Newborn screening (NBS) programmes are essential in the diagnosis of inherited metabolic diseases (IMDs) and for access to disease modifying treatment. Most European countries follow the World Health Organisation (WHO) criteria to determine which disorders are appropriate for screening at birth; however, these criteria are interpreted and implemented by individual countries differently, creating disparities. Advances in research and diagnostics, together with the promise of new treatments, offer new possibilities to accelerate the expansion of evidence-based screening programmes. A novel and robust algorithm was built to objectively assess and prioritise IMDs for inclusion in NBS programmes. The Wilson and Jungner classic screening principles were used as a foundation to develop individual and measurable criteria. The proposed algorithm is a point-based system structured upon three pillars: condition, screening, and treatment. The algorithm was tested by applying the six IMDs currently approved in the United Kingdom NBS programme. The algorithm generates a weight-based score that could be used as the first step in the complex process of evaluating disorders for inclusion on NBS programmes. By prioritising disorders to be further evaluated, individual countries are able to assess the economic, societal and political aspects of a potential screening programme.
To avoid potentially severe outcomes, phenylketonuria (PKU) must be detected as soon as possible after birth and managed with life-long treatment. A questionnaire-based survey was performed to document diagnosis and management practices for PKU in a region of Southern and Eastern Europe. Prevalence and management data were obtained from 37/59 (63 %) centres within 19/22 (86 %) contacted countries (N = 8600 patients). The main results' analysis was based on completed questionnaires obtained from 31 centres (53 %) within 15 countries (68 %). A median of 10 % of patients per centre had been diagnosed after the newborn period. Metabolic dieticians and specialised adult PKU clinics were lacking in 36 and 84 % of centres, respectively. In 26 % of centres, treatment initiation was delayed until >15 days of life. Blood phenylalanine (Phe) thresholds to start treatment and upper Phe targets were inconsistent across centres. Ten percent of centres reported monitoring Phe every 2 weeks for pregnant women with PKU, which is insufficient to minimise risk of neonatal sequalae. Sapropterin dihydrochloride treatment was available in 48 % of centres, with 24-h responsiveness tests most common (36 %). Only one centre among the five countries lacking newborn screening provided a completed questionnaire., Conclusion: Targeted efforts by health care professionals and governments are needed to optimise diagnostic and management approaches for PKU in Southern and Eastern Europe."What is Known"• PKU must be detected early and optimally managed throughout life to avoid poor outcomes, yet newborn screening is not universal and diagnostic and management practices for PKU are known to vary widely between different centres and countries. • Targeted efforts by health care professionals and governments are needed to optimise diagnostic and management approaches. "What is New"• PKU management practices are documented in 19 South and Eastern European countries indicating a heterogeneous situation across the region. • Key areas for improvement identified in surveyed centres include a need for comprehensive screening in all countries, increased number of metabolic dietitians and specialised adult PKU clinics, delayed time to treatment initiation, appropriate Phe thresholds, Phe targets and monitoring frequencies, and universal access to currently available treatment options.
In: Gizewska , M , MacDonald , A , Belanger-Quintana , A , Burlina , A , Cleary , M , Coskun , T , Feillet , F , Muntau , A C , Trefz , F K , van Spronsen , F J & Blau , N 2016 , ' Diagnostic and management practices for phenylketonuria in 19 countries of the South and Eastern European Region : survey results ' , European Journal of Pediatrics , vol. 175 , no. 2 , pp. 261-272 . https://doi.org/10.1007/s00431-015-2622-5 ; ISSN:0340-6199
To avoid potentially severe outcomes, phenylketonuria (PKU) must be detected as soon as possible after birth and managed with life-long treatment. A questionnaire-based survey was performed to document diagnosis and management practices for PKU in a region of Southern and Eastern Europe. Prevalence and management data were obtained from 37/59 (63 %) centres within 19/22 (86 %) contacted countries (N = 8600 patients). The main results' analysis was based on completed questionnaires obtained from 31 centres (53 %) within 15 countries (68 %). A median of 10 % of patients per centre had been diagnosed after the newborn period. Metabolic dieticians and specialised adult PKU clinics were lacking in 36 and 84 % of centres, respectively. In 26 % of centres, treatment initiation was delayed until > 15 days of life. Blood phenylalanine (Phe) thresholds to start treatment and upper Phe targets were inconsistent across centres. Ten percent of centres reported monitoring Phe every 2 weeks for pregnant women with PKU, which is insufficient to minimise risk of neonatal sequalae. Sapropterin dihydrochloride treatment was available in 48 % of centres, with 24-h responsiveness tests most common (36 %). Only one centre among the five countries lacking newborn screening provided a completed questionnaire. Conclusion: Targeted efforts by health care professionals and governments are needed to optimise diagnostic and management approaches for PKU in Southern and Eastern Europe.
Abstract Urea cycle disorders (UCDs) are inborn errors of ammonia detoxification/arginine synthesis due to defects affecting the catalysts of the Krebs-Henseleit cycle (five core enzymes, one activating enzyme and one mitochondrial ornithine/citrulline antiporter) with an estimated incidence of 1:8.000. Patients present with hyperammonemia either shortly after birth (~50%) or, later at any age, leading to death or to severe neurological handicap in many survivors. Despite the existence of effective therapy with alternative pathway therapy and liver transplantation, outcomes remain poor. This may be related to underrecognition and delayed diagnosis due to the nonspecific clinical presentation and insufficient awareness of health care professionals because of disease rarity. These guidelines aim at providing a trans-European consensus to: guide practitioners, set standards of care and help awareness campaigns. To achieve these goals, the guidelines were developed using a Delphi methodology, by having professionals on UCDs across seven European countries to gather all the existing evidence, score it according to the SIGN evidence level system and draw a series of statements supported by an associated level of evidence. The guidelines were revised by external specialist consultants, unrelated authorities in the field of UCDs and practicing pediatricians in training. Although the evidence degree did hardly ever exceed level C (evidence from non-analytical studies like case reports and series), it was sufficient to guide practice on both acute and chronic presentations, address diagnosis, management, monitoring, outcomes, and psychosocial and ethical issues. Also, it identified knowledge voids that must be filled by future research. We believe these guidelines will help to: harmonise practice, set common standards and spread good practices with a positive impact on the outcomes of UCD patients. ; Development of these guidelines was financially supported by the "Guideline-Pool" from the German Metabolic Society (Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen) who received funding from Cytonet, Merck Darmstadt, Merck Serono, Orphan Europe, SHS International. The second guideline group meeting was in addition supported by Nutricia Italia, Orphan Europe and Swedish Orphan International. The third GDG meeting received additional financial and logistic support from CIBERER, Spain. The authors confirm full independence from the aforementioned sponsors who did not influence the guidelines development at any stage. JH receives support for the scientific work on UCDs from the Swiss National Science Foundation (grant 310030_127184/1). VR received support from grants BFU2008-05021 of the Spanish Ministry of Science and Prometeo/2009/051 of the Valencian Government. CDV was supported by the grant "CCM 2010: Costruzione di percorsi diagnostico-assistenziali per le malattie oggetto di screening neonatale allargato" from the Italian Ministry of Health. The clinical fellowship of DM is supported by the "Associazione la Vita è un Dono". Distribution of the guidelines is endorsed by the DGKJ (Deutsche Gesellschaft für Kinder- und Jugendmedizin) which offers support for translations. These guidelines have been adopted by and will be further developed under the umbrella of the "E-IMD" project which has received funding from the European Union, in the framework of the Health Programme. ; Peer Reviewed
Background: MetabERN is one of the 24 European Reference Networks created according to the European Union directive 2011/24/EU on patient's rights in cross border healthcare. MetabERN associates 69 centres in 18 countries, which provide care for patients with Hereditary Metabolic Diseases, and have the mission to reinforce research and provide training for health professionals in this field. MetabERN performed a survey in December 2017 with the aim to produce an overview documenting research activities and potentials within the network. As the centres are multidisciplinary, separated questionnaires were sent to the clinical, university and laboratory teams. Answers were received from 52 out of the 69 centres of the network, covering 16 countries. A descriptive analysis of the information collected is presented. Results: The answers indicate a marked interest of the respondents for research, who expressed high motivation and commitment, and estimated that the conditions to do research in their institution were mostly satisfactory. They are active in research, which according to several indicators, is competitive and satisfies standards of excellence, as well as the education programs offered in the respondent's universities. Research in the centres is primarily performed in genetics, pathophysiology, and epidemiology, and focuses on issues related to diagnosis. Few respondents declared having activity in human and social sciences, including research on patient's quality of life, patient's awareness, or methods for social support. Infrastructures offering services for medical research were rarely known and used by respondents, including national and international biobanking platforms. In contrast, respondents often participate to patient registries, even beyond their specific field of interest. Conclusions: Taken as a whole, these results provide an encouraging picture of the research capacities and activities in the MetabERN network, which, with respect to the number and representativeness of the investigated centres, gives a comprehensive picture of research on Hereditary Metabolic Diseases in Europe, as well as the priorities for future actions. Marginal activity in human and social sciences points out the limited multidisciplinary constitution of the responding teams with possible consequences on their current capability to participate to patient's empowerment programs and efficiently collaborate with patient's advocacy groups.
In: Heard , J-M , Bellettato , C , van Lingen , C , Scarpa , M , Debray , F-G , Nassogne , M-C C , van Coster , R , de Meirleir , L , Eyskens , F , Morava , E , Baric , I , Kozich , V , Lund , A M , Germain , D , Belmatoug , N , Guffon , N , Labrune , P , Gouya , L , de Lonlay , P , Schiff , M , Dobbelaere , D , Chabrol , B , Das , A M , Spiekerkoetter , U , Rutsch , F , Ploeckinger , U , Mohnike , K , Hahn , A , Kölker , S , Ullrich , K , Balogh , I , Bembi , B , Donati , M A , Gasperini , S , Parenti , G , Salviati , A , Vici , C-D , di Rocco , M , Cefalo , G , Burlina , A , Ceccarini , G , Federico , A , van der Ploeg , A , Rubio-Gozalbo , M-E , van Spronsen , F , Visser , G , Bosch , A , Tangeraas , T , Sanderberg , S , Kieć-Wilk , B , Gaspar , A-M S M , Martins , E , Silva , E-M F R , de Abreu Freire Diogo Matos , L-M , Azevedo , O , Tansek , M-Z , Couce-Pico , M-L , Cazorla , A G , Azuara , L A-E , del Toro-Riera , M , Lajic , S , Darin , N , Deegan , P , Vijaym , S , Chronopoulou , E , Jones , S , Chakrapani , A & Hiwot , T 2019 , ' Research activity and capability in the European reference network MetabERN ' , Orphanet Journal of Rare Diseases , vol. 14 , no. 1 , 119 . https://doi.org/10.1186/s13023-019-1091-8
Background: MetabERN is one of the 24 European Reference Networks created according to the European Union directive 2011/24/EU on patient's rights in cross border healthcare. MetabERN associates 69 centres in 18 countries, which provide care for patients with Hereditary Metabolic Diseases, and have the mission to reinforce research and provide training for health professionals in this field. MetabERN performed a survey in December 2017 with the aim to produce an overview documenting research activities and potentials within the network. As the centres are multidisciplinary, separated questionnaires were sent to the clinical, university and laboratory teams. Answers were received from 52 out of the 69 centres of the network, covering 16 countries. A descriptive analysis of the information collected is presented. Results: The answers indicate a marked interest of the respondents for research, who expressed high motivation and commitment, and estimated that the conditions to do research in their institution were mostly satisfactory. They are active in research, which according to several indicators, is competitive and satisfies standards of excellence, as well as the education programs offered in the respondent's universities. Research in the centres is primarily performed in genetics, pathophysiology, and epidemiology, and focuses on issues related to diagnosis. Few respondents declared having activity in human and social sciences, including research on patient's quality of life, patient's awareness, or methods for social support. Infrastructures offering services for medical research were rarely known and used by respondents, including national and international biobanking platforms. In contrast, respondents often participate to patient registries, even beyond their specific field of interest. Conclusions: Taken as a whole, these results provide an encouraging picture of the research capacities and activities in the MetabERN network, which, with respect to the number and representativeness of the investigated centres, gives a comprehensive picture of research on Hereditary Metabolic Diseases in Europe, as well as the priorities for future actions. Marginal activity in human and social sciences points out the limited multidisciplinary constitution of the responding teams with possible consequences on their current capability to participate to patient's empowerment programs and efficiently collaborate with patient's advocacy groups.