title: A systematic review of the prevalence of Morquio A syndrome: challenges for study reporting in rare diseases.
abstract: BACKGROUND
  Morquio A (MPS IVA) is a rare disease characterised by a deficiency of N-acetylgalactosamine-6 sulfatase (GALNS) and presenting with short stature, abnormal gait, cervical spine instability and shortened lifespan.
  
  
  OBJECTIVE
  To prepare a systematic review of the prevalence of Morquio A in multiple countries and suggest recommendations for reporting rare diseases.
  
  
  METHODS
  Medline, Medline In-Process, Medline Daily Update, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database and PROSPERO were searched from inception to October 2013 to identify relevant information on the epidemiology of Morquio A. Forty Patient Organisation Representatives (POR) and Key Opinion Leaders (KOL) across 24 countries were contacted for data. Observational studies were included and case reports were excluded. Searches were performed without date or language restriction. Two researchers independently screened and extracted data. Quality of study reporting was assessed using a checklist adapted from STROBE (STrengthening the Reporting of OBservational studies in Epidemiology). Point or birth prevalence was stratified according to diagnostic method and discussed narratively.
  
  
  RESULTS
  In total 9,074 records were retrieved from searching and 25 studies were included for data extraction. Twenty out of 40 KOL and POR responded (50%) and 9 provided data (23%). Point prevalence of Morquio A was 1 per 926,000 in Australia, 1 per 1,872,000 in Malaysia and 1 per 599,000 in UK and Morquio (unclassified) was 1 per 323, 000 in Denmark. Birth prevalence of Morquio A (using recommended diagnostic methods) ranged from 1 per 71,000 in UAE to 1 per 500,000 in Japan. All results were compromised by poor study reporting and internal validity.
  
  
  CONCLUSIONS
  The review highlighted that there is a misunderstanding of the definitions for prevalence and incidence in the field; that studies were poorly reported (diagnostic methods and patient characteristics) and that no suitable quality assessment tool exists. Overestimation and underestimation of prevalence data can occur. Bespoke reporting guidelines and a quality assessment tool specifically for prevalence of rare diseases are recommended.
authors.affiliation: Kleijnen Systematic Reviews, Unit 6, Escrick Business Park, Escrick, York, YO19 6FD, UK. Regina@systematic-reviews.com.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Leadley
authors.affiliation: Kleijnen Systematic Reviews, Unit 6, Escrick Business Park, Escrick, York, YO19 6FD, UK. Shona@systematic-reviews.com.
authors.forename: Shona
authors.initials: S
authors.lastname: Lang
authors.affiliation: Kleijnen Systematic Reviews, Unit 6, Escrick Business Park, Escrick, York, YO19 6FD, UK. Kate@systematic-reviews.com.
authors.forename: Kate
authors.initials: K
authors.lastname: Misso
authors.affiliation: BeSyReBekkering Systematic Reviews, Geel, Belgium. Trudy.Bekkering@med.kuleuven.be.
authors.forename: Trudy
authors.initials: T
authors.lastname: Bekkering
authors.affiliation: Kleijnen Systematic Reviews, Unit 6, Escrick Business Park, Escrick, York, YO19 6FD, UK. Janine@systematic-reviews.com.
authors.forename: Janine
authors.initials: J
authors.lastname: Ross
authors.affiliation: Japan society of patients and families with Mucopolysaccharidoses, 2-37-3, Minamisyojyaku, Suita-Shi, Osaka, 564-0012, Japan. mps_office@mps-japan.org.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Department of Biochemical Genetics, SA Pathology (at WCH), 72 King William Road, North Adelaide, SA, 5006, Australia. michael.fietz@health.sa.gov.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Fietz
authors.affiliation: Chief of the Medical Genetics Service, Clinic Hospital of Porto, Porto Alegre, Rio Grande do Sul, Brazil. rgiugliani@hcpa.ufrgs.br.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Clinical lead- Adult Inherited Metabolic Disorders, Consultant Transitional Metabolic Medicine, Manchester Academic Health Science Centre, The Mark Holland Metabolic Unit, Salford Royal Foundation NHS Trust, Ladywell NW2- 2nd Floor Room 107, Salford, Manchester, M6 8H, UK. Chris.Hendriksz@srft.nhs.uk.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hendriksz
authors.affiliation: Consultant Pediatrician and Clinical Geneticist, Clinical Genetics & Metabolic Department, Kuala Lumpur Hospital, Jalan Pahang, Kuala Lumpur, 50586, Malaysia. ngulh@hotmail.com.
authors.forename: Ngu Lock
authors.initials: NL
authors.lastname: Hock
authors.affiliation: Metabolic physician and Clinical geneticist Department of Metabolic Medicine, Royal Children's Hospital, Brisbane, Australia. jim.mcgill@health.qld.gov.au.
authors.forename: Jim
authors.initials: J
authors.lastname: McGill
authors.affiliation: Snr Market Access Manager EUMEA, BioMarin Europe Ltd, 164 Shaftesbury Ave, London, WC2H 8HL, United Kingdom. AOlaye@bmrn.com.
authors.forename: Andrew
authors.initials: A
authors.lastname: Olaye
authors.affiliation: Market Access & Public Policy EUMEA BioMarin Europe Ltd, 164 Shaftesbury Ave, London, WC2H 8HL, United Kingdom. MJain@bmrn.com.
authors.forename: Mohit
authors.initials: M
authors.lastname: Jain
authors.affiliation: Kleijnen Systematic Reviews, Unit 6, Escrick Business Park, Escrick, York, YO19 6FD, UK. Jos@systematic-reviews.com.|School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, Netherlands. Jos@systematic-reviews.com.
authors.forename: Jos
authors.initials: J
authors.lastname: Kleijnen
mesh_terms: D006801:Humans; D009085:Mucopolysaccharidosis IV / Q000453:epidemiology*; D015995:Prevalence; D035583:Rare Diseases