Belostotsky R.,Shaare Zedek Medical Center |
Seboun E.,University Pierre and Marie Curie |
Seboun E.,French Institute of Health and Medical Research |
Idelson G.H.,Shaare Zedek Medical Center |
And 13 more authors.
American Journal of Human Genetics | Year: 2010
Primary hyperoxaluria (PH) is an autosomal-recessive disorder of endogenous oxalate synthesis characterized by accumulation of calcium oxalate primarily in the kidney. Deficiencies of alanine-glyoxylate aminotransferase (AGT) or glyoxylate reductase (GRHPR) are the two known causes of the disease (PH I and II, respectively). To determine the etiology of an as yet uncharacterized type of PH, we selected a cohort of 15 non-PH I/PH II patients from eight unrelated families with calcium oxalate nephrolithiasis for high-density SNP microarray analysis. We determined that mutations in an uncharacterized gene, DHDPSL, on chromosome 10 cause a third type of PH (PH III). To overcome the difficulties in data analysis attributed to a state of compound heterozygosity, we developed a strategy of "heterozygosity mapping" - a search for long heterozygous patterns unique to all patients in a given family and overlapping between families, followed by reconstruction of haplotypes. This approach enabled us to determine an allelic fragment shared by all patients of Ashkenazi Jewish descent and bearing a 3 bp deletion in DHDPSL. Overall, six mutations were detected: four missense mutations, one in-frame deletion, and one splice-site mutation. Our assumption is that DHDPSL is the gene encoding 4-hydroxy-2-oxoglutarate aldolase, catalyzing the final step in the metabolic pathway of hydroxyproline. © 2010 The American Society of Human Genetics.
PubMed | Ospedale Regionale di Bellinzona, Pediatric Nephrology Unit, Klinikum der Stadt Ludwigshafen, University of Lausanne and University Hospital Berne
Type: Journal Article | Journal: European journal of pediatrics | Year: 2016
We report a novel homozygous missense mutation in the ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene in two consanguineous Turkish families associated with deafness, Fanconi syndrome (tubulopathy), microcephaly, mental and growth retardation. All three patients presented with transitory metabolic acidosis in the neonatal period and development of persistent renal de Toni-Debr-Fanconi-type tubulopathy, with subsequent rachitis, short stature, microcephaly, sensorineural hearing impairment, mild mental retardation and liver dysfunction. The novel missense mutation c.142A>G (p.M48V) in BCS1L is located at a highly conserved region associated with sorting to the mitochondria. Biochemical analysis revealed an isolated complex III deficiency in skeletal muscle not detected in fibroblasts. Native polyacrylamide gel electrophoresis (PAGE) revealed normal super complex formation, but a shift in mobility of complex III most likely caused by the absence of the BCS1L-mediated insertion of Rieske Fe/S protein into complex III. These findings expand the phenotypic spectrum of BCS1L mutations, highlight the importance of biochemical analysis of different primary affected tissue and underline that neonatal lactic acidosis with multi-organ involvement may resolve after the newborn period with a relatively spared neurological outcome and survival into adulthood.Mutation screening for BCS1L should be considered in the differential diagnosis of severe (proximal) tubulopathy in the newborn period. Mutations in BCS1L cause mitochondrial complex III deficiencies. Phenotypic presentations of defective BCS1L range from Bjornstad to neonatal GRACILE syndrome. What is New: Description of a novel homozygous mutation in BCS1L with transient neonatal acidosis and persistent de Toni-Debr-Fanconi-type tubulopathy. The long survival of patients with phenotypic presentation of severe complex III deficiency is uncommon.
Ammenti A.,University of Parma |
Cataldi L.,Catholic University Sacro Cuore |
Chimenz R.,Messina University |
Fanos V.,University of Cagliari |
And 9 more authors.
Acta Paediatrica, International Journal of Paediatrics | Year: 2012
We report the recommendations for the diagnosis, treatment, imaging evaluation and use of antibiotic prophylaxis in children with the first febrile urinary tract infection, aged 2 months to 3 years. They were prepared by a working group of the Italian Society of Pediatric Nephrology after careful review of the available literature and a consensus decision, when clear evidence was not available. Conclusion: These recommendations are endorsed by the Italian Society of Pediatric Nephrology. They can also be a tool of comparison with other existing guidelines in issues in which much controversy still exists. © 2011 The Author(s)/Acta Pædiatrica.
Poupalou A.,Pediatric Surgery unit |
Salomon R.,Nephrology Unit |
Boudjemline Y.,Cardiology Unit |
Allain-Launay E.,Pediatric Nephrology Unit |
And 2 more authors.
Pediatric Nephrology | Year: 2013
Background: Middle aortic syndrome (MAS) is a rare condition characterized by stenosis of the proximal abdominal aorta and the origin of the renal and digestive arteries. When medical therapy and interventional radiology fail to control threatening reno-vascular arterial hypertension (AHT), surgery is required and may need several interventions, which are usually delayed until late childhood. Case: We report on a 3-year-old girl with severe AHT (180/130 mmHg) caused by MAS. There was no evidence of generalized vascular disease or complications of AHT. AHT failed to respond to medical therapy (five drugs), endovascular dilatation, and stenting was considered unfeasible due to the complex multiple strictures. Surgery consisted of: Explantation of the two kidneys; aortic bypass between the lower thoracic and lower abdominal aorta using a prosthetic graft; reimplantation of the kidneys onto the normal iliac arteries. The post-operative course was uneventful. Owing to recurrent stenosis of the re-implanted renal arteries, endoluminal dilatations were performed 4 and 5 months after surgery. Two years after surgery, the child is alive and well, off anti-hypertensive therapy, with normal blood pressure. Conclusion: Mild aortic syndrome can be treated with a one-stage surgical repair with aorto-aortic bypass and bilateral auto-transplantation, even in young children. © 2013 IPNA.
PubMed | Arnaud Of Villeneuve Hospital, University of Nantes, Necker Hospital, University of Strasbourg and 4 more.
Type: | Journal: Pediatric nephrology (Berlin, Germany) | Year: 2016
Peritoneal dialysis (PD) remains the modality of choice in children, but there is no clear evidence to support a better outcome in children treated with PD. We aimed to assess factors that have an impact on the choice of dialysis modality in children and young adults in France and sought to determine the roles of medical factors and center practices.We included all patients aged <20years at the start of renal replacement therapy (RRT), recorded in the French RRT Registry between 2002 and 2013. Hierarchical logistic regression models were used to study the association between the patient/center characteristics and the probability of receiving PD as the first dialysis modality.We included 806 patients starting RRT in 177 centers, 23 of which were specialized pediatric centers. Six hundred and one patients (74.6%) started with hemodialysis (HD), whereas 205 (25.4%) started with PD. A greater probability of PD was found in younger children, whereas starting the treatment in an emergency setting was associated with a low use of PD. We found a significant variability among centers that accounted for 43% of the total variability. The probability of PD was higher in adult centers and was proportional to the rate of PD in the center.Center practices are a major factor in the choice of dialysis modality. This raises concerns about patient and family choices and to what extent doctors may influence the final decision. Further pediatric studies focusing on childrens and parents wishes are needed to provide care as close as possible to patients and families expectations.
Bozzini G.,University of Milan |
Lunelli L.,University of Milan |
Berlingheri M.,Pediatric Nephrology Unit |
Groppali E.,Pediatric Nephrology Unit |
Carmignani L.,University of Milan
Andrologia | Year: 2013
Microlithiasis of the epididymis is a rare ultrasound finding in the general population, but the incidence of calcifications in various organs of patients with end-stage renal disease (ESRD) is extremely high. The aim of this study was to describe epididymal microlithiasis in 22 previously dialysed patients who received kidney transplantations at a median age of 19 years (range 9-30). The patients underwent scrotum ultrasonography, semen analysis and laboratory tests (renal function, sexual hormones, Ca, P and PTH) and were administered the International Index of Erectile Function questionnaire. Seventeen presented calcifications of the epididymis, two of whom had concomitant testicular calcifications; a further three patients had isolated testicular calcifications without epididymis involvement. It was not possible to investigate the fertility of all of the patients but 12 of the 13 whose semen was analysed showed abnormalities: five were azoospermic and seven oligospermic with various degrees of morphological anomalies. To the best of our knowledge, these are the first published data concerning the prevalence of epididymal calcifications in young dialysed patients undergoing renal transplantation. Epididymal microlithiasis and infertility were common findings and so performing a spermiogram and preserving semen before ESRD for future paternity may be good advice in this selected population. © 2012 Blackwell Verlag GmbH.
Radhakrishnan N.,Sir Ganga Ram Hospital |
Yadav S.P.,Sir Ganga Ram Hospital |
Sachdeva A.,Sir Ganga Ram Hospital |
Pruthi P.K.,Pediatric Nephrology Unit |
And 4 more authors.
Journal of Pediatric Hematology/Oncology | Year: 2011
Heme oxygenase - 1 (HO-1) is a stress-induced enzyme that catalyses the oxidation of heme to biliverdin. The primary deficiency of this enzyme has been shown in HO-1 knockout mice, and is characterized by intrauterine death and chronic inflammation. The first case of human HO-1 deficiency was reported in 1999. Human HO-1 deficiency has been observed to involve the endothelial cells more severely, resulting in hemolysis and disseminated intravascular coagulation. We report another case of human HO-1 deficiency in a young girl with congenital asplenia, who presented with severe hemolysis, inflammation, nephritis, which was refractory to therapy with corticosteroids, cyclophosphamide, and rituximab. Copyright © 2011 by Lippincott Williams & Wilkins.
Edefonti A.,Pediatric Nephrology Unit |
Tel F.,Pediatric Nephrology Unit |
Testa S.,Pediatric Nephrology Unit |
De Palma D.,Ospedale di Circolo
Seminars in Nuclear Medicine | Year: 2014
According to the literature, febrile urinary tract infections (UTIs) are among the most common severe bacterial infections occurring in childhood, with potential serious long-term consequences. In recent years, there have been significant developments in our understanding of the pathophysiology and clinical and laboratory issues of febrile UTIs. Studies are focusing on the role of predisposing host factors related to genes regulating immune response, inflammation and fibrosis in the development of acute renal damage and subsequent processes leading to renal scars. All the available guidelines underline the importance of a correct diagnosis of febrile UTI to allow a more rational use of antibiotics and imaging. As a consequence, a shift from aggressive imaging studies to a more restrictive and targeted approach has been recently observed. Regarding the prognosis of febrile UTI, the introduction of prenatal ultrasound studies revealed that a great portion of the alterations at imaging (and thus of the clinical complications), previously attributed to postinfection scarring, were because of congenital kidney and urinary tract abnormalities. Although the long-term consequences of febrile UTIs are difficult to ascertain, it seems that children with febrile UTI, normal renal function and normal kidneys at start present a very low risk of developing decreased renal function or hypertension during follow-up. However, high body temperature and high procalcitonin levels during the acute phase of disease, which are indicative of severe inflammation, and the finding of renal scarring on imaging with DMSA scintigraphy 6 months after febrile UTI, together with the detection of congenital kidney and urinary tract abnormalities, indicate "kidney at risk" in UTI. © 2014 Elsevier Inc.
Chernin G.,University of Michigan |
Vega-Warner V.,University of Michigan |
Schoeb D.S.,University of Michigan |
Heeringa S.F.,University of Michigan |
And 6 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2010
Background and objectives: The risk of developing Wilms tumor (WT) can be present or absent in patients with nephrotic syndrome (NS) caused by WT1 mutations. Here, the genotype/phenotype correlation regarding the outcome and risk for WT in 52 patients from 51 families with NS due to WT1 mutations is described. Design, setting, participants, & measurements: This study followed 19 patients with mutations in intron 9 splice donor site (KTS mutations), 27 patients with missense mutations, 4 patients with nonsense mutations, 1 patient with a splice site mutation in intron 8, and 1 patient with a deletion. Results: Twenty-four different WT1 mutations were detected. Sixteen of the 19 patients with KTS mutations were females. These patients had isolated NS if karyotype was 46,XX and Frasier syndrome if karyotype was 46,XY. Patients with KTS mutations presented at a significantly older age and with a slower progression toward chronic kidney disease (CKD) stage 5, compared with missense mutations. Patients with nonsense mutations presented initially with WT. Six patients with missense mutations developed WT after the diagnosis of NS (interval-range from NS onset to WT of 0.1 to 1.4 years). Conclusions: (1) KTS mutations cause isolated NS with absence of WT in 46,XX females. (2) KTS mutations cause Frasier syndrome with gonadoblastoma risk in 46,XY phenotypic females. (3) KTS mutations cause NS with a slower progression when compared with missense mutations. (4) Missense mutations can occur with and without WT. (5) WT1 analysis is important in young patients with NS for early detection and tumor prophylaxis. Copyright © 2010 by the American Society of Nephrology.
Magen D.,Pediatric Nephrology Unit |
Magen D.,Laboratory of Molecular Medicine |
Magen D.,Technion - Israel Institute of Technology |
Berger L.,Laboratory of Molecular Medicine |
And 10 more authors.
New England Journal of Medicine | Year: 2010
We describe two siblings from a consanguineous family with autosomal recessive Fanconi's syndrome and hypophosphatemic rickets. Genetic analysis revealed a homozygous in-frame duplication of 21 bp in SLC34A1, which encodes the renal sodium-inorganic phosphate cotransporter NaPi-IIa, as the causative mutation. Functional studies in Xenopus laevis oocytes and in opossum kidney cells indicated complete loss of function of the mutant NaPi-IIa, resulting from failure of the transporter to reach the plasma membrane. These findings show that disruption of the human NaPi-IIa profoundly impairs overall renal phosphate reabsorption and proximal-tubule function and provide evidence of the critical role of NaPi-IIa in human renal phosphate handling. Copyright © 2010 Massachusetts Medical Society.