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Genotype-phenotype correlations
Original article
Clinical course of sly syndrome (mucopolysaccharidosis type VII)
  1. Adriana M Montaño1,2,
  2. Ngu Lock-Hock3,
  3. Robert D Steiner4,5,6,
  4. Brett H Graham7,
  5. Marina Szlago8,
  6. Robert Greenstein9,
  7. Mercedes Pineda10,
  8. Antonio Gonzalez-Meneses11,
  9. Mahmut Çoker12,
  10. Dennis Bartholomew13,
  11. Mark S Sands14,
  12. Raymond Wang15,16,
  13. Roberto Giugliani17,
  14. Alfons Macaya18,
  15. Gregory Pastores19,
  16. Anastasia K Ketko20,21,
  17. Fatih Ezgü22,
  18. Akemi Tanaka23,
  19. Laila Arash24,
  20. Michael Beck24,
  21. Rena E Falk25,
  22. Kaustuv Bhattacharya26,
  23. José Franco27,
  24. Klane K White28,
  25. Grant A Mitchell29,
  26. Loreta Cimbalistiene30,
  27. Max Holtz31,
  28. William S Sly2
  1. 1Department of Pediatrics, School of Medicine, Saint Louis University, St. Louis, Missouri, USA
  2. 2Edward A. Doisy Department of Biochemistry and Molecular Biology, School of Medicine, Saint Louis University, St. Louis, Missouri, USA
  3. 3Metabolic and Clinical Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
  4. 4Oregon Health & Science University, Portland, Oregon, USA
  5. 5Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA
  6. 6Current Affiliation: University of Wisconsin, Madison, Wisconsin, USA
  7. 7Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  8. 8Consultorio de Enfermedades Metabólicas, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina
  9. 9University of Connecticut Health Center, Farmington, Connecticut, USA
  10. 10Fundació, Hospital Sant Joan De Déu, Centre for Biomedical Research on Rare Diseases, Instituto de Salud Carlos III, Barcelona, Spain
  11. 11Hospital Universitario Virgen del Rocío and Universidad de Sevilla, Sevilla, Spain
  12. 12Faculty of Medicine, Ege University, Izmir, Turkey
  13. 13Division of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, Ohio, USA
  14. 14Washington University School of Medicine, St Louis, Missouri, USA
  15. 15Division of Metabolic Disorders, CHOC, Children's Hospital Orange County, Orange, California, USA
  16. 16Department of Pediatrics, University of California-Irvine School of Medicine, Orange, California, USA
  17. 17Medical Genetics Service/HCPA & Department of Genetics/UFRGS, Porto Alegre, Brazil
  18. 18Hospital Universitari Vall d'Hebron, Barcelona, Spain
  19. 19New York University Medical Center, New York, New York, USA
  20. 20University of Michigan Health Systems, Ann Arbor, Michigan, USA
  21. 21Minnesota Neonatal Physicians P.A., Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA
  22. 22Gazi University Faculty of Medicine, Ankara, Turkey
  23. 23Osaka City University Graduate School of Medicine, Osaka, Japan
  24. 24Childrens Hospital, Johannes Gutenberg University Medical Center, Mainz, Germany
  25. 25Genetics Institute, Cedars Sinai Medical Center, Los Angeles, California, USA
  26. 26Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead, Sydney, Australia
  27. 27Hospital Infantil Sabará, Sao Paulo and Sao Paulo University, Sao Paulo, Brazil
  28. 28Seattle children's Hospital, Seattle, Washington, USA
  29. 29Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada
  30. 30Department of Human and Medical Genetics, Vilnius University, Vilnius, Lithuania
  31. 31School of Medicine, Saint Louis University, St. Louis, Missouri, USA
  1. Correspondence to Dr Adriana M Montaño, Doisy Research Center, Department of Pediatrics, Saint Louis University, 1100 South Grand Blvd., Room 311, St. Louis, MO 63104, USA; montana{at}slu.edu

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.

  • Clinical genetics
  • Genetics
  • Metabolic disorders

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/jmedgenet-2015-103322

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