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Monitoring of Therapy for Mucopolysaccharidosis Type I Using Dysmorphometric Facial Phenotypic Signatures

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JIMD Reports, Volume 22

Part of the book series: JIMD Reports ((JIMD,volume 22))

Abstract

There is a pattern of progressive facial dysmorphology in mucopolysaccharidosis type I (MPS I). Advances in 3D facial imaging have facilitated the development of tools, including dysmorphometrics, to objectively and precisely detect these facial phenotypes. Therefore, we investigated the application of dysmorphometrics as a noninvasive therapy-monitoring tool, by longitudinally scoring facial dysmorphology in a child with MPS I receiving enzyme replacement therapy (ERT) and bone marrow transplantation (BMT). Both dysmorphometric measures showed a decreasing trend, and the greatest differences were found in the severity of facial discordance (Z-RMSE), displaying scores >3 SD higher than the mean at their peak, in comparison to Z-RSD scores that mostly fell within the normative range (maximum; 1.5 SD from the mean). In addition to the general trend of reduced facial dysmorphology with treatment, initial fluctuations were also evident that may have related to transient subcutaneous facial fluctuations, in the context of conditioning for bone marrow transplant. These findings support the potential of our approach as a sensitive, noninvasive, and rapid means of assessing treatment response or failure in clinical trials, and for established therapies, and would be applicable for other inherited disorders of metabolism.

Competing interests: None declared

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Abbreviations

3D:

Three dimensional

AM:

Anthropometric mask

BMT:

Bone marrow transplant

ERT:

Enzyme replacement therapy

GvHD:

Graft-versus-host disease

HSCT:

Hematopoietic stem cell transplantation

LSD:

Lysosomal storage disorder

MPS IH:

Mucopolysaccharidosis type I – Hurler syndrome

NE:

Normal equivalent

PCA:

Principal component analysis

PCs:

Principal components

RMSE:

Root mean squared error

RSD:

Relative significant discordance

SD:

Standard deviation

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Acknowledgments

We are indebted to the child with MPS I and his family for participation in this study and permission for image use. We would like to thank Genzyme Australia for providing an unrestricted educational grant. The Princess Margaret Hospital Foundation in Perth, Western Australia, also provided support for this study. RD-Connect, the associated National Health and Medical Research Council of Australia, and the Raine Clinician Research Fellowship supported GB’s contribution.

Author information

Authors and Affiliations

  1. School of Paediatrics and Child Health, University of Western Australia, D184, Perth, WA, 6840, Australia

    Stefanie Kung, Peter LeSouef, Jack Goldblatt, Andrew Martin & Gareth Baynam

  2. Cranio-maxillo-facial Unit, Princess Margaret Hospital for Children, Perth, WA, Australia

    Mark Walters

  3. Department of Electrical Engineering, ESAT/PSA, KU Leuven, Medical Image Computing, Leuven, Belgium

    Peter Claes

  4. UZ Leuven, Medical Imaging Research Center, Leuven, Belgium

    Peter Claes

  5. Medical IT Department, iMinds, KU Leuven, Leuven, Belgium

    Peter Claes

  6. Genetic Services of Western Australia, King Edward Memorial & Princess Margaret Hospitals, 4th Floor Agnes Walsh House, 374 Bagot Road, Subiaco, WA, 6008, Australia

    Jack Goldblatt & Gareth Baynam

  7. Western Australian Department of Health, Office of Population Health Genomics, Perth, WA, Australia

    Jack Goldblatt & Gareth Baynam

  8. Storage Disorders Clinic, Princess Margaret Hospital for Children, Perth, WA, Australia

    Shanti Balasubramaniam

  9. Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia

    Gareth Baynam

Authors
  1. Stefanie Kung
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  2. Mark Walters
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  3. Peter Claes
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  4. Peter LeSouef
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  5. Jack Goldblatt
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  6. Andrew Martin
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  7. Shanti Balasubramaniam
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  8. Gareth Baynam
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Corresponding authors

Correspondence to Stefanie Kung or Gareth Baynam .

Editor information

Editors and Affiliations

  1. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

  2. Division of Metabolism and Children’s Re, University Children’s Hospital Zurich, Zurich, Switzerland

    Matthias Baumgartner

  3. Tulane University Medical School, New Orleans, Louisiana, USA

    Eva Morava

  4. Division of Child and Adolescent Neurolo, Mayo Clinic, Rochester, Minnesota, USA

    Marc Patterson

  5. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, United Kingdom

    Shamima Rahman

  6. Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Frits Wijburg, MD, PhD

Appendices

Synopsis

Longitudinal quantification of objective and deeply precise changes in MPS I facial morphology during treatment demonstrates the potential of dysmorphometric 3D facial analysis as a noninvasive treatment response biomarker.

Compliance with Ethics Guidelines

Conflict of Interests

Stefanie Kung (SK), Mark Walters (MW), Peter Claes (PC), Peter LeSouef (PLS), Jack Goldblatt (JB), Andrew Martin (AM), Shanti Balasubramaniam (SB), and Gareth Baynam (GB) declare that they have no conflict of interests. Genzyme provided an unrestricted educational grant and had no role in the interpretation/analysis of the data or the decision to submit the manuscript for publication.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all participants included in the study.

Author Contributions

SK drafted the initial manuscript with subsequent revisions and input from MW, GB, JG, and PC. GB and JG conceived the study. SK acquired the longitudinal facial data and implemented the facial assessments. PC performed the facial mapping of the data and generated normative reference discordancy statistics. All authors were involved in the interpretation of the results. SB, AM, JG, and PLS provided valuable clinical insight into the patient’s treatment regime, and the investigated syndrome.

Guarantor

GB accepts full responsibility for this work and conduct of this study as guarantor for this article. He has had access to the research data and controls the decision to publish.

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© 2015 SSIEM and Springer-Verlag Berlin Heidelberg

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Kung, S. et al. (2015). Monitoring of Therapy for Mucopolysaccharidosis Type I Using Dysmorphometric Facial Phenotypic Signatures. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 22. JIMD Reports, vol 22. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_417

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  • DOI: https://doi.org/10.1007/8904_2015_417

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-47452-5

  • Online ISBN: 978-3-662-47453-2

  • eBook Packages: MedicineMedicine (R0)

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