title: Review and evaluation of the methodological quality of the existing guidelines and recommendations for inherited neurometabolic disorders.
abstract: BACKGROUND
  Inherited neurometabolic disorders (iNMDs) represent a group of almost seven hundred rare diseases whose common manifestations are clinical neurologic or cognitive symptoms that can appear at any time, in the first months/years of age or even later in adulthood. Early diagnosis and timely treatments are often pivotal for the favorable course of the disease. Thus, the elaboration of new evidence-based recommendations for iNMD diagnosis and management is increasingly requested by health care professionals and patients, even though the methodological quality of existing guidelines is largely unclear. InNerMeD-I-Network is the first European network on iNMDs that was created with the aim of sharing and increasing validated information about diagnosis and management of neurometabolic disorders. One of the goals of the project was to determine the number and the methodological quality of existing guidelines and recommendations for iNMDs.
  
  
  METHODS
  We performed a systematic search on PubMed, the National Guideline Clearinghouse (NGC), the Guidelines International Network (G-I-N), the Scottish Intercollegiate Guideline Network (SIGN) and the National Institute for Health and Care Excellence (NICE) to identify all the published guidelines and recommendations for iNMDs from January 2000 to June 2015. The methodological quality of the selected documents was determined using the AGREE II instrument, an appraisal tool composed of 6 domains covering 23 key items.
  
  
  RESULTS
  A total of 55 records met the inclusion criteria, 11 % were about groups of disorders, whereas the majority encompassed only one disorder. Lysosomal disorders, and in particular Fabry, Gaucher disease and mucopolysaccharidoses where the most studied. The overall methodological quality of the recommendation was acceptable and increased over time, with 25 % of the identified guidelines strongly recommended by the appraisers, 64 % recommended, and 11 % not recommended. However, heterogeneity in the obtained scores for each domain was observed among documents covering different groups of disorders and some domains like 'stakeholder involvement' and 'applicability' were generally scarcely addressed.
  
  
  CONCLUSIONS
  Greater efforts should be devoted to improve the methodological quality of guidelines and recommendations for iNMDs and AGREE II instrument seems advisable for new guideline development. The elaboration of new guidelines encompassing still uncovered disorders is badly needed.
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Linda
authors.initials: L
authors.lastname: Cassis
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Elisenda
authors.initials: E
authors.lastname: Cortès-Saladelafont
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Molero-Luis
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Delia
authors.initials: D
authors.lastname: Yubero
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Maria Julieta
authors.initials: MJ
authors.lastname: González
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Ormazábal
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Fons
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Jou
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sierra
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Castejon Ponce
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Ramos
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Judith
authors.initials: J
authors.lastname: Armstrong
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: M Mar
authors.initials: MM
authors.lastname: O'Callaghan
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Casado
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Montero
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Meavilla-Olivas
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Artuch
authors.affiliation: Department of Pediatrics, University Hospital Center Zagreb, Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Barić
authors.affiliation: Gianni Benzi Pharmacological Research Foundation, Valenzano, BA, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Bartoloni
authors.affiliation: Department of Women and Children Health, Brains for Brain Foundation, Padova, Italy.
authors.forename: Cinzia Maria
authors.initials: CM
authors.lastname: Bellettato
authors.affiliation: Gianni Benzi Pharmacological Research Foundation, Valenzano, BA, Italy.
authors.forename: Fedele
authors.initials: F
authors.lastname: Bonifazi
authors.affiliation: Gianni Benzi Pharmacological Research Foundation, Valenzano, BA, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ceci
authors.affiliation: Department of Pediatrics, University Hospital Center Zagreb, Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia.
authors.forename: Ljerka
authors.initials: L
authors.lastname: Cvitanović-Šojat
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christine I
authors.initials: CI
authors.lastname: Dali
authors.affiliation: Department of Women and Children Health, Brains for Brain Foundation, Padova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: D'Avanzo
authors.affiliation: Department of Pediatrics, University Hospital Center Zagreb, Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia.
authors.forename: Ksenija
authors.initials: K
authors.lastname: Fumic
authors.affiliation: Gianni Benzi Pharmacological Research Foundation, Valenzano, BA, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Giannuzzi
authors.affiliation: Department of Women and Children Health, Brains for Brain Foundation, Padova, Italy.|Department of Pediatric and Adolescent Medicine, Centre for Rare Diseases, Horst Schmidt Klinik Wiesbaden, Wiesbaden, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Lampe
authors.affiliation: Department of Women and Children Health, Brains for Brain Foundation, Padova, Italy.|Department of Pediatric and Adolescent Medicine, Centre for Rare Diseases, Horst Schmidt Klinik Wiesbaden, Wiesbaden, Germany.|Department of Women's and Children's Health, University of Padova, Padova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Scarpa
authors.affiliation: Neurology, gastroenterology pathology and clinical biochemistry Departments, IRP-HSJD and CIBERER, Barcelona, Spain. agarcia@hsjdbcn.org.
authors.forename: Ángels
authors.initials: Á
authors.lastname: Garcia-Cazorla
mesh_terms: D001928:Brain Diseases, Metabolic / Q000175:diagnosis* / Q000628:therapy*; D019317:Evidence-Based Medicine / Q000592:standards*; D006801:Humans; D017410:Practice Guidelines as Topic / Q000592:standards*