title: Clinical course of sly syndrome (mucopolysaccharidosis type VII).
abstract: Mucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of β-glucuronidase (GUS). Patients' phenotypes vary from severe forms with hydrops fetalis, skeletal dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data.
  
  
  
  We have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease.
  
  
  
  We collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS.
  
  
  
  MPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity of the clinical course, if the patient survives infancy.
authors.affiliation: Department of Pediatrics, School of Medicine, Saint Louis University, St. Louis, Missouri, USA Edward A. Doisy Department of Biochemistry and Molecular Biology, School of Medicine, Saint Louis University, St. Louis, Missouri, USA.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Montaño
authors.affiliation: Metabolic and Clinical Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia.
authors.forename: Ngu
authors.initials: N
authors.lastname: Lock-Hock
authors.affiliation: Oregon Health & Science University, Portland, Oregon, USA Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA Current Affiliation: University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Steiner
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Brett H
authors.initials: BH
authors.lastname: Graham
authors.affiliation: Consultorio de Enfermedades Metabólicas, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina.
authors.forename: Marina
authors.initials: M
authors.lastname: Szlago
authors.affiliation: University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Greenstein
authors.affiliation: Fundació, Hospital Sant Joan De Déu, Centre for Biomedical Research on Rare Diseases, Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Pineda
authors.affiliation: Hospital Universitario Virgen del Rocío and Universidad de Sevilla, Sevilla, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez-Meneses
authors.affiliation: Faculty of Medicine, Ege University, Izmir, Turkey.
authors.forename: Mahmut
authors.initials: M
authors.lastname: Çoker
authors.affiliation: Division of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Bartholomew
authors.affiliation: Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sands
authors.affiliation: Division of Metabolic Disorders, CHOC, Children's Hospital Orange County, Orange, California, USA Department of Pediatrics, University of California-Irvine School of Medicine, Orange, California, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Wang
authors.affiliation: Medical Genetics Service/HCPA & Department of Genetics/UFRGS, Porto Alegre, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Macaya
authors.affiliation: New York University Medical Center, New York, New York, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Pastores
authors.affiliation: University of Michigan Health Systems, Ann Arbor, Michigan, USA Minnesota Neonatal Physicians P.A., Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Anastasia K
authors.initials: AK
authors.lastname: Ketko
authors.affiliation: Gazi University Faculty of Medicine, Ankara, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Ezgü
authors.affiliation: Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Childrens Hospital, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Laila
authors.initials: L
authors.lastname: Arash
authors.affiliation: Childrens Hospital, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Beck
authors.affiliation: Genetics Institute, Cedars Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Rena E
authors.initials: RE
authors.lastname: Falk
authors.affiliation: Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Kaustuv
authors.initials: K
authors.lastname: Bhattacharya
authors.affiliation: Hospital Infantil Sabará, Sao Paulo and Sao Paulo University, Sao Paulo, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Franco
authors.affiliation: Seattle children's Hospital, Seattle, Washington, USA.
authors.forename: Klane K
authors.initials: KK
authors.lastname: White
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Mitchell
authors.affiliation: Department of Human and Medical Genetics, Vilnius University, Vilnius, Lithuania.
authors.forename: Loreta
authors.initials: L
authors.lastname: Cimbalistiene
authors.affiliation: School of Medicine, Saint Louis University, St. Louis, Missouri, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Holtz
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, School of Medicine, Saint Louis University, St. Louis, Missouri, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Sly
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007223:Infant; D016464:Lysosomal Storage Diseases / Q000378:metabolism / Q000473:pathology; D008297:Male; D016538:Mucopolysaccharidosis VII / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D005966:Glucuronidase
keywords: Clinical genetics; Genetics; Metabolic disorders