Threshold effect of urinary glycosaminoglycans and the walk test as indicators of disease progression in a survey of subjects with Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

Abstract

A cross-sectional survey in individuals affected with the lysosomal storage disease Mucopolysaccharidosis VI (MPS VI) was conducted to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of the disease. The survey evaluated 121 bona fide MPS VI-affected individuals over the age of 4 years from 15 countries across the Americas, Europe, and Australasia representing greater than 10% of the estimated world prevalence of the disease. A medical history, complete physical exam, urinary GAG determination, and assessment of several clinical measures related to physical endurance, pulmonary function, joint range of motion, strength, and quality of life were completed for each participant. Although a wide variation in clinical presentation was observed, several general findings were obtained reflecting progression of the disease. Impaired physical endurance, as measured by the distance achieved in a 6-min walk, could be demonstrated across all age groups of MPS VI-affected individuals. High urinary GAG values (>200 mug/mg creatinine) were associated with an accelerated clinical course comprised of age-adjusted short stature and low body weight, impaired endurance, compromised pulmonary function, and reduced joint range of motion. An unexpected result was the predominance of urinary GAG values <100 mug/mg creatinine for those participants over the age of 20 years. Pending the collection of longitudinal data, these results suggest that urinary GAG levels predict clinical morbidity, and longer-term survival is associated with urinary GAG levels below a threshold of 100 mug/mg creatinine.

Growth Charts for Individuals with Mucopolysaccharidosis VI (Maroteaux–Lamy Syndrome)

“…In the MPS VI population, height for age was previously reported to correspond with the pre-ERT uGAG levels (Swiedler et al 2005;Decker et al 2010). However, uGAG levels are naturally high in unaffected individuals during infancy (Gallegos-Arreola et al 2000;Gray et al 2007), and pretreatment uGAG levels in infants with MPS VI do not correlate closely with disease severity.…”

“…The 207 patients 25 years of age with available pre-ERT (or within 1 month of ERT) height measurements represent approximately 19% of the estimated worldwide MPS VI population (Swiedler et al 2005); however, these numbers are an underestimation of the true prevalence as the referenced numbers are based on the estimates from the USA, Europe, and Brazil. The patient population in this dataset included patients from many countries and, thus, supports wide applicability of these MPS VI growth charts.…”

“…We pooled cross-sectional and longitudinal height for age data from patients who participated in the MPS VI crosssectional Survey Study done in 2001-2002(Swiedler et al 2005; clinical trials and their extension programs, including phase 1/2, phase 2, phase 3 (Harmatz et al 2004;Harmatz et al 2005;Harmatz et al 2006;Harmatz et al 2008), and a phase 4 study ; the MPS VI clinical surveillance program (CSP; ClinicalTrials.gov: NCT00214773); and the Resurvey Study (Giugliani et al 2014) to construct growth charts for patients with the MPS VI disorder. Patients treated with galsulfase (recombinant human arylsulfatase B; rhASB; Naglazyme ® ; an enzyme replacement therapy [ERT] for MPS VI) or patients status post hematopoietic stem cell transplant (HSCT) were excluded from this analysis.…”

Spondyloepiphyseal Dysplasias and Bilateral Legg-Calvé-Perthes Disease: Diagnostic Considerations for Mucopolysaccharidoses

“…Intelligence is normal for MPS IVA patients as well. MPS VI patients present along a spectrum of severity with younger more severe patients presenting earlier (Swiedler et al 2005). Among 326 patients in the International Morquio A Registry, the mean age of onset of symptoms was 2.1 years, and the mean age at diagnosis is 4.7 years of age (Montano et al 2007).…”

“…MPS diseases are rare with the overall incidence of MPS disorders ranging from 3.5 to 4.5 per 100,000 (Krabbi et al 2012). The estimated incidence of MPS VI is 1 in 340,000 live births although it may be under recognized (Swiedler et al 2005). The estimated incidence of MPS IV (type A) is 1 in 169,000 (Meikle et al 1999).…”