Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?

Background: Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown.

Methods: We reviewed the records of 65 patients with SMARCAL1 mutations.

Idiopathic midaortic syndrome: normalization of blood pressure on medication.

Midaortic syndrome (MAS) is a rare, idiopathic condition in children usually presenting with severe hypertension. We report a case of a 13-year-old girl who presented with severe hypertension (200/110 mmHg) associated with renal artery stenosis and normal renal function (creatinine clearance 110 ml/min/1.73m(2)).

Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II Bayesian trial.

Mycophenolate mofetil (MMF) has emerged as a new therapeutic option in steroid-dependent nephrotic syndrome (SDNS). We conducted a phase II Bayesian trial of MMF in children with SDNS. Phase II trials, usually single-arm studies, investigate the effect of new treatments.

Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy that associates, in 70% of cases, with genetic or acquired disorders leading to dysregulation of the alternative pathway of complement. Autoantibody directed against Factor H causes at least 6% to 10% of aHUS cases, but only a few clinical reports are available. Here, we describe the clinical, biologic, genetic features, treatment, and outcome of 45 patients who presented with aHUS associated with anti-FH autoantibody.

Population pharmacokinetics and Bayesian estimator of mycophenolic acid in children with idiopathic nephrotic syndrome.

Aims: To develop a population pharmacokinetic model for mycophenolic acid (MPA) in children with idiopathic nephrotic syndrome (INS) treated with mycophenolate mofetil (MMF), identify covariates that explain variability and determine the Bayesian estimator of the area under the concentration-time curve over 12 h (AUC(0-12)).

Methods: The pharmacokinetic model of MMF was described from 23 patients aged 7.4 +/- 3.

Population pharmacokinetics and pharmacogenetics of mycophenolic acid following administration of mycophenolate mofetil in de novo pediatric renal-transplant patients.

The objective was to develop a population pharmacokinetic-pharmacogenetic model of mycophenolic acid following administration of mycophenolate mofetil (MMF) in de novo pediatric renal-transplant patients and identify factors that explain variability. The pharmacokinetic samples were collected from 89 de novo pediatric renal-transplant patients treated with MMF and studied during the first 60 postoperative days. All patients were genotyped for UGT1A8-A9, UGT2B7, and ABCC2.

Schimke immunoosseous dysplasia: defining skeletal features.

Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by prominent spondyloepiphyseal dysplasia, T cell deficiency, and focal segmental glomerulosclerosis. Biallelic mutations in swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD, but approximately half of patients referred for molecular studies do not have detectable mutations in SMARCAL1. We hypothesized that skeletal features distinguish between those with or without SMARCAL1 mutations.

Long-term results of rhGH treatment in children with renal failure: experience of the French Society of Pediatric Nephrology.

Few publications have described the long-term effects of recombinant human growth hormone (rhGH) in uremic patients. This study reports the results of rhGH therapy at the end of treatment and at adult age in 178 French patients. At enrollment, 63 patients were under conservative treatment (CT), 40 under hemodialysis (HD), and 75 had a functioning renal transplant (RT).

Darbepoetin, effective treatment of anaemia in paediatric patients with chronic renal failure.

Darbepoetin alpha (DA) is a unique long-acting treatment for anaemia in patients with chronic renal failure (CRF). This study assessed the mean dose of DA to achieve and maintain haemoglobin (Hb) levels between 11 g/dl and 13 g/dl in CRF children aged 11 years to 18 years. This observational, prospective study was conducted in 39 patients treated with DA.

Schimke immunoosseous dysplasia: suggestions of genetic diversity.

Schimke immunoosseous dysplasia (SIOD), which is characterized by prominent spondyloepiphyseal dysplasia, T-cell deficiency, and focal segmental glomerulosclerosis, is a panethnic autosomal recessive multisystem disorder with variable expressivity. Biallelic mutations in switch/sucrose nonfermenting (swi/snf) related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD. However, among 72 patients from different families, we identified only 38 patients with biallelic mutations in the coding exons and splice junctions of the SMARCAL1 gene.

Recurrence of nephrotic syndrome after renal transplantation: influence of increased immunosuppression.

Recurrence of nephrotic syndrome after renal transplantation leads to graft loss within 1 year in 50-80% of patients who do not receive any specific treatment. Several treatment protocols have been proposed leading to long-term remission in 50-80% of patients. The aim of our study was to evaluate the efficiency of intensified immunosuppression, simultaneously including methylprednisolone pulses, cyclophosphamide, high-dose cyclosporine and plasma exchanges.

Association of migraine-like headaches with Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia (SIOD) is characterized by spondyloepiphyseal dysplasia, nephropathy, and T-cell deficiency. SIOD is caused by mutations in the putative chromatin remodeling protein SMARCAL1. We report an 8-year-old boy with SIOD and recurrent, severe, refractory migraine-like headaches.

Long-term follow-up of Epstein-Barr virus viremia in pediatric recipients of renal transplants.

The common observation of Epstein-Barr virus (EBV) viremia in pediatric recipients of renal transplants and the occurrence of an EBV-related pulmonary leiomyoma prompted us to intensify the follow-up of EBV infections from 1995 to October 2000. Follow-up included serology and detection of viral DNA in blood using a semi-quantitative nested polymerase chain reaction (PCR) and later a real-time PCR with higher sensitivity. The aim of this study was the early detection of primary infections or reactivations.

Sudden blindness caused by anterior ischemic optic neuropathy in 5 children on continuous peritoneal dialysis.

The authors report the occurrence of sudden blindness in 5 children (mean age, 32 months; range, 11 to 60) during continuous peritoneal dialysis regimen. All children presented with loss of light perception, visual fixation and ocular pursuit, and bilateral mydriasis unreactive to bright light. Fundoscopic examination found signs of anterior ischemic optic neuropathy with disc swelling, edema, and hemorrhages.

Final height in children with chronic renal failure who have not received growth hormone.

Final height (FH), growth velocity after 16 and 18 years of age, and factors predictive for FH were assessed in 60 patients (21-36 years old), whose chronic renal failure (CRF) started before the age of 16 years (28 girls and 32 boys). At 16 years of age, 22 had conservative treatment (CT, group A) and 38 end-stage renal failure [ESRF, group B, which includes 19 receiving hemodialysis (HD) and 19 with a functional renal transplant (RTx)]. None received recombinant human growth hormone (rhGH) treatment.

Transient hyperphosphatasemia after organ transplantation in children.

Transient, isolated hyperphosphatasemia is a rare, benign condition of childhood. Few cases have been described in transplant patients. We report six cases: three after liver transplantation and three after kidney transplantation.

Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele.