Center for Paediatric and Adolescent Medicine

Heidelberg, Germany

Center for Paediatric and Adolescent Medicine

Heidelberg, Germany

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Forbes T.A.,Nottingham Childrens Hospital | Watson A.R.,Nottingham Childrens Hospital | Zurowska A.,University of Gdansk | Shroff R.,Great Ormond Street Hospital for Children | And 12 more authors.
Pediatric Nephrology | Year: 2014

Background There is increasing focus on the problems involved in the transition and transfer of young adult patients from paediatric to adult renal units. This situation was addressed by the 2011 International Pediatric Nephrology Association/International Society of Nephrology (IPNA/ISN) Consensus Statement on transition. Methods We performed a survey of transition practices of 15 paediatric nephrology units across Europe 2 years after publication of the consensus statement. Results Two thirds of units were aware of the guidelines, and one third had integrated them into their transition practice. Forty-seven per cent of units transfer five or fewer patients with chronic kidney disease (CKD) stage 5 per year to a median of five adult centres, with higher numbers of CKD stages 2-4 patients. Seventy-three per cent of units were required by the hospital or government to transfer patients by a certain age. Eighty per cent of units commenced transition planning after the patient turned 15 years of age and usually within 1-2 years of the compulsory transfer age. Forty-seven per cent of units used a transition or transfer clinic. Prominent barriers to effective transition were patient and parent attachment to the paediatric unit and difficulty in allowing the young person to perform self-care. Conclusions Whereas awareness of the consensus statement is suboptimal, it has had some impact on practice. Adult nephrologists receive transferred patients infrequently, and the process of transition is introduced too late by paediatricians. Government- and hospital-driven age-based transfer policies distract focus from the achievement of competencies in self care. Variable use of transition clinics, written patient information and support groups is probably due to economic and human-resource limitations. The consensus statement provides a standard for evolving and evaluating transition policies jointly agreed upon by paediatric and adult units. © 2014 IPNA.


Welford R.W.D.,Actelion Pharmaceuticals | Garzotti M.,Actelion Pharmaceuticals | Lourenco C.M.,Hospital Das Clinicas Of Ribeirao Preto | Mengel E.,Center for Paediatric and Adolescent Medicine | And 6 more authors.
PLoS ONE | Year: 2014

Niemann-Pick disease type C (NP-C) is a devastating, neurovisceral lysosomal storage disorder which is characterised by variable manifestation of visceral signs, progressive neuropsychiatric deterioration and premature death, caused by mutations in the NPC1 and NPC2 genes. Due to the complexity of diagnosis and the availability of an approved therapy in the EU, improved detection of NP-C may have a huge impact on future disease management. At the cellular level dysfunction or deficiency of either the NPC1 or NPC2 protein leads to a complex intracellular endosomal/lysosomal trafficking defect, and organ specific patterns of sphingolipid accumulation. Lysosphingolipids have been shown to be excellent biomarkers of sphingolipidosis in several enzyme deficient lysosomal storage disorders. Additionally, in a recent study the lysosphingolipids, lysosphingomyelin (SPC) and glucosylsphingosine (GlcSph), appeared to be elevated in the plasma of three adult NP-C patients. In order to investigate the clinical utility of SPC and GlcSph as diagnostic markers, an in-depth fit for purpose biomarker assay validation for measurement of these biomarkers in plasma by liquid chromatography-tandem mass spectrometry was performed. Plasma SPC and GlcSph are stable and can be measured accurately, precisely and reproducibly. In a retrospective analysis of 57 NP-C patients and 70 control subjects, median plasma SPC and GlcSph were significantly elevated in NP-C by 2.8-fold and 1.4-fold respectively. For miglustat-nälve NP-C patients, aged 2-50 years, the area under the ROC curve was 0.999 for SPC and 0.776 for GlcSph. Plasma GlcSph did not correlate with SPC levels in NP-C patients. The data indicate excellent potential for the use of lysosphingomyelin in NP-C diagnosis, where it could be used to identify NP-C patients for confirmatory genetic testing. © 2014 Welford et al.


Arngrimsson R.,University of Iceland | Barbey F.,University of Lausanne | Cecchi F.,University of Florence | Deegan P.B.,University of Cambridge | And 24 more authors.
Orphanet Journal of Rare Diseases | Year: 2015

Introduction: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD. Methods: A Delphi procedure was conducted with an online survey (n∈=∈28) and a meeting (n∈=∈15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with 75% agreement and no disagreement. Results: For classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of 16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73 m2) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped. Conclusion: The recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations. © 2015 Biegstraaten et al.; licensee BioMed Central.


PubMed | University of Turku, University of Zürich, The Childrens Memorial Health Institute, General Hospital Slovenj Gradec and 21 more.
Type: | Journal: Orphanet journal of rare diseases | Year: 2015

Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD.A Delphi procedure was conducted with an online survey (n=28) and a meeting (n=15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with 75% agreement and no disagreement.For classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of 16years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73m(2)) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1year. In those with cognitive decline of any cause, or lack of response for 1year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped.The recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations.


Watson A.R.,Nottingham Childrens Hospital | Hayes W.N.,Nottingham Childrens Hospital | Vondrak K.,University Hospital Motol | Ariceta G.,Hopital Cruces | And 11 more authors.
Pediatric Nephrology | Year: 2013

Background: Many factors may impact upon choice of renal replacement therapy (RRT) for children and adolescents, including patient and family choice, patient size and distance from the renal centre as well as logistic issues such as facilities and staffing at the unit. We report a survey of factors influencing treatment choice in 14 European paediatric nephrology units. Methods: A questionnaire was developed by consensus and completed by 14 members of the European Paediatric Dialysis Working Group on facilities, staffing and family assessments impacting on choice of therapy as well as choice of therapy for 97 patients commencing initial RRT in 2011. Results: All units offered all modalities of RRT, but there were limitations for pre-emptive transplantation (PET) and largely adult surgical dependence for creation of arteriovenous fistulae and transplantation. The average waiting time for a deceased donor kidney was 18.5 (range 3-36) months. Full time dietetic support was available in six of the 14 units. There was no social worker, psychology, play therapy or teaching support in three, two, seven and four units, respectively. Assessment by other members of the multidisciplinary team and home visits before choice of therapy was carried out in 50 % of units, and although all patients were discussed at team meetings, the medical opinion predominated. In terms of types of RRT, 50 % of patients were commenced on chronic peritoneal dialysis (PD), 34 % on haemodialysis (HD) and 16 % underwent pre-emptive transplantation (PET). Chronic PD predominated in patients aged <5 years and HD predominated in those aged >10 years. Patient and family choice and age or size of patient were predominant factors in choice of therapy with a predictable decline in renal function favouring PET and social factors HD. Conclusions: Chronic peritoneal dialysis predominated as primary choice of RRT, especially in younger children. The PET rates remain low. The influence of surgeons predominanted, and national transplant rules may be significant. Most units had insufficient multiprofessional support, which may impact upon initial choice of therapy as well as sustaining families through RRT. © 2013 IPNA.


Gramer G.,Center for Paediatric and Adolescent Medicine | Wolf N.I.,VU University Amsterdam | Vater D.,Center for Paediatric and Adolescent Medicine | Bast T.,Epilepsy Center Kork | And 4 more authors.
Neuropediatrics | Year: 2012

Background: Typical cases of glucose transporter-1 deficiency syndrome (GLUT1-DS) present with early-onset epilepsy. We report symptoms, diagnostic results, and effects of therapy in two patients diagnosed with GLUT1-DS at the age of 10 and 15 years, respectively. Patients: Patient 1: After four cerebral seizures in the first 2 years of life the patient was seizure-free but showed a complexmovement disorder, expressive speech disorder, and mental retardation. Ratio of cerebrospinal fluid (CSF) to blood glucose was 0.41 (reference range 0.65 ± 0.1), molecular genetic testing confirmed GLUT1 deficiency with the novel pathogenic mutation c.1377dupC (p.Phe460LeufsX3) in the SLC2A1 gene. Following 9 months of ketogenic diet started at the age of 10 years, there was distinct improvement of speech and movement disorder. Patient 2 showed pharmacorefractive epilepsy, mental retardation, and a mild movement disorder. At the age of 15 years, extensive intake of food with high fat content was observed. Ratio of CSF to blood glucose was 0.41 (reference range 0.65 ± 0.1). The pathogenic mutation c.634C>T (p.Arg212Cys) was found in the SLC2A1 gene. Conclusion: Self-induced high-fat diet can be a hint toward GLUT1-DS. Ketogenic diet can be beneficial even when started in late childhood, although it may take several months to achieve a positive effect. Copyright © 2012 by Thieme Medical Publishers, Inc.


Gramer G.,Center for Paediatric and Adolescent Medicine | Haege G.,Center for Paediatric and Adolescent Medicine | Langhans C.-D.,Center for Paediatric and Adolescent Medicine | Schuhmann V.,Center for Paediatric and Adolescent Medicine | And 2 more authors.
Prostaglandins Leukotrienes and Essential Fatty Acids | Year: 2016

Background Patients with phenylketonuria have been reported to be deficient in long-chain polyunsaturated fatty acids (LCPUFAs). It has been postulated that good compliance with the dietary regimen negatively influences LCPUFA status. Methods In 36 patients with phenylketonuria and 18 age-matched healthy control subjects LCPUFA-levels in plasma phospholipids and cholesteryl esters, erythrocyte phosphatidylcholine and phosphatidylethanolamine were evaluated. Results Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels did not differ significantly between patients and control subjects in plasma and erythrocyte fractions. There was a significant negative correlation between SDS (standard deviation) scores of DHA-levels in erythrocyte parameters from the respective age-matched control group and patients’ concurrent and long-term phenylalanine levels for erythrocyte phosphatidylethanolamine and erythrocyte phosphatidylcholine. Patients with lower (higher) phenylalanine levels had positive (negative) DHA-SDS. Conclusion In contrast to previous reports we did not find lower LCPUFA-levels in patients with phenylketonuria compared to age-matched healthy control subjects. Good dietary control was associated with better LCPUFA status. © 2016 Elsevier Ltd


PubMed | Center for Paediatric and Adolescent Medicine
Type: | Journal: Prostaglandins, leukotrienes, and essential fatty acids | Year: 2016

Patients with phenylketonuria have been reported to be deficient in long-chain polyunsaturated fatty acids (LCPUFAs). It has been postulated that good compliance with the dietary regimen negatively influences LCPUFA status.In 36 patients with phenylketonuria and 18 age-matched healthy control subjects LCPUFA-levels in plasma phospholipids and cholesteryl esters, erythrocyte phosphatidylcholine and phosphatidylethanolamine were evaluated.Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels did not differ significantly between patients and control subjects in plasma and erythrocyte fractions. There was a significant negative correlation between SDS (standard deviation) scores of DHA-levels in erythrocyte parameters from the respective age-matched control group and patients concurrent and long-term phenylalanine levels for erythrocyte phosphatidylethanolamine and erythrocyte phosphatidylcholine. Patients with lower (higher) phenylalanine levels had positive (negative) DHA-SDS.In contrast to previous reports we did not find lower LCPUFA-levels in patients with phenylketonuria compared to age-matched healthy control subjects. Good dietary control was associated with better LCPUFA status.


PubMed | Center for Paediatric and Adolescent Medicine
Type: Case Reports | Journal: Neuropediatrics | Year: 2012

Typical cases of glucose transporter-1 deficiency syndrome (GLUT1-DS) present with early-onset epilepsy. We report symptoms, diagnostic results, and effects of therapy in two patients diagnosed with GLUT1-DS at the age of 10 and 15 years, respectively.Patient 1: After four cerebral seizures in the first 2 years of life the patient was seizure-free but showed a complex movement disorder, expressive speech disorder, and mental retardation. Ratio of cerebrospinal fluid (CSF) to blood glucose was 0.41 (reference range 0.65 0.1), molecular genetic testing confirmed GLUT1 deficiency with the novel pathogenic mutation c.1377dupC (p.Phe460LeufsX3) in the SLC2A1 gene. Following 9 months of ketogenic diet started at the age of 10 years, there was distinct improvement of speech and movement disorder. Patient 2 showed pharmacorefractive epilepsy, mental retardation, and a mild movement disorder. At the age of 15 years, extensive intake of food with high fat content was observed. Ratio of CSF to blood glucose was 0.41 (reference range 0.65 0.1). The pathogenic mutation c.634C>T (p.Arg212Cys) was found in the SLC2A1 gene.Self-induced high-fat diet can be a hint toward GLUT1-DS. Ketogenic diet can be beneficial even when started in late childhood, although it may take several months to achieve a positive effect.

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