The Morquio A Clinical Assessment Program: Baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects

Paul Harmatz; Karl Eugen Mengel; Roberto Giugliani; Vassili Valayannopoulos; Shuan Pei Lin; Rossella Parini; Nathalie Guffon; Barbara K. Burton; Christian J. Hendriksz; John Mitchell; Ana Martins; Simon Jones; Norberto Guelbert; Ashok Vellodi; Carla Hollak; Peter Slasor; Celeste Decker

doi:10.1016/j.ymgme.2013.01.021

The Morquio A Clinical Assessment Program: Baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects

Paul Harmatz, Karl Eugen Mengel, Roberto Giugliani, Vassili Valayannopoulos, Shuan Pei Lin, Rossella Parini, Nathalie Guffon, Barbara K. Burton, Christian J. Hendriksz, John Mitchell, Ana Martins, Simon Jones, Norberto Guelbert, Ashok Vellodi, Carla Hollak, Peter Slasor, Celeste Decker^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

117 Scopus citations

Abstract

Objectives: The objectives of this study are to quantify endurance and respiratory function and better characterize spectrum of symptoms and biochemical abnormalities in mucopolysaccharidosis IVA subjects. Methods: MorCAP was a multicenter, multinational, cross sectional study amended to be longitudinal in 2011. Each study visit required collection of medical history, clinical assessments, and keratan sulfate (KS) levels. Results: Data from the first visit of 325 subjects (53% female) were available. Mean age was 14.5. years. Mean ± SD height z-scores were - 5.6 ± 3.1 as determined by the CDC growth charts. Mean ± SD from the 6-minute-walk-test was 212.6 ± 152.2. m, revealing limitations in functional endurance testing, and 30.0 ± 24.0. stairs/min for the 3-minute-stair-climb test. Respiratory function showed limitations comparable to MPS VI patients; mean ± SD was 1.2 ± 0.9. l based on forced vital capacity and 34.8 ± 25.5. l/min based on maximum voluntary ventilation. Mean urinary keratan sulfate (uKS) was elevated for all ages, and negatively correlated with age. Higher uKS correlated with greater clinical impairment based on height z-scores, endurance and respiratory function tests. The MPS Health Assessment Questionnaire reveals impairments in mobility and activities of daily living in comparison to an age-matched control population. Conclusions: MPS IVA is a multisystem disorder with a continuum of clinical presentation. All affected individuals experience significant functional limitations and reduced quality of life. Older patients have more severe exercise and respiratory capacity limitations, and more frequent cardiac pathology illustrating the progressive nature of disease.

Original language	English (US)
Pages (from-to)	54-61
Number of pages	8
Journal	Molecular Genetics and Metabolism
Volume	109
Issue number	1
DOIs	https://doi.org/10.1016/j.ymgme.2013.01.021
State	Published - May 2013

Funding

Paul Harmatz has provided consulting services, received research grants, participated in advisory board meetings and received speaker honoraria and travel support from BioMarin Pharmaceutical Inc. Carla Hollak is an investigator of BioMarin Pharmaceutical Inc. Peter Slasor and Celeste Decker are employees and stockholders of BioMarin Pharmaceutical Inc. All other authors are investigators and/or consultants of BioMarin Pharmaceutical Inc., have received research grants from BioMarin Pharmaceutical Inc. in accordance to clinical trials hospital contracts and travel support from BioMarin Pharmaceutical Inc. The authors would like to acknowledge the patients and families who participated in this investigation and all MorCAP investigators and clinic coordinators. This study was supported, in part, with funds provided by the National Center for Research Resources , 5 M01 RR-01271 (Dr. Harmatz). Dr. Parini would like to thank Fondazione Pierfranco and Luisa Mariani of Milano for providing financial support for clinical assistance to metabolic patients. Brad Glasscock, Monica Miller, Ken Martin, Elaina Jurecki, Gina Park and Dan DiPrimeo of BioMarin Pharmaceutical Inc. provided assistance with preparing this manuscript. Medical writing was provided by Judy Wiles and layout assistance by Selma Tse both of Facet Communications with funding from BioMarin Pharmaceutical Inc.

Keywords

Endurance
GALNS
Lysosomal storage disorder
MPS
Morquio
Respiratory function

ASJC Scopus subject areas

Genetics
Endocrinology
Molecular Biology
Biochemistry
Endocrinology, Diabetes and Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ymgme.2013.01.021

Cite this

Harmatz, P., Mengel, K. E., Giugliani, R., Valayannopoulos, V., Lin, S. P., Parini, R., Guffon, N., Burton, B. K., Hendriksz, C. J., Mitchell, J., Martins, A., Jones, S., Guelbert, N., Vellodi, A., Hollak, C., Slasor, P., & Decker, C. (2013). The Morquio A Clinical Assessment Program: Baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects. Molecular Genetics and Metabolism, 109(1), 54-61. https://doi.org/10.1016/j.ymgme.2013.01.021

@article{deef2ff43f734fbb9a4f58d41c8f9c9e,

title = "The Morquio A Clinical Assessment Program: Baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects",

abstract = "Objectives: The objectives of this study are to quantify endurance and respiratory function and better characterize spectrum of symptoms and biochemical abnormalities in mucopolysaccharidosis IVA subjects. Methods: MorCAP was a multicenter, multinational, cross sectional study amended to be longitudinal in 2011. Each study visit required collection of medical history, clinical assessments, and keratan sulfate (KS) levels. Results: Data from the first visit of 325 subjects (53% female) were available. Mean age was 14.5. years. Mean ± SD height z-scores were - 5.6 ± 3.1 as determined by the CDC growth charts. Mean ± SD from the 6-minute-walk-test was 212.6 ± 152.2. m, revealing limitations in functional endurance testing, and 30.0 ± 24.0. stairs/min for the 3-minute-stair-climb test. Respiratory function showed limitations comparable to MPS VI patients; mean ± SD was 1.2 ± 0.9. l based on forced vital capacity and 34.8 ± 25.5. l/min based on maximum voluntary ventilation. Mean urinary keratan sulfate (uKS) was elevated for all ages, and negatively correlated with age. Higher uKS correlated with greater clinical impairment based on height z-scores, endurance and respiratory function tests. The MPS Health Assessment Questionnaire reveals impairments in mobility and activities of daily living in comparison to an age-matched control population. Conclusions: MPS IVA is a multisystem disorder with a continuum of clinical presentation. All affected individuals experience significant functional limitations and reduced quality of life. Older patients have more severe exercise and respiratory capacity limitations, and more frequent cardiac pathology illustrating the progressive nature of disease.",

keywords = "Endurance, GALNS, Lysosomal storage disorder, MPS, Morquio, Respiratory function",

author = "Paul Harmatz and Mengel, {Karl Eugen} and Roberto Giugliani and Vassili Valayannopoulos and Lin, {Shuan Pei} and Rossella Parini and Nathalie Guffon and Burton, {Barbara K.} and Hendriksz, {Christian J.} and John Mitchell and Ana Martins and Simon Jones and Norberto Guelbert and Ashok Vellodi and Carla Hollak and Peter Slasor and Celeste Decker",

note = "Funding Information: The authors would like to acknowledge the patients and families who participated in this investigation and all MorCAP investigators and clinic coordinators. This study was supported, in part, with funds provided by the National Center for Research Resources , 5 M01 RR-01271 (Dr. Harmatz). Dr. Parini would like to thank Fondazione Pierfranco and Luisa Mariani of Milano for providing financial support for clinical assistance to metabolic patients. Brad Glasscock, Monica Miller, Ken Martin, Elaina Jurecki, Gina Park and Dan DiPrimeo of BioMarin Pharmaceutical Inc. provided assistance with preparing this manuscript. Medical writing was provided by Judy Wiles and layout assistance by Selma Tse both of Facet Communications with funding from BioMarin Pharmaceutical Inc.",

year = "2013",

month = may,

doi = "10.1016/j.ymgme.2013.01.021",

language = "English (US)",

volume = "109",

pages = "54--61",

journal = "Molecular Genetics and Metabolism",

issn = "1096-7192",

publisher = "Academic Press Inc.",

number = "1",

}

Harmatz, P, Mengel, KE, Giugliani, R, Valayannopoulos, V, Lin, SP, Parini, R, Guffon, N, Burton, BK, Hendriksz, CJ, Mitchell, J, Martins, A, Jones, S, Guelbert, N, Vellodi, A, Hollak, C, Slasor, P & Decker, C 2013, 'The Morquio A Clinical Assessment Program: Baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects', Molecular Genetics and Metabolism, vol. 109, no. 1, pp. 54-61. https://doi.org/10.1016/j.ymgme.2013.01.021

TY - JOUR

T1 - The Morquio A Clinical Assessment Program

T2 - Baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects

AU - Harmatz, Paul

AU - Mengel, Karl Eugen

AU - Giugliani, Roberto

AU - Valayannopoulos, Vassili

AU - Lin, Shuan Pei

AU - Parini, Rossella

AU - Guffon, Nathalie

AU - Burton, Barbara K.

AU - Hendriksz, Christian J.

AU - Mitchell, John

AU - Martins, Ana

AU - Jones, Simon

AU - Guelbert, Norberto

AU - Vellodi, Ashok

AU - Hollak, Carla

AU - Slasor, Peter

AU - Decker, Celeste

N1 - Funding Information: The authors would like to acknowledge the patients and families who participated in this investigation and all MorCAP investigators and clinic coordinators. This study was supported, in part, with funds provided by the National Center for Research Resources , 5 M01 RR-01271 (Dr. Harmatz). Dr. Parini would like to thank Fondazione Pierfranco and Luisa Mariani of Milano for providing financial support for clinical assistance to metabolic patients. Brad Glasscock, Monica Miller, Ken Martin, Elaina Jurecki, Gina Park and Dan DiPrimeo of BioMarin Pharmaceutical Inc. provided assistance with preparing this manuscript. Medical writing was provided by Judy Wiles and layout assistance by Selma Tse both of Facet Communications with funding from BioMarin Pharmaceutical Inc.

PY - 2013/5

Y1 - 2013/5

N2 - Objectives: The objectives of this study are to quantify endurance and respiratory function and better characterize spectrum of symptoms and biochemical abnormalities in mucopolysaccharidosis IVA subjects. Methods: MorCAP was a multicenter, multinational, cross sectional study amended to be longitudinal in 2011. Each study visit required collection of medical history, clinical assessments, and keratan sulfate (KS) levels. Results: Data from the first visit of 325 subjects (53% female) were available. Mean age was 14.5. years. Mean ± SD height z-scores were - 5.6 ± 3.1 as determined by the CDC growth charts. Mean ± SD from the 6-minute-walk-test was 212.6 ± 152.2. m, revealing limitations in functional endurance testing, and 30.0 ± 24.0. stairs/min for the 3-minute-stair-climb test. Respiratory function showed limitations comparable to MPS VI patients; mean ± SD was 1.2 ± 0.9. l based on forced vital capacity and 34.8 ± 25.5. l/min based on maximum voluntary ventilation. Mean urinary keratan sulfate (uKS) was elevated for all ages, and negatively correlated with age. Higher uKS correlated with greater clinical impairment based on height z-scores, endurance and respiratory function tests. The MPS Health Assessment Questionnaire reveals impairments in mobility and activities of daily living in comparison to an age-matched control population. Conclusions: MPS IVA is a multisystem disorder with a continuum of clinical presentation. All affected individuals experience significant functional limitations and reduced quality of life. Older patients have more severe exercise and respiratory capacity limitations, and more frequent cardiac pathology illustrating the progressive nature of disease.

AB - Objectives: The objectives of this study are to quantify endurance and respiratory function and better characterize spectrum of symptoms and biochemical abnormalities in mucopolysaccharidosis IVA subjects. Methods: MorCAP was a multicenter, multinational, cross sectional study amended to be longitudinal in 2011. Each study visit required collection of medical history, clinical assessments, and keratan sulfate (KS) levels. Results: Data from the first visit of 325 subjects (53% female) were available. Mean age was 14.5. years. Mean ± SD height z-scores were - 5.6 ± 3.1 as determined by the CDC growth charts. Mean ± SD from the 6-minute-walk-test was 212.6 ± 152.2. m, revealing limitations in functional endurance testing, and 30.0 ± 24.0. stairs/min for the 3-minute-stair-climb test. Respiratory function showed limitations comparable to MPS VI patients; mean ± SD was 1.2 ± 0.9. l based on forced vital capacity and 34.8 ± 25.5. l/min based on maximum voluntary ventilation. Mean urinary keratan sulfate (uKS) was elevated for all ages, and negatively correlated with age. Higher uKS correlated with greater clinical impairment based on height z-scores, endurance and respiratory function tests. The MPS Health Assessment Questionnaire reveals impairments in mobility and activities of daily living in comparison to an age-matched control population. Conclusions: MPS IVA is a multisystem disorder with a continuum of clinical presentation. All affected individuals experience significant functional limitations and reduced quality of life. Older patients have more severe exercise and respiratory capacity limitations, and more frequent cardiac pathology illustrating the progressive nature of disease.

KW - Endurance

KW - GALNS

KW - Lysosomal storage disorder

KW - MPS

KW - Morquio

KW - Respiratory function

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The Morquio A Clinical Assessment Program: Baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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