694V/? mutation especially in Turkish FMF patients. Larger serial studies need to be done to investigate the rate and coexistence of these mutations.

Electronic microarray screening of podocin mutations: a single-center study.

BACKGROUND: Because of resistance to immunosuppressants in nephrotic syndrome and reduction of proteinuria relapses following renal transplantation, it seems that new horizons have arisen from mutational screening of the podocin gene. The aim of this study was to assess electronic microarray screening of the podocin mutation. METHODS: Twelve previously identified podocin mutations were screened by the electronic microarray method in known DNA samples and in patients (aged 5 months-18 years, n = 38) with steroid-resistant primary nephrotic syndrome, isolated proteinuria, end-stage renal disease secondary to idiopathic nephrotic syndrome, and proteinuria relapses following renal transplantation. RESULTS: DNA samples previously supplied to define the mutation profile for analysis and which were used as controls were completely and correctly detected by this method. None of the 12 mutations was detected in our patients. The duration of analysis for one mutation, including hybridization, was only 30 min for 38 cases. CONCLUSION: Electronic microarray screening for NPHS2 mutations is not only rapid but also accurate. Previous identification of the mutation profile most often encountered in the investigated population is needed, however.

Childhood vasculitides in Turkey: a nationwide survey.

AIM: The aims of this study were to evaluate the characteristics of childhood vasculitides and to establish the first registry in Turkey, an eastern Mediterranean country with a white population. PATIENTS AND METHODS: A questionnaire was distributed to the main referral centers asking for the registration of the Henoch-Schönlein purpura (HSP) patients in the last calendar year only and 5 years for other vasculitides. Demographic, clinical, and laboratory data were assessed. RESULTS: Vasculitic diseases were registered from 15 pediatric centers. These centers had a fair representation throughout the country. In the last calendar year, incidences were as follows: HSP 81.6%, Kawasaki disease (KD) 9.0%, childhood polyarteritis nodosa (C-PAN) 5.6%, Takayasu arteritis (TA) 1.5%, Wegener's granulomatosis 0.4%, and Behçet disease 1.9%. There was no clear gender dominance. The mean age was 11.05+/-4.89 years. Acute phase reactants were elevated in almost all, highest figures being in C-PAN. Renal involvement was present in 28.6% of HSP and 53% of the C-PAN patients. Abdominal aorta was involved in all TA patients. Among the C-PAN patients, 25% had microscopic PAN with necrotizing glomerulonephritis; antineutrophil cytoplasmic antibody was positive in those who were studied. Among the patients, 12.5% and 15% had classic PAN and cutaneous PAN, respectively. The remaining majority were classified as systemic C-PAN diagnosed with biopsies and/or angiograms demonstrating small to midsize artery involvement. The overall prognosis was better than reported in adult series. CONCLUSION: This is the largest multicenter study defining the demographic data for childhood vasculitides. The distribution of childhood vasculitides was different in our population where KD is much less frequent, whereas HSP constitutes an overwhelming majority. C-PAN was more frequent as well.

Assessment of autonomic functions in children with familial Mediterranean fever by using heart rate variability measurements.

AIM: The aim of this study is to analyze possible autonomic nerve system alterations and assess the efficacy of heart rate variability (HRV) analysis in anticipation of cardiovascular risks in pediatric patients with familial Mediterranean fever (FMF). METHOD: In this study, cardiac autonomic functions were investigated in children with FMF by analyzing HRV and its other probable cardiac effects by echocardiography. We studied 70 pediatric patients with FMF and 50 healthy controls. RESULTS: The time-domain parameters of HRV were compared between the FMF and control groups. SDNN (standard deviation of all NN intervals) was significantly decreased in patients with FMF as compared to control subjects. The other time-domain parameters of HRV and the frequency-domain parameters of HRV were similar in both groups. Frequency-dependent HRV parameters were similar in both groups, as were conventional echocardiographic parameters. CONCLUSION: HRV is a convenient and reliable technique for evaluation of autonomic functions. There are only a few studies on the assessment of autonomic functions by means of HRV in adult FMF patients but not in pediatric patients. Further studies are required to assess whether there is autonomic dysfunction in children with FMF.

Effect of Voided Volume on Voiding Patterns and Reliability of Uroflowmetry-Electromyography Results in Children with Lower Urinary Tract Dysfunction.

OBJECTIVE: To examine whether voided volume (VV) could change the uroflow patterns and result in children with lower urinary tract dysfunction (LUTD). METHODS: Between January 2009 and May 2010, the children with LUTD were enrolled in this study. Uroflowmetry (UF) combined with electromyography (EMG) was performed two times and was reviewed independently by two urologists. UF-EMG curves were classified as bell, staccato, intermittent, plateau, and tower. Patients' expected bladder capacity (EBC) and VV were recorded. Patients were divided into four groups according to their VV and EBC. Group 1, VV <50% of EBC; group 2, VV between 50 and 100% of EBC; group 3, VV between 100 and 125% of EBC; group 4, VV >125% of EBC. RESULTS: A total of 143 patients underwent UF-EMG at least two times and 382 results were obtained. Groups 1, 2, 3 and 4 consisted of 27, 60, 27 and 29 children, respectively. The percentages of normal, intermittent, plateau voiding patterns were 58.5, 12.8, 7.1% in group 1; 79.8, 5.4, 1.8% in group 2; 59.2, 8.5, 2.8% in group 3; and 37.2, 5.1, 2.6% in group 4, respectively. The percentages of staccato and tower pattern were 1.4, 20% in group 1; 9.1, 3.6% in group 2; 30, 0% in group 3; and 55.1, 0% in group 4, respectively. The rate of tower shape curve decreased as voided volume increased, but the rate of staccato curve increased as voided volume increased. CONCLUSIONS: In case of exceeding the EBC, the test should be repeated with normal VV when UF results are being evaluated.

Novel OCRL1 mutations in patients with the phenotype of Dent disease.

BACKGROUND: Dent disease is an X-linked tubulopathy frequently caused by mutations affecting the voltage-gated chloride channel and chloride/proton antiporter ClC-5. A recent study showed that defects in OCRL1, encoding a phosphatidylinositol 4,5-bisphosphate 5-phosphatase (Ocrl) and usually found mutated in patients with Lowe syndrome, also can provoke a Dent-like phenotype (Dent 2 disease). METHODS: We investigated 20 CLCN5-negative males from 17 families with a phenotype resembling Dent disease for defects in OCRL1. RESULTS: In our complete series of 35 families with a phenotype of Dent disease, a mutation in the OCRL1 gene was detected in 6 kindreds. All were novel frameshift (Q70RfsX88 and T121NfsX122, detected twice) or missense mutations (I257T and R476W). None of our patients had cognitive or behavioral impairment or cataracts, 2 classic hallmarks of Lowe syndrome. All patients had mild increases in lactate dehydrogenase and/or creatine kinase levels, which rarely is observed in CLCN5-positive patients, but frequently found in patients with Lowe syndrome. To explain the phenotypic heterogeneity caused by OCRL1 mutations, we performed extensive data-bank mining and extended reverse-transcriptase polymerase chain reaction analysis, which provided no evidence for yet unknown (tissue-specific) alternative OCRL1 transcripts. CONCLUSION: Mutations in the OCRL1 gene are found in approximately 23% of kindreds with a Dent phenotype. Defective protein sorting/targeting of Ocrl might be the reason for mildly elevated creatine kinase and lactate dehydrogenase serum concentrations in these patients and a clue to suspect Dent disease unrelated to CLCN5 mutations. It remains to be elucidated why the various OCRL1 mutations found in patients with Dent 2 disease do not cause cataracts.

Minimal change nephropathy in a 7-year-old boy with Rosai-Dorfman disease.

Rosai-Dorfman (R-D) disease is a benign lympho-histiocytosis of the lymphoid system. Immune derangement due to cytokine over-expression (tumor necrosis factor (TNF), interleukin (IL)-1b and IL-6) has been considered the cause of R-D disease. We present a 7-year-old boy with R-D disease who developed minimal change nephropathy (MCN) during the progression of R-D disease. The patient was resistant to oral prednisolone; and the remission of both R-D disease and MCN was achieved with oral cyclophosphamide (2 mg/kg, 12 weeks). MCN, the most common cause of nephrotic syndrome in childhood, is generally accepted to emerge by way of cytokine derangement. Correlation between R-D disease activity and the development and remission of nephrotic syndrome in our case suggested that nephrotic syndrome had been induced through some R-D disease-related immune mechanisms.