Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2012

Open Access 01-12-2012 | Research

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

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

Published in: Orphanet Journal of Rare Diseases | Issue 1/2012

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Neufeld EF, Muenzer J: The mucopolysaccharidoses. In The Online Metabolic and Molecular Bases of Inherited Disease chapter 136 edition. Edited by: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A. New York: McGraw-Hill; 2007.
2.
Terlato NJ, Cox GF: Can mucopolysaccharidosis type I disease severity be predicted based on a patient's genotype? A comprehensive review of the literature. Genet Med. 2003, 5: 286-294. 10.1097/01.GIM.0000078027.83236.49.CrossRefPubMed
3.
Bertola F, Filocamo M, Casati G, Mort M, Rosano C, Tylki-Szymanska A, Tüysüz B, Gabrielli O, Grossi S, Scarpa M, Parenti G, Antuzzi D, Dalmau J, Rocco MD, Vici CD, Okur I, Rosell J, Rovelli A, Furlan F, Rigoldi M, Biondi A, Cooper DN, Parini R: IDUA mutational profiling of a cohort of 102 European patients with Mucopolysaccharidosis type I: identification and characterization of 35 novel α-L-iduronidase (IDUA) alleles. Hum Mutat. 2011, 32: E2189-E2210. 10.1002/humu.21479.CrossRefPubMed
4.
Murphy AM, Lambert D, Treacy EP, O'Meara A, Lynch SA: Incidence and prevalence of mucopolysaccharidosis type 1 in the Irish republic. Arch Dis Child. 2009, 94: 52-54. 10.1136/adc.2007.135772.CrossRefPubMed
5.
Lin HY, Lin SP, Chuang CK, Niu DM, Chen MR, Tsai FJ, Chao MC, Chiu PC, Lin SJ, Tsai LP, Hwu WL, Lin JL: Incidence of the mucopolysaccharidoses in Taiwan, 1984-2004. Am J Med Genet A. 2009, 149A: 960-964. 10.1002/ajmg.a.32781.CrossRefPubMed
6.
Muenzer J, Wraith JE, Clarke LA: Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics. 2009, 123: 19-29. 10.1542/peds.2008-0416.CrossRefPubMed
7.
Pastores GM, Arn P, Beck M, Clarke JT, Guffon N, Kaplan P, Muenzer J, Norato DY, Shapiro E, Thomas J, Viskochil D, Wraith JE: The MPS I registry: design, methodology, and early findings of a global disease registry for monitoring patients with mucopolysaccharidosis type i. Mol Genet Metab. 2007, 91: 37-47. 10.1016/j.ymgme.2007.01.011.CrossRefPubMed
8.
Pastores GM, Meere PA: Musculoskeletal complications associated with lysosomal storage disorders: gaucher disease and Hurler-Scheie syndrome (mucopolysaccharidosis type I). Curr Opin Rheumatol. 2005, 17: 70-78. 10.1097/01.bor.0000147283.40529.13.CrossRefPubMed
9.
Vijay S, Wraith JE: Clinical presentation and follow-up of patients with the attenuated phenotype of mucopolysaccharidosis type I. Acta Paediatr. 2005, 94: 872-877. 10.1080/08035250510031584.CrossRefPubMed
10.
Boelens JJ, Prasad VK, Tolar J, Wynn RF, Peters C: Current international perspectives on hematopoietic stem cell transplantation for inherited metabolic disorders. Pediatr Clin North Am. 2010, 57: 123-145. 10.1016/j.pcl.2009.11.004.CrossRefPubMed
11.
Aldenhoven M, Boelens JJ, de Koning TJ: The clinical outcome of Hurler syndrome after stem cell transplantation. Biol Blood Marrow Transplant. 2008, 14: 485-498. 10.1016/j.bbmt.2008.01.009.CrossRefPubMed
12.
de Ru MH, Boelens JJ, Das AM, Jones SA, van der Lee JH, Mahlaoui N, Mengel E, Offringa M, O'Meara A, Parini R, Rovelli A, Sykora KW, Valayannopoulos V, Vellodi A, Wynn RF, Wijburg FA: Enzyme Replacement Therapy and/or Hematopoietic Stem Cell Transplantation at diagnosis in patients with Mucopolysaccharidosis type I: results of a European consensus procedure. Orphanet J Rare Dis. 2011, 10 (6): 55..CrossRef
13.
Kakkis ED, Muenzer J, Tiller GE, Waber L, Belmont J, Passage M, Izykowski B, Philips J, Doreshow R, Walot I, Hoft R, Neufeld EF: Enzyme replacement therapy in mucopolysaccharidosis I. N Engl J Med. 2001, 344: 182-188. 10.1056/NEJM200101183440304.CrossRefPubMed
14.
Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Swiedler SJ, Kakkis ED, Braakman T, Chadbourne E, Walton-Bowen K, Cox GF: Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alfa-l-iduronidase (laronidase). J Pediatr. 2004, 144: 581-588. 10.1016/j.jpeds.2004.01.046.CrossRefPubMed
15.
Sifuentes M, Doroshow R, Hoft R, Mason G, Walot I, Diament M, Okazaki S, Huff K, Cox GF, Swiedler SJ, Kakkis ED: A follow-op study of MPS I patients treated with laronidase enzyme replacement therapy for 6 years. Mol Genet Metab. 2007, 90: 171-180. 10.1016/j.ymgme.2006.08.007.CrossRefPubMed
16.
Wraith JE, Beck M, Lane R, van der Ploeg A, Shapiro E, Xue Y, Kakkis ED, Guffon N: Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alfa-l-iduronidase (laronidase). Paediatrics. 2007, 120: e37-e46. 10.1542/peds.2006-2156.CrossRef
17.
Clarke LA, Wraith JE, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Sidman M, Kakkis ED, Cox GF: Long-term efficacy and safety of laronidase in the treatment of Mucopolysaccharidosis I. Pediatrics. 2009, 123: 229-240. 10.1542/peds.2007-3847.CrossRefPubMed
18.
Kakkis ED, McEntee MF, Schmidtchen A, Neufeld EF, Ward DA, Gompf RE, Kania S, Bedolla C, Chien SL, Shull RM: Long-term and high-dose trials of enzyme replacement therapy in the canine model of mucopolysaccharidosis I. Biochem Mol Med. 1996, 58: 156-167. 10.1006/bmme.1996.0044.CrossRefPubMed
19.
Boelens JJ, Rocha V, Aldenhoven M, Wynn R, O'Meara A, Michel G, Ionescu I, Parikh S, Prasad VK, Szabolcs P, Escolar M, Gluckman E, Cavazzana-Calvo M, Kurtzberg J: EUROCORD, inborn error working party of ebmt and duke university: risk factor analysis of outcomes after unrelated cord blood transplantation in patients with hurler syndrome. Biol Blood Marrow Transplant. 2009, 15: 618-625. 10.1016/j.bbmt.2009.01.020.CrossRefPubMed
20.
Boelens JJ, Aldenhoven M, Purtill D, Eapen M, DeForr T, Wynn R, Cavazanna-Calvo M, Tolar J, Prasad VK, Escolar M, Gluckman E, Orchard P, Veys P, Kurtzberg J, Rocha V: Outcomes of transplantation using a various cell source in children with Hurlers syndrome after myelo-ablative conditioning. An Eurocord-EBMT-CIBMTR collaborative study. Biol Blood Marrow Transplant. 2010, 16 (Suppl 2): 180-181.CrossRef
21.
Gabrielli O, Clarke LA, Bruni S, Coppa GV: Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up. Pediatrics. 2010, 125: e183-e187. 10.1542/peds.2009-1728.CrossRefPubMed
22.
Jaeschke R, Guyatt GH, Dellinger P, Schünemann H, Levy MM, Kunz R, Norris S, Bion J: GRADE Working Group: Use of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive. BMJ. 2008, 337: a744-10.1136/bmj.a744.CrossRefPubMed
23.
Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B: Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol. 1997, 39: 214-223.CrossRefPubMed
24.
Streiner DL, Norman GR: Health measurement scales; a practical guide to their development and use. 2003, Oxford: Oxford University Press
25.
McGraw KO, Wong SP: Forming inferences about some intraclass correlation coefficients. Psychol Methods. 1996, 1: 30-46.CrossRef
26.
Blanchard S, Sadilek M, Scott CR, Turecek F, Gelb MH: Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: application to screening newborns for mucopolysaccharidosis I. Clin Chem. 2008, 54: 2067-2070. 10.1373/clinchem.2008.115410.PubMedCentralCrossRefPubMed
27.
Wang D, Eadala B, Sadilek M, Chamoles NA, Turecek F, Scott CR, Gelb MH: Tandem mass spectrometric analysis of dried blood spots for screening of mucopolysaccharidosis I in newborns. Clin Chem. 2005, 51: 898-900. 10.1373/clinchem.2004.047167.CrossRefPubMed
28.
Meikle PJ, Grasby DJ, Dean CJ, Lang DL, Bockmann M, Whittle AM, Fietz MJ, Simonsen H, Fuller M, Brooks DA, Hopwood JJ: Newborn screening for lysosomal storage disorders. Mol Genet Metab. 2006, 88: 307-314. 10.1016/j.ymgme.2006.02.013.CrossRefPubMed
29.
Randall DR, Colobong KE, Hemmelgarn H, Sinclair GB, Hetty E, Thomas A, Bodamer OA, Volkmar B, Fernhoff PM, Casey R, Chan AK, Mitchell G, Stockler S, Melancon S, Rupar T, Clarke LA: Heparin cofactor II-thrombin complex: a biomarker of MPS disease. Mol Genet Metab. 2008, 94: 456-461. 10.1016/j.ymgme.2008.05.001.CrossRefPubMed
30.
Langford-Smith KJ, Mercer J, Petty J, Tylee K, Church H, Roberts J, Moss G, Jones S, Wynn R, Wraith JE, Bigger BW: Heparin cofactor II-thrombin complex and dermatan sulphate:chondroitin sulphate ratio are biomarkers of short- and long-term treatment effects in mucopolysaccharide diseases. J Inherit Metab Dis. 2010, 34: 499-508.PubMedCentralCrossRefPubMed
Metadata
Title
Capturing phenotypic heterogeneity in MPS I: results of an international consensus procedure
Authors
Minke H de Ru
Quirine GA Teunissen
Johanna H van der Lee
Michael Beck
Olaf A Bodamer
Lorne A Clarke
Carla E Hollak
Shuan-Pei Lin
Maria-Verónica Muñoz Rojas
Gregory M Pastores
Julian A Raiman
Maurizio Scarpa
Eileen P Treacy
Anna Tylki-Szymanska
J Edmond Wraith
Jiri Zeman
Frits A Wijburg
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2012
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-7-22

Other articles of this Issue 1/2012

Orphanet Journal of Rare Diseases 1/2012 Go to the issue

Research

Early presentation of gait impairment in Wolfram Syndrome

Research

Clinical and neurocognitive outcome in symptomatic isovaleric acidemia

Research

Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns

Research

Toxic epidermal necrolysis, DRESS, AGEP: Do overlap cases exist?

Research

Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3

Review

The trisomy 18 syndrome