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Anderson-Fabry Disease (AFD) is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a deficient or absent activity of the lysosomal enzyme, α-galactosidase A, resulting in the progressive multisystem lysosomal accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3). Among the wide spectrum of clinical signs and symptoms and the life-threatening complications of Fabry disease, renal failure causes significant morbidity and mortality. Various evidence shows that the accumulation of Gb3 in different renal cells is present since the first years of life, many years and usually decades before manifest symptoms and signs of renal involvement. Early renal damage can be demonstrated by clinical signs as microalbuminuria and proteinuria, developing as early as in the second decade of life. A decline in GFR is uncommon at paediatric ages but may be seen as early as adolescence. Renal biopsy is rarely used in paediatric patients with Fabry disease although evidence shows that it may be considered a valid tool for the diagnosis of early and potentially reversible nephropathy, as well as for the evaluation of the effectiveness of enzyme replacement therapy (ERT). Although there is consensus in considering the early initiation of ERT as the only tool able to prevent the progression of nephropathy, the issue on the correct timing for the onset of ERT in pediatric age remains open in the management of this chronic and progressive disease.

Nocturnal enuresis (NE) was defined by the World Health Organization (ICD-10) and the American Psychiatric Association (DSM-5) as bed-wetting in children aged5 years. In cases of mental retardation, the developmental age may be equivalent to 5 years. In this review, we focus on the current knowledge about the etiology of enuresis and the most recent therapeutical options. Both non-pharmacological and pharmacological therapies are included, although the relative effectiveness of each remains uncertain. To date, motivational, alarm and drug therapies are the mainstay of treatment. Alarm therapy remains the first-line treatment modality for NE, while desmopressin is the most commonly used medical treatment.

Nephrotic Syndrome (NS) is a rare diseases (around 2-7 cases per 100.000 children per year) characterized by proteinuria ≥50 mg/kg/day (or ≥40 mg/m2/h) or a proteinuria/creatininuria ratio2 (mg/mg); hypoalbuminaemia less than 25 g/l and edema. The protein leakage, with the consequent hypoalbunaemia and edema, due to podocyte alterations may be caused by genetic diseases, immunological mechanisms, infections, toxins or malignancy. However, most commonly the exact etiology is unknow. The idiopathic NS may be classified based on response to corticosteroid therapy or the hytological appearance. The first classification identifies steroid-resistant NS (no response after 4 weeks of steroid therapy); frequently relapsing NS (≥ 2 relapses in first 6 months or ≥4 relapses in 1-year); steroid dependent NS (relapses during steroid decalage or within 2 weeks from steroid therapy interruption). The hystological classification is based on light and electron microscopy after renal biopsy, which is indicated in case of onset disease before 1 year or after 12 years of age. Macroscopic hematuria: persistent hypertension and/or microscopic hematuria and/or low plasma C3 renal failure not related to hypovolemia; steroid resistence: secondary or relatedsyndromes NS. Minimal change disease (MCD) is the most common form of idiopahtic NS in children, with good response to steroid treatment, and it is characterized by normal glomerular appearance on light microscopy and evidence of podocyte foot alterations on electron microscopy, due to immunological related damage. Focal segmental glomerulosclerosis (FSGS) is described inidiopahtic NS, particularly in steroiddependent or steroid-resistant forms, and is characterized by evidence of focal glomerular damage with secondary sclerosis and adhesion with Bowman's capsule; the electron appearance is the same of MCD one. Recent authors hypotizethat the FSGS is an evolution of MCD. These 2 idiopathic NS forms may be expression of the same immunological disease, with 2 different severity grades; so they may be considered different moments of the same disease spectrum. Less common idiopathic NS forms are membrano proliferative glomerulonephritis; membranous nephropathy; IgM-nephropathy; C1q nephropathy and thin basement membrane disease (1, 2, 3).

Low birth weight (LBW) is associated with reduced nephron endowment. Clinical–pathologic features of post adaptive focal segmental glomerulosclerosis (FSGS) have been observed in subjects with prematurity and very LBW. We aimed to investigate the correlation between LBW and outcome in a cohort of 89 children with idiopathic nephrotic syndrome (NS) (2–12 years-old at onset, followed for > 3 years), of whom 21 with LBW (birth weight

Peritonitis, the most important limitation of peritoneal dialysis (PD), could be detected by biomarkers in dialysate effluent, representing a noninvasive method to indirectly assess the peritoneum status. The aim of our study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating its role as precocious marker of peritoneum damage during peritonitis. Transforming growth factor (TGF)-β was correlated with peritoneal transport characteristics.Six patients, treated by ambulatory PD, were enrolled. Samples were collected at the onset of peritonitis (T1) and every day until its resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was also evaluated. Peritoneal Equilibration Test evaluated the filter activity of peritoneum.In patients with acute peritonitis, the highest serum and peritoneal HMGB1 values (64 ± 3.6 and 70 ± 5.3 ng/mL, respectively) were assessed, with a progressive decrease of their levels at the resolution time (T-end: sHMGB1:36 ± 2.5; pHMGB1:30.5 ± 7.0 ng/mL). While no differences of sWBC and pWBC were observed between baseline and T-end values, pHMGB1 levels remained higher at T-end than those observed at T0 (pHMGB1:30.5 ± 7.0 versus 6.9 ± 3.6; p 0.0001). TGF-β levels were higher in patients with low peritoneal permeability than in medium or high transporter patients (81 ± 15.5 versus 24.3 ± 7.5 pg/mL; p = 0.01). An inverse correlation was found between TGF-β levels and dialysate/plasmatic creatinine values (r = -0.83; p = 0.03).HMGB1 represents a useful biomarker for peritoneum evaluation in PD patients. A prognostic role of this alarmin, as a marker of response to therapy, could be hypothesized. TGF-β could predict the peritoneal transport status and dialysis technique adequacy.

Background: Data from routine clinical practice are needed to further define the efficacy and safety of biologic medications in children with juvenile idiopathic arthritis (JIA). The aim of this analysis was to investigate the disease status, reasons for discontinuation and adverse events in Italian JIA patients treated with etanercept (ETN). Methods: In 2013, all centers of the Italian Pediatric Rheumatology Study Group were asked to make a census of patients given ETN after January 2000. Patients were classified in three groups: group 1 = patients still taking ETN; group 2 = patients discontinued from ETN for any reasons; group 3 = patients lost to follow-up while receiving ETN. All three groups received a retrospective assessment; patients in group 1 also underwent a cross-sectional assessment. Results: 1038 patients were enrolled by 23 centers: 422 (40.7%) were in group 1, 462 (44.5%) in group 2, and 154 (14.8%) in group 3. Median duration of ETN therapy was 2.5 years. At cross-sectional assessment, 41.8% to 48.6% of patients in group 1 met formal criteria for inactive disease, whereas 52.4% of patients in group 2 and 55.8% of patients in group 3 were judged in clinical remission by their caring physician at last visit. A relatively greater proportion of patients with systemic arthritis were discontinued or lost to follow-up. Parent evaluations at cross-sectional visit in group 1 showed that 52.4% of patients had normal physical function, very few had impairment in quality of life, 51.2% had no pain, 76% had no morning stiffness, and 82.7% of parents were satisfied with their child's illness outcome. Clinically significant adverse events were reported for 27.8% of patients and ETN was discontinued for side effects in 9.5%. The most common adverse events were new onset or recurrent uveitis (10.2%), infections (6.6%), injection site reactions (4.4%), and neuropsychiatric (3.1%), gastrointestinal (2.4%), and hematological disorders (2.1%). Ten patients developed an inflammatory bowel disease and 2 had a malignancy. One patient died of a fulminant streptococcal sepsis. Conclusions: Around half of the patients achieved complete disease quiescence under treatment with ETN. The medication was overall well tolerated, as only one quarter of patients experienced clinically significant adverse events and less than 10% had treatment discontinued for toxicity.

Nephrotic syndrome is a condition of massive proteinuria that leads to hypoalbuminaemia and oedema. In the pediatric age, the most common form of nephrotic syndrome is childhood idiopathic nephrotic syndrome (CINS). Although the etiological mechanisms underlying CINS are still unclear, the disease is considered to be immune-mediated. Several studies have previously reported a possible association between CINS and atopy, with the latter defined as abnormal immunoglobulin-E response on the background of a T-helper 2 (Th2)-driven immune system. In fact, both experimental and clinical studies have suggested that idiopathic nephrotic syndrome can be associated and/or triggered by a wide array of atopic diseases, though this remains a highly controversial topic. Exposure to inhalant-allergens (and/or introduction of food-allergens) has been previously correlated with the onset and/or the relapse of CINS in some children and a significant worse response to steroid therapy has been also described in reports of CINS associated to concomitant atopic diseases. In this review, we analyzed previous studies with the aim to clarify, basing on the existent literature, the association between atopy and idiopathic nephrotic syndrome. Additionally, we also speculated on the underlying immunological pathways that could potentially make some children prone to both CINS and atopic diseases.

Vitamin D (VitD) intoxication, a well-known cause of hypercalcaemia in children, has renal, cardiac and neurological consequences. Iatrogenic or accidental administrations are the most common causes. We present two cases of hypervitaminosis D due to over-the-counter VitD supplement self-medication. A 12-year-old boy was hospitalised for abdominal pain, constipation and vomiting. Routine biochemistry indicated severe hypercalcaemia and renal failure. Plasma 25-OH VitD level was very high and parathyroid hormone was suppressed. Renal ultrasound showed nephrolithiasis. Hydration, diuretics and prednisone induced a progressive reduction of calcium levels. His brother, who was receiving the same treatment, was hospitalised although asymptomatic. Normal serum calcium and renal function were revealed, while 25-OH VitD was high and parathyroid hormone was suppressed. Renal ultrasound was within the normal range. Examination of the VitD content of the over-the-counter supplement revealed a higher amount than declared. VitD administration implies several risks and must be prescribed only when needed and under strict medical control.

Although epidemiological and clinical features strongly suggest an infectious cause, the etiology of Kawasaki disease (KD) still remains unknown. The hypothesis that bacterial toxins acting as superantigens could trigger the cascade of events leading to KD has been widely debated. We report four children with typical KD in whom a serological evidence of Mycoplasma pneumoniae infection was detected.

In the older, the presenting symptoms were fever and migrant arthralgias. At onset, she was 6 year old. Laboratory work-up showed increased ESR, CRP, PTL count, and anaemia. Over time she developed ischemic colitis and a transient cerebral ischemic attack. Cerebral Angio MRI revealed multiple periventricular hyperintensities prompting the diagnosis of PAN. Steroids, cyclophosphamide, methotrexate, and azathioprine were unsuccessful, and the disease was complicated by neuropathy and ischemic lesions of several digits. Thalidomide was started in December 2003; since then, the disease is stable and laboratory work up normal. First clinical features of the younger sister occurred at three years of age. She had an acute stroke. Following hypertension, renal disease and neuropathy, PAN was diagnosed. Steroids, azathioprine and cyclophosphamide were given with scarce benefit. After another ischemic cerebrovascular event, thalidomide was effective in controlling the disease activity.

Their medical history of recurrent fever attacks started at the age of 14 and 6 months respectively. Fever was accompanied by cervical adenopathy, severe exudative pharyngitis, oral aphtosis, abdominal pain and diarrhoea, sometimes with bloody stools. At the age of 10 and 9 years, screening for autoinflammatory disorders was performed revealing a single mutated FMF gene (E148Q). Since they fulfilled Tel Hashomer criteria, colchicine was started.

Familial Mediterranean Fever (FMF) is an autosomal recessive disease (MEFV gene) characterized by recurrent fever and inflammatory serositis. Although majority of patients have random pattern of attacks, some reports described precipitating factors. A literature review indicated that FMF attacks occurring only during menstruation are rarely seen. We report the cases of three patients with severe dysmenorrhoic pain as unusual clinical presentation of FMF. They were 3 females with a mean age at onset of 12 years. They never had typical attacks of fever and abdominal or chest pain, but they suffered from regular and severe dysmenorrhoic pain. Leukocytosis and C-reactive protein (CRP) elevation were noted during these attacks in all patients. Unlike dysmenorrhoea, none of these patients' attacks responded to non-steroidal anti-inflammatory drugs. The diagnosis of FMF was based on typical clinical and laboratory features. On investigation of MEFV, M694V was the most frequent mutation All patients responded well to colchicine, and amyloidosis was not documented in any patients. In conclusion, we suggest that gynecologists must be aware of FMF in the differential diagnosis of dysmenorrhoea or endometriosis especially in the people of Mediterranean origin.[1]

Clinical case A sixteen year old boy presented, three years before, gastrointestinal (abdominal pain, vomiting, diarrhea) and neurologic symptoms (headache, diplopia, ataxia, VI nerve paralysis), with fever, oral and genital aphtosis. Laboratory tests showed increased ESR, CRP). He carried B51HLA. Physical examination showed svere obesity, pseudomicropenis, rare pubic hair, pubertal stage G2P2. Thus BD was diagnosed. Treatment with corticosteroids and antiplatelet agents was started.

Renal ectopia is a malformative uropathy classified as simple and crossed. The authors report two patients with renal ectopia (one case of ERC without fusion and one case of ERC with fusion). The authors review the literature about crossed renal ectopia and discuss the importance of early diagnosis and the advantage of thorough investigation in order to exclude associated anomalies.

Background Henoch-Schoenlein purpura (HSP) is the most common vasculitis in children, characterized by multisystem involvement. Renal complication occurs in 30-40% of HSP children. It is the most serious complication in the chronic outcome. Objectives Objective of the study is to evaluate the possible risk factors of renal complications in our series of children with HSP. Moreover we have tried to determine the time of onset of renal involvement. Methods Retrospective study was conducted in children with HSP in our Department with follow-up of at least 24 months. We evaluated 66 children, 37 males and 29 females. We have considered as risk factors of renal complication the sex, the presence or history of allergy, the joint and intestinal involvement. Results 20/66 HSP children have showed renal involvement (RHSP). RHSP was more frequent in males (14/20: 70%) versus females (6/20: 30%). Among the 46 children without renal involvement 24 (52%) were male and 22 (48%) females. Our data show that the male has greater risk of developing renal complications (OR 2.13; 95% CI 0.69 to 6.54).Average age of onset of vasculitis is 75.5±24 months in the RHSP versus 72.1±33.6 months in HSP without renal involvement. There was no difference in joint (60% versus 63%) and/or bowel (50% versus 41%) involvement between the two groups. Allergic symptoms occurred in 15% of RHSP children versus 29% of HSP children without renal involvement. Renal involvement developed in 30% of cases at onset of HSP; in 60% within 10 days of the diagnosis, and in 90% within 6 months. Only two children had renal complication after 12 and 18 months from diagnosis. Six renal biopsies were performed: 3 at the onset of illness and 3 within ten days from HSP diagnosis. Cutaneous recurrences occurred more frequently in the HSP group without renal involvement (30%) than in RHSP (5%) (OR 8.3; 95% CI 1.01 to 68.33). Conclusions Our data showed that the male is the greater risk factor for renal complications in HSP patients. The renal involvement occurred mostly at onset and in the majority of cases within 6 months. In addition, the renal complication is more severe in the early days of onset of HSP as evidenced by the greater frequency of renal biopsies. We recommended to monitor carefully urine exam in the first 6 months from onset of vasculitis. Cutaneous relapses were rare in patients with RHSP, indicating a different pathogenetic mechanism and phenotypic expression between HSP patients. References Narchi H. Risk of long term renal impairment and duration of follow up recommended for Henoch-Schonlein purpura with normal or minimal urinary findings: a systematic review. Arch Dis Child 2005;90:916–920. Disclosure of Interest None declared

Acute urine retention can be the first clinical sign of a rabdomyosarcoma (RMS) of bladder and prostate. This is particularly evident in the age group comprised between 2 and 4 years. The Authors report their experience on three cases of 2 years old males admitted for acute urine retention. One case was diagnosed to have an prostate RMS, the other two a RMS of the bladder. The prostate RMS refused the operation dying 2 years after operation. Of the two cases of RMS of the bladder, one was treated successfully by polychemotherapy treatment, the second, after polychemotherapy underwent a partial cystectomy. The Authors conclude affirming the importance of a ultrasonography of the lower urinary tract in all patients with acute retention of urine, since this could be the first sign of a RMS of prostate or bladder.