Diagnosis and treatment trends in mucopolysaccharidosis I: findings from the MPS I Registry

Abstract

Our objective was to assess how the diagnosis and treatment of mucopolysaccharidosis I (MPS I) have changed over time. We used data from 891 patients in the MPS I Registry, an international observational database, to analyze ages at symptom onset, diagnosis, treatment initiation, and treatment allocation (hematopoietic stem cell transplantation, enzyme replacement therapy with laronidase, both, or neither) over time for all disease phenotypes (Hurler, Hurler-Scheie, and Scheie syndromes). The interval between diagnosis and treatment has become shorter since laronidase became available in 2003 (gap during 2006-2009: Hurler--0.2 year, Hurler-Scheie--0.5 year, Scheie--1.4 years). However, the age at diagnosis has not decreased for any MPS I phenotype over time, and the interval between symptom onset and treatment initiation remains substantial for both Hurler-Scheie and Scheie patients (gap during 2006-2009, 2.42 and 6.71 years, respectively). Among transplanted patients, an increasing proportion received hematopoietic stem cells from cord blood (34 out of 64 patients by 2009) and was also treated with laronidase (42 out of 45 patients by 2009).

Conclusions: Despite the availability of laronidase since 2003, the diagnosis of MPS I is still substantially delayed for patients with Hurler-Scheie and Scheie phenotypes, which can lead to a sub-optimal treatment outcome. Increased awareness of MPS I signs and symptoms by primary care providers and pediatric subspecialists is crucial to initiate early treatment and to improve the quality of life of MPS I patients.

Fig. 1

Median age at symptom onset, diagnosis, and initiation of treatment. Numbers below each bar denote the number of Registry patients in each analysis and year of diagnosis. All data are as of March 2010. Median age is given in years

Fig. 2

Distribution of treatment modalities over time. Data represent all patients enrolled in the Registry as of March 2010 who report treatment with either HSCT, laronidase, or both. An additional 116 patients reported no treatment

Fig. 3

Median age at first transplant by year of first transplant in Hurler patients. All data are as of March 2010. Horizontal lines within in each box represent the median age, and dots represent the mean age. Lower and upper box edges represent the 25th and 75th percentiles; lower and upper whiskers represent the 5th and 95th percentiles

Fig. 4

Hematopoietic stem cell source by year of first HSCT in transplanted patients. Depicted are the relative proportions of various sources of stem cells used for HSCT. All data are as of March 2010

Fig. 5

Use of laronidase with HSCT by year of first treatment. First treatment is defined as either HSCT or laronidase, whichever occurred first. For all treatment periods, 92% of Registry patients who received both HSCT and laronidase received laronidase during the peri-transplant period, defined as any time during the interval 6 months before and 3 months after HSCT. All data are as of March 2010