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Clinical course of sly syndrome (mucopolysaccharidosis type VII)

Montaño AM 1 , Lock-Hock N 2 , Steiner RD 3 , Graham BH 4 , Szlago M 5 , Greenstein R 6 Show all authors , Pineda M 7 , Gonzalez-Meneses A 8 , Çoker M 9 , Bartholomew D 10 , Sands MS 11 , Wang R 12 , Giugliani R 13 , Macaya A 14 , Pastores G 15 , Ketko AK 16 , Ezgü F 17 , Tanaka A 18 , Arash L 19 , Beck M 19 , Falk RE 20 , Bhattacharya K 21 , Franco J 22 , White KK 23 , Mitchell GA 24 , Cimbalistiene L 25 , Holtz M 26 , Sly WS 27

Affiliations 

  • 1 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
  • 2 Metabolic and Clinical Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
  • 3 Oregon Health & Science University, Portland, Oregon, USA Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA Current Affiliation: University of Wisconsin, Madison, Wisconsin, USA
  • 4 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  • 5 Consultorio de Enfermedades Metabólicas, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina
  • 6 University of Connecticut Health Center, Farmington, Connecticut, USA
  • 7 Fundació, Hospital Sant Joan De Déu, Centre for Biomedical Research on Rare Diseases, Instituto de Salud Carlos III, Barcelona, Spain
  • 8 Hospital Universitario Virgen del Rocío and Universidad de Sevilla, Sevilla, Spain
  • 9 Faculty of Medicine, Ege University, Izmir, Turkey
  • 10 Division of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, Ohio, USA
  • 11 Washington University School of Medicine, St Louis, Missouri, USA
  • 12 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
  • 13 Medical Genetics Service/HCPA & Department of Genetics/UFRGS, Porto Alegre, Brazil
  • 14 Hospital Universitari Vall d'Hebron, Barcelona, Spain
  • 15 New York University Medical Center, New York, New York, USA
  • 16 University of Michigan Health Systems, Ann Arbor, Michigan, USA Minnesota Neonatal Physicians P.A., Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA
  • 17 Gazi University Faculty of Medicine, Ankara, Turkey
  • 18 Osaka City University Graduate School of Medicine, Osaka, Japan
  • 19 Childrens Hospital, Johannes Gutenberg University Medical Center, Mainz, Germany
  • 20 Genetics Institute, Cedars Sinai Medical Center, Los Angeles, California, USA
  • 21 Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead, Sydney, Australia
  • 22 Hospital Infantil Sabará, Sao Paulo and Sao Paulo University, Sao Paulo, Brazil
  • 23 Seattle children's Hospital, Seattle, Washington, USA
  • 24 Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada
  • 25 Department of Human and Medical Genetics, Vilnius University, Vilnius, Lithuania
  • 26 School of Medicine, Saint Louis University, St. Louis, Missouri, USA
  • 27 Edward A. Doisy Department of Biochemistry and Molecular Biology, School of Medicine, Saint Louis University, St. Louis, Missouri, USA
J Med Genet, 2016 06;53(6):403-18.
PMID: 26908836 DOI: 10.1136/jmedgenet-2015-103322

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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