Rauen K.A.,University of California at San Francisco |
Tidyman W.E.,University of California at San Francisco |
Estep A.L.,University of California at San Francisco |
Sampath S.,Health Science Center |
And 4 more authors.
American Journal of Medical Genetics, Part A | Year: 2010
Cardio-facio-cutaneous (CFC) syndrome is one of the RASopathies and is caused by alteration of activity through the Ras/ mitogen-activated protein kinase (MAPK) pathway due to heterozygous de novo mutations in protein kinases BRAF, MEK1, or MEK2. CFC is a rare multiple congenital anomaly disorder in which individuals have characteristic dysmorphic features, cardiac defects, ectodermal anomalies and developmental delay.We report a 71/2-month-old boy with a clinical diagnosis of CFC. Bidirectional sequence analysis of MEK2 revealed a novel c.383C→Atransversion in exon 3 resulting in a nonsynonymous missense substitution, p.P128Q. Other family members, including the proband's mother and half-sibling, displayed phenotypic features of CFC and were also screened for the MEK2 mutation identified in the proband. Sorting Intolerant From Tolerant (SIFT) analysis determined the novel MEK2 p.P128Q to be deleterious. To corroborate the functional alteration of the novel mutant protein, transient transfection of HEK 293T cells with subsequent Western analysis was used to demonstrate increased kinase activity, as measured by ERK phosphorylation. This first reported case of a vertically transmitted functional CFC MEK mutation further expands our understanding of germline mutations within the Ras/MAPK pathway. © 2010 Wiley-Liss, Inc.
Schaefer B.,University of Heidelberg |
Schaefer F.,University of Heidelberg |
Wittmer D.,University of Heidelberg |
Engelmann G.,University of Heidelberg |
And 3 more authors.
Pediatric Nephrology | Year: 2012
Background Cholestatic pruritus may severely compromise quality of life. The Molecular Adsorbents Recirculating System (MARS) allows removal of pruritogenic substances without exposure to foreign proteins. Pediatric data, however, are scant. Methods We retrospectively analyzed the efficacy of MARS in three boys with severe cholestatic pruritus. They received a total of 135 MARS sessions during 8, 4, and 13 months prior to liver transplantation. Total serum bilirubin and bile acids were monitored, and pruritus was assessed by a numerical rating scale (NRS 0 = no pruritus, 10 = maximal pruritus). Results MARS sessions were initially performed three times weekly at a mean duration of 6.3±1.4 h. Sessions could be reduced to once weekly and once every other week in two patients. Pre-MARS plasma bile acid concentrations averaged 207±67 μmol/l. They declined to 67± 9%, 48±3%, 38±14%, and 37±5% of baseline within 2, 4, 6 and 8 h of therapy, respectively (all p<0.05). The average interdialytic increase of plasma bile acids was 34±33 μmol/ l per day. Mean NRS score decreased from 6.5±2.3 to 3.3± 2.9 (p<0.01). Skin lesions from itching disappeared. All MARS treatments were well tolerated. Conclusion MARS dialysis substantially reduces cholestatic pruritus in children refractory to pharmacological treatment. © IPNA 2012.
Thimm E.,Heinrich Heine University Dusseldorf |
Schmidt L.E.,Heinrich Heine University Dusseldorf |
Heldt K.,Center for Pediatric and Adolescent Medicine |
Spiekerkoetter U.,University Hospital Freiburg
Journal of Inherited Metabolic Disease | Year: 2013
Aim of the study was the evaluation of health-related quality of life (HRQoL) and the detection of deviant behavior in early-treated children and adolescents with PKU in comparison with healthy peers. Special focus was laid on the impact of compliance with treatment as defined by the national recommendations on HRQoL. Our investigation in 50 children and adolescents and their parents for the first time demonstrates that despite an overall normal HRQoL in our PKU patient collective, parents are concerned about performance in school especially when phenylalanine concentrations in their children are mainly above the therapeutic range. Adherence to target phenylalanine concentrations ameliorated markedly in patients above 10 years in comparison to younger patients due to relaxed treatment recommendations. Interestingly, this alleged improvement in metabolic control has an impact on the parent assessed but not on the patient assessed appraisal of HRQoL. However, a positive correlation between poor metabolic control and conduct problems was identified by patients' self-assessment. In conclusion, lacking adherence to the strict treatment recommendations in infancy results in significant concern about school success and success in life in parents of PKU patients. With relaxation of dietary phenylalanine restriction at 10 years of age, these concerns diminish. © 2012 SSIEM and Springer Science+Business Media Dordrecht.
Schmitt C.P.,Center for Pediatric and Adolescent Medicine |
Bakkaloglu S.A.,Gazi University |
Klaus G.,diatric Kidney Center |
Schroder C.,Gelre Hospital
Pediatric Nephrology | Year: 2011
The purpose of this article is to provide recommendations on the choice of peritoneal dialysis (PD) fluids in children by the European Pediatric Dialysis Working Group. The literature on experimental and clinical studies with PD solutions in children and adults was analyzed together with consensus discussions within the group. A grading was performed based on the international KDIGO nomenclature and methods. The lowest glucose concentration possible should be used. Icodextrin may be applied once daily during the long dwell, in particular in children with insufficient ultrafiltration. Infants on PD are at risk of ultrafiltration-associated sodium depletion, while anuric adolescents may have water and salt overload. Hence, the sodium chloride balance needs to be closely monitored. In growing children, the calcium balance should be positive and dialysate calcium adapted according to individual needs. Limited clinical experience with amino acid-based PD fluids in children suggests good tolerability. The anabolic effect, however, is small; adequate enteral nutrition is preferred. CPD fluids with reduced glucose degradation products (GDP) content reduce local and systemic toxicity and should be preferred whenever possible. Correction of metabolic acidosis is superior with pH neutral bicarbonate-based fluids compared with singlechamber, acidic, lactate-based solutions. Prospective comparisons of low GDP solutions with different buffer compositions are still few, and firm recommendations cannot yet be given, except when hepatic lactate metabolism is severely compromised. © IPNA 2010.
Kager L.,St. Anna Childrens Hospital |
Zoubek A.,St. Anna Childrens Hospital |
Dominkus M.,Vienna University Hospital |
Lang S.,Vienna University Hospital |
And 6 more authors.
Cancer | Year: 2010
BACKGROUND: This study was conducted to investigate presentation, treatment, and outcome in very young children with osteosarcoma. METHODS: The authors retrospectively analyzed the data of 2706 consecutive COSS patients with newly diagnosed osteosarcoma and identified 28 (1.0%) patients aged younger than 5 years at diagnosis. Demographic, diagnostic, tumor, treatment-related variables, response, and survival data were analyzed. RESULTS: Of the 28 preschoolers, 27 presented with high-grade central osteosarcoma of an extremity, and 1 had a secondary osteosarcoma of the orbit. This analysis focused on the 27 patients with extremity tumors. The size of the primary was large (≥one-third of the involved bone) in 20 of 27 patients. Primary metastases were detected in 4 of 27 children. All patients received multiagent chemotherapy, and 11 of 18 analyzed tumors responded well (>90% necrosis) to neoadjuvant chemotherapy. Limb-sparing surgery was performed in 9 cases, ablative procedures were performed in 15, and, in 3 cases, no local surgery was performed. With a median follow-up of 4 years (6.2 years for survivors), 13 patients were alive. Four patients never achieved a complete remission, and 11 developed recurrences; 14 of these 15 patients died. Five-year overall and event-free survival probabilities were 51% (standard error of the mean [SE], 10%) and 48% (SE, 10%). Better survival was correlated with good response to chemotherapy and later time period of diagnosis. CONCLUSIONS: Osteosarcoma is extremely rare in preschool children. These patients often have large tumors that may require mutilating resections. Prognosis is in the range of that reported for older patients. © 2010 American Cancer Society.