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.
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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.
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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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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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