The natural history of MPS I: global perspectives from the MPS I Registry

Michael Beck, Pamela Arn, Roberto Giugliani, Joseph Muenzer, Torayuki Okuyama, John Taylor, Shari Fallet, Michael Beck, Pamela Arn, Roberto Giugliani, Joseph Muenzer, Torayuki Okuyama, John Taylor, Shari Fallet

Abstract

Purpose: In this study, we aimed to describe the natural history of mucopolysaccharidosis I.

Methods: Data from 1,046 patients who enrolled in the MPS I Registry as of August 2013 were available for descriptive analysis. Only data from untreated patients and data prior to treatment for patients who received treatment were considered. Age at symptom onset, diagnosis, and treatment initiation were examined by geographic region and phenotype (from most to least severe: Hurler, Hurler-Scheie, and Scheie). For each symptom, frequency and age at onset were examined.

Results: Natural history data were available for 987 patients. Most patients were from Europe (45.5%), followed by North America (34.8%), Latin America (17.3%), and Asia Pacific (2.4%). Phenotype distribution was 60.9% for Hurler, 23.0% for Hurler-Scheie, and 12.9% for Scheie (3.2% undetermined) syndromes. Median age at symptom onset for Hurler, Hurler-Scheie, and Scheie syndromes was 6 months, 1.5 years, and 5.3 years, respectively; median age at treatment initiation was 1.5 years, 8.0 years, and 16.9 years, respectively. Coarse facial features and corneal clouding were among the most common symptoms in all three phenotypes.

Conclusion: A delay between symptom onset and treatment exists, especially in patients with attenuated mucopolysaccharidosis I. A better understanding of disease manifestations may help facilitate prompt diagnosis and treatment and improve patient outcomes.

Figures

Figure 1
Figure 1
Median age of onset of symptoms, diagnosis, and treatment by phenotype. (a) All regions, (b) Asia Pacific, (c) Europe, (d) Latin America, and (e) North America. Median age in years (left axis) calculated on the basis of patients within each phenotype for whom age of symptom onset, diagnosis, or treatment was recorded. The median age in years is noted above each column. The number of patients, n, is noted below each column. In b, the median age of symptom onset is higher than the median age of diagnosis for the five Hurler–Scheie patients, even though all five had an age of symptom onset less than or equal to the age at diagnosis, because data for age of symptom onset were not available for one patient.
Figure 2
Figure 2
Prevalence and age of onset of signs and symptoms in patients with MPS I by phenotype. (a) Hurler, (b) Hurler–Scheie, and (c) Scheie. Percentages of symptom frequency are shown on the left axis. Only symptoms reported during the natural history period in at least 25% of patients with the relevant phenotype are shown. Age data are median ages in years (right axis) for those patients with the date of symptom onset recorded. MPS I, mucopolysaccharidosis type I.

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