Quantifying medical manifestations in Hurler syndrome with the infant physical symptom score: associations with long-term physical and adaptive outcomes

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Abstract

Background: A physical symptom score (PSS) for the mucopolysaccharidosis (MPS) disorders has been developed to quantitate the somatic burden of disease across multiple organ systems. Studies have demonstrated the sensitivity and its relationship to age, IQ and adaptive functioning of the PSS in older children. With the onset of newborn screening, there is an increased need to characterize the somatic symptoms in the earliest stages of life, especially for young children under 36 months of age. Consequently, a new scale, Infant Physical Symptom Score (IPSS), was developed to score physical symptoms in infants and toddlers. Objective: Part I. To create a measure to quantify somatic burden in patients with MPS disorders under 36 months of age. The IPSS assess outcomes and changes in somatic disease in individuals with MPS disorders diagnosed very early in life. Part II. To determine the relationship between IPSS and other measures to evaluate its validity and utility, a) we evaluated the relationship between the IPSS and PSS in the same patients with MPS I over time to determine if the two scales are measuring the same concepts, and b) we evaluated the association between IPSS and a functional adaptive measure over time with a focus on the age at first treatment (under 36 months) to determine if the IPSS has predictive value. Methods: Part I. The Infant Physical Symptom Score (IPSS) for the infant population in MPS disorders was established using data from 39 patients enrolled in the Lysosomal Disease Network longitudinal MPS I study (U54NS065768). All of these patients had Hurler syndrome (MPS IH) and underwent hematopoietic stem cell transplant (HSCT) at the University of Minnesota. Items for the IPSS were selected by reviewing CRFs prepared for the MPS I longitudinal study and examining medical records of these patients prior to HSCT based on the knowledge gained from the development of the PSS. Part II. Of those 39 patients, a subset of 19 were all seen 9 to 12 years post HSCT. Having retrospectively calculated their IPSS prior to HSCT, we categorized them by age at HSCT, and examined their most recent PSS along with Composite and Daily Living Skills scores on the Vineland Adaptive Behavior Scales – Second Edition (VABS-II). Results and conclusion: The total score on the IPSS collected prior to transplant differed by patient's age at transplant, as expected in this progressive condition. Those transplanted at ≤12 months of age had a mean score of 7.4, which was significantly lower, suggesting less somatic disease burden, compared to those transplanted at >12 to ≤24 months (mean 11.8) and > 24 to ≤36 months (mean 13.6). Higher IPSS reflects more evidence of somatic disease burden and lower IPSS reflects less evidence of disease burden. Nine to 12 years later, the severity level as measured by the PSS was comparable to severity on the IPSS suggesting that the two scales are measuring similar concepts. Retrospectively calculated pre-transplant IPSS were negatively associated with higher VABS-II Composite scores 9–12 years later (p value-0.015) and to a lesser extent Daily Living Skills scores (p value-0.081). We conclude that the IPSS appears to be a useful approach to quantifying the somatic disease burden of MPS IH patients under 36 months of age.

Original languageEnglish (US)
Pages (from-to)22-27
Number of pages6
JournalMolecular Genetics and Metabolism
Volume136
Issue number1
DOIs
StatePublished - May 2022

Bibliographical note

Funding Information:
The Lysosomal Disease Network (LDN) U54-NS065768 is a part of the National Institute of Health (NIH) Rare Diseases Clinical Research Network, supported through collaboration between the NIH Office of Rare Diseases Research at the National Center for Advancing Translational Science, the National Institute of Neurological Disorders and Stroke (NINDS), and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This project was supported in part (Dr. Rudser) by the National Center for Advancing Translational Sciences , National Institutes of Health , through University of Minnesota CTSI Grant Number NCATS UL1TR000114 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or CTSI.

Funding Information:
The Lysosomal Disease Network (LDN) U54-NS065768 is a part of the National Institute of Health (NIH) Rare Diseases Clinical Research Network, supported through collaboration between the NIH Office of Rare Diseases Research at the National Center for Advancing Translational Science, the National Institute of Neurological Disorders and Stroke (NINDS), and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This project was supported in part (Dr. Rudser) by the National Center for Advancing Translational Sciences, National Institutes of Health, through University of Minnesota CTSI Grant Number NCATS UL1TR000114. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or CTSI.We are grateful to all the research participants and their families. We thank Brenda Diethelm-Okita, David Erickson in the Lysosomal Disease Network office at the University of Minnesota for administrative assistance. We are very thankful for the support provided by the National MPS Society, Ryan Foundation for Orphan Disease Research and Center for Neurobehavioral Development (CNBD).

Funding Information:
We are grateful to all the research participants and their families. We thank Brenda Diethelm-Okita, David Erickson in the Lysosomal Disease Network office at the University of Minnesota for administrative assistance. We are very thankful for the support provided by the National MPS Society , Ryan Foundation for Orphan Disease Research and Center for Neurobehavioral Development (CNBD).

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

  • Adaptive behavior
  • Hematopoietic stem cell transplant
  • Hurler syndrome
  • Infant physical symptom score
  • Physical symptom score
  • Somatic burden of disease

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