Quantification of N-acetylglucosamine-asparagine (GlcNAc-Asn) in the brain using MR Spectroscopy in non Aspartylglucosaminuria patients

aspartylglucosaminuria (aGu) is a devastating neurodegenerative lysosomal storage disease (LSD) affecting children and young adults. The only available treatments are palliative care and supportive developmental therapies. aGu is caused by deficiency of the lysosomal enzyme aspartylglucosaminadase (aGa). This is a secreted lysosomal enzyme that cleaves the glycoprotein bond between sugar residues and proteins. Patients present with early developmental delay, plateau of development in adolescence, and regression in early adulthood [1,2]. adult-onset epilepsy, recurrent respiratory and skin infections, and connective tissue problems are also reported [3-5]. Due to a founder effect, most patients are of Finnish descent, however, variants have been identified worldwide. aGu is a particularly attractive disease to treat via gene therapy for two reasons: 1) it has a large intervention window because it is a slowly progressive neurodegenerative disorder and 2) there are robust[See protocol for complete text]