A Cerebrospinal Fluid Collection Study in Pediatric and Adult Patients With Hunter Syndrome

Christian J Hendriksz,Ann J Barbier,Luying Pan,Barbara K Burton,Hicham Naimy,Nan Wang,Arian Pano,Joseph Muenzer

doi:10.1177/2326409815595821

Abstract

Hunter syndrome (mucopolysaccharidosis II [MPS II]) is characterized by lysosomal glycosaminoglycan (GAG) accumulation. Although a majority of patients with MPS II experience neurocognitive involvement, few data are available on cerebrospinal fluid (CSF) GAG levels in these patients. This study measured GAG levels in CSF collected from 9 patients with MPS II, including 4 adults (aged ≥18 years) with normal cognition, and 5 children, 3 of them with cognitive impairment. The CSF total GAG levels were generally higher in the 3 patients with cognitive impairment (range 842.9-2360.9 ng/mL) versus those with normal cognitive status (range 356.8-1181.1 ng/mL). Heparan sulfate levels, as measured by mass spectrometry, generally followed a similar pattern, with patients with the severe phenotype having the highest values. These data, limited by small sample size, suggest CSF GAG levels and heparan sulfate levels may be higher in patients with cognitive impairment versus patients with cognitively intact MPS II.

Highlights

Known as mucopolysaccharidosis II (MPS II), is a rare lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase, which leads to progressive accumulation of glycosaminoglycans (GAGs), mostly heparan sulfate (HS) and dermatan sulfate (DS), in most organs and body tissues.[1]
Limited data are available on cerebrospinal fluid (CSF) GAG levels in patients with MPS II, including whether these levels differ between patients with the severe and attenuated phenotypes.[5,6]
The results of this study contribute much-needed data regarding the levels of CSF GAG and HS in pediatric and adult patients with MPS II and their association with cognitive status

Summary

Introduction

Known as mucopolysaccharidosis II (MPS II), is a rare lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase, which leads to progressive accumulation of glycosaminoglycans (GAGs), mostly heparan sulfate (HS) and dermatan sulfate (DS), in most organs and body tissues.[1] Accumulation of HS and DS affects multiple organ systems and manifests clinically as an array of signs and symptoms, including facial dysmorphism, organomegaly, joint stiffness and contractures, pulmonary dysfunction, myocardial enlargement, and valvular dysfunction, with decreased life expectancy.[2,3] An estimated two-thirds of patients have the severe phenotype characterized by cognitive impairment and death typically in the second decade of life. Limited data are available on cerebrospinal fluid (CSF) GAG levels in patients with MPS II, including whether these levels differ between patients with the severe and attenuated phenotypes.[5,6] Clarification of these factors could facilitate diagnosis and treatment of neurocognitive impairment in MPS II and contribute to understanding its pathophysiology

Methods

Results

Conclusion