Capturing phenotypic heterogeneity in MPS I: Results of an international consensus procedure

Minke H. de Ru, Quirine G A Teunissen, Johanna H. van der Lee, Michael Beck, Olaf A. Bodamer, Lorne A. Clarke, Carla E. Hollak, Shuan Pei Lin, Maria Veronica Munoz Rojas, Gregory M. Pastores, Julian A. Raiman, Maurizio Scarpa, Eileen P. Treacy, Anna Tylki-Szymanska, Edmond Wraith, Jiri Zeman, Frits A. Wijburg

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Mucopolysaccharidosis type I (MPS I) is traditionally divided into three phenotypes: the severe Hurler (MPS I-H) phenotype, the intermediate Hurler-Scheie (MPS I-H/S) phenotype and the attenuated Scheie (MPS I-S) phenotype. However, there are no clear criteria for delineating the different phenotypes. Because decisions about optimal treatment (enzyme replacement therapy or hematopoietic stem cell transplantation) need to be made quickly and depend on the presumed phenotype, an assessment of phenotypic severity should be performed soon after diagnosis. Therefore, a numerical severity scale for classifying different MPS I phenotypes at diagnosis based on clinical signs and symptoms was developed. Methods: A consensus procedure based on a combined modified Delphi method and a nominal group technique was undertaken. It consisted of two written rounds and a face-to-face meeting. Sixteen MPS I experts participated in the process. The main goal was to identify the most important indicators of phenotypic severity and include these in a numerical severity scale. The correlation between the median subjective expert MPS I rating and the scores derived from this severity scale was used as an indicator of validity. Results: Full consensus was reached on six key clinical items for assessing severity: age of onset of signs and symptoms, developmental delay, joint stiffness/arthropathy/contractures, kyphosis, cardiomyopathy and large head/frontal bossing. Due to the remarkably large variability in the expert MPS I assessments, however, a reliable numerical scale could not be constructed. Because of this variability, such a scale would always result in patients whose calculated severity score differed unacceptably from the median expert severity score, which was considered to be the 'gold standard'. Conclusions: Although consensus was reached on the six key items for assessing phenotypic severity in MPS I, expert opinion on phenotypic severity at diagnosis proved to be highly variable. This subjectivity emphasizes the need for validated biomarkers and improved genotype-phenotype correlations that can be incorporated into phenotypic severity assessments at diagnosis.

Original languageEnglish
JournalOrphanet Journal of Rare Diseases
DOIs
StateAccepted/In press - Apr 23 2012

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Mucopolysaccharidosis I
Phenotype
Signs and Symptoms
Enzyme Replacement Therapy
Kyphosis
Joint Diseases
Hematopoietic Stem Cell Transplantation
Expert Testimony
Genetic Association Studies
Contracture
Cardiomyopathies
Age of Onset

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Genetics(clinical)
  • Medicine(all)

Cite this

de Ru, M. H., Teunissen, Q. G. A., van der Lee, J. H., Beck, M., Bodamer, O. A., Clarke, L. A., ... Wijburg, F. A. (Accepted/In press). Capturing phenotypic heterogeneity in MPS I: Results of an international consensus procedure. Orphanet Journal of Rare Diseases. https://doi.org/10.1186/1750-1172-7-22

Capturing phenotypic heterogeneity in MPS I : Results of an international consensus procedure. / de Ru, Minke H.; Teunissen, Quirine G A; van der Lee, Johanna H.; Beck, Michael; Bodamer, Olaf A.; Clarke, Lorne A.; Hollak, Carla E.; Lin, Shuan Pei; Munoz Rojas, Maria Veronica; Pastores, Gregory M.; Raiman, Julian A.; Scarpa, Maurizio; Treacy, Eileen P.; Tylki-Szymanska, Anna; Wraith, Edmond; Zeman, Jiri; Wijburg, Frits A.

In: Orphanet Journal of Rare Diseases, 23.04.2012.

Research output: Contribution to journalArticle

de Ru, MH, Teunissen, QGA, van der Lee, JH, Beck, M, Bodamer, OA, Clarke, LA, Hollak, CE, Lin, SP, Munoz Rojas, MV, Pastores, GM, Raiman, JA, Scarpa, M, Treacy, EP, Tylki-Szymanska, A, Wraith, E, Zeman, J & Wijburg, FA 2012, 'Capturing phenotypic heterogeneity in MPS I: Results of an international consensus procedure', Orphanet Journal of Rare Diseases. https://doi.org/10.1186/1750-1172-7-22
de Ru, Minke H. ; Teunissen, Quirine G A ; van der Lee, Johanna H. ; Beck, Michael ; Bodamer, Olaf A. ; Clarke, Lorne A. ; Hollak, Carla E. ; Lin, Shuan Pei ; Munoz Rojas, Maria Veronica ; Pastores, Gregory M. ; Raiman, Julian A. ; Scarpa, Maurizio ; Treacy, Eileen P. ; Tylki-Szymanska, Anna ; Wraith, Edmond ; Zeman, Jiri ; Wijburg, Frits A. / Capturing phenotypic heterogeneity in MPS I : Results of an international consensus procedure. In: Orphanet Journal of Rare Diseases. 2012.
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abstract = "Background: Mucopolysaccharidosis type I (MPS I) is traditionally divided into three phenotypes: the severe Hurler (MPS I-H) phenotype, the intermediate Hurler-Scheie (MPS I-H/S) phenotype and the attenuated Scheie (MPS I-S) phenotype. However, there are no clear criteria for delineating the different phenotypes. Because decisions about optimal treatment (enzyme replacement therapy or hematopoietic stem cell transplantation) need to be made quickly and depend on the presumed phenotype, an assessment of phenotypic severity should be performed soon after diagnosis. Therefore, a numerical severity scale for classifying different MPS I phenotypes at diagnosis based on clinical signs and symptoms was developed. Methods: A consensus procedure based on a combined modified Delphi method and a nominal group technique was undertaken. It consisted of two written rounds and a face-to-face meeting. Sixteen MPS I experts participated in the process. The main goal was to identify the most important indicators of phenotypic severity and include these in a numerical severity scale. The correlation between the median subjective expert MPS I rating and the scores derived from this severity scale was used as an indicator of validity. Results: Full consensus was reached on six key clinical items for assessing severity: age of onset of signs and symptoms, developmental delay, joint stiffness/arthropathy/contractures, kyphosis, cardiomyopathy and large head/frontal bossing. Due to the remarkably large variability in the expert MPS I assessments, however, a reliable numerical scale could not be constructed. Because of this variability, such a scale would always result in patients whose calculated severity score differed unacceptably from the median expert severity score, which was considered to be the 'gold standard'. Conclusions: Although consensus was reached on the six key items for assessing phenotypic severity in MPS I, expert opinion on phenotypic severity at diagnosis proved to be highly variable. This subjectivity emphasizes the need for validated biomarkers and improved genotype-phenotype correlations that can be incorporated into phenotypic severity assessments at diagnosis.",
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AU - de Ru, Minke H.

AU - Teunissen, Quirine G A

AU - van der Lee, Johanna H.

AU - Beck, Michael

AU - Bodamer, Olaf A.

AU - Clarke, Lorne A.

AU - Hollak, Carla E.

AU - Lin, Shuan Pei

AU - Munoz Rojas, Maria Veronica

AU - Pastores, Gregory M.

AU - Raiman, Julian A.

AU - Scarpa, Maurizio

AU - Treacy, Eileen P.

AU - Tylki-Szymanska, Anna

AU - Wraith, Edmond

AU - Zeman, Jiri

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N2 - Background: Mucopolysaccharidosis type I (MPS I) is traditionally divided into three phenotypes: the severe Hurler (MPS I-H) phenotype, the intermediate Hurler-Scheie (MPS I-H/S) phenotype and the attenuated Scheie (MPS I-S) phenotype. However, there are no clear criteria for delineating the different phenotypes. Because decisions about optimal treatment (enzyme replacement therapy or hematopoietic stem cell transplantation) need to be made quickly and depend on the presumed phenotype, an assessment of phenotypic severity should be performed soon after diagnosis. Therefore, a numerical severity scale for classifying different MPS I phenotypes at diagnosis based on clinical signs and symptoms was developed. Methods: A consensus procedure based on a combined modified Delphi method and a nominal group technique was undertaken. It consisted of two written rounds and a face-to-face meeting. Sixteen MPS I experts participated in the process. The main goal was to identify the most important indicators of phenotypic severity and include these in a numerical severity scale. The correlation between the median subjective expert MPS I rating and the scores derived from this severity scale was used as an indicator of validity. Results: Full consensus was reached on six key clinical items for assessing severity: age of onset of signs and symptoms, developmental delay, joint stiffness/arthropathy/contractures, kyphosis, cardiomyopathy and large head/frontal bossing. Due to the remarkably large variability in the expert MPS I assessments, however, a reliable numerical scale could not be constructed. Because of this variability, such a scale would always result in patients whose calculated severity score differed unacceptably from the median expert severity score, which was considered to be the 'gold standard'. Conclusions: Although consensus was reached on the six key items for assessing phenotypic severity in MPS I, expert opinion on phenotypic severity at diagnosis proved to be highly variable. This subjectivity emphasizes the need for validated biomarkers and improved genotype-phenotype correlations that can be incorporated into phenotypic severity assessments at diagnosis.

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