Levels of glycosaminoglycans in the cerebrospinal fluid of healthy young adults, surrogate-normal children, and Hunter syndrome patients with and without cognitive impairment

Christian J Hendriksz; Joseph Muenzer; Adeline Vanderver; Jonathan M Davis; Barbara K Burton; Nancy J Mendelsohn; Nan Wang; Luying Pan; Arian Pano; Ann J Barbier

doi:10.1016/j.ymgmr.2015.11.001

Levels of glycosaminoglycans in the cerebrospinal fluid of healthy young adults, surrogate-normal children, and Hunter syndrome patients with and without cognitive impairment

Mol Genet Metab Rep. 2015 Nov 9:5:103-106. doi: 10.1016/j.ymgmr.2015.11.001. eCollection 2015 Dec.

Authors

Christian J Hendriksz¹, Joseph Muenzer², Adeline Vanderver³, Jonathan M Davis⁴, Barbara K Burton^{5

6}, Nancy J Mendelsohn^{7

8}, Nan Wang⁹, Luying Pan⁹, Arian Pano⁹, Ann J Barbier⁹

Affiliations

¹ The Mark Holland Metabolic Unit, Salford Royal NHS Foundation Trust, Salford M6 8HD, United Kingdom.
² Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Center for Genetic Medicine Research, Children's Research Institute, Children's National Health System, Washington, DC, 20010, USA.
⁴ Division of Newborn Medicine, Floating Hospital for Children at Tufts Medical Center, Boston, MA 02111, USA.
⁵ Division of Genetics, Birth Defects and Metabolism, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
⁶ The Ann & Robert H. Lurie Children's Hospital, Chicago, IL 60611, USA.
⁷ Department of Medical Genetics, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA.
⁸ Division of Medical Genetics, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA.
⁹ Shire, 300 Shire Way, Lexington, MA 02421, USA.

Abstract

In mucopolysaccharidoses (MPS), glycosaminoglycans (GAG) accumulate in tissues. In MPS II, approximately two-thirds of patients are cognitively impaired. We investigated levels of GAG in cerebrospinal fluid (CSF) in different populations from four clinical studies (including NCT00920647 and NCT01449240). Data indicate that MPS II patients with cognitive impairment have elevated levels of CSF GAG, whereas those with the attenuated phenotype typically have levels falling between those of the cognitively affected patients and healthy controls.

Keywords: Cerebrospinal fluid; Cognitive impairment; Glycosaminoglycans; Idursulfase; Inherited metabolic disease; Lysosomal storage disease; Mucopolysaccharidosis II.