Short Communication 74 Wamelink MMC et al. N-Acetylaspartylglutamate  Neuropediatrics 2011; 42: 7477 received 10.03.2011 accepted 12.04.2011 Bibliography DOI http://dx.doi.org/ 10.1055/s-0031-1277176 Published online: May 3, 2011 Neuropediatrics 2011; 42: 7477 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0174-304X Correspondence Nicole I. Wolf Department of Child Neurology VU University Medical Center Postbox 7057 1007 MB Amsterdam The Netherlands n.wolf@vumc.nl Key words   N-acetylaspartylglutamate   hypomyelination   white matter disorder N-Acetylaspartylglutamate in CNS Hypomyelination disease [10] and in 2 girls with severe clinical presentations and still no known genetic diagno- sis [14]. Whether NAAG would be also elevated in the CSF of patients with other dened hypomy- elinating white matter disorders, has never been investigated. We therefore decided to systemati- cally investigate CSF NAAG in all patients with hypomyelination under our care. Patients and Methods  NAAG determination 10 ǾL CSF and 20 ǾL of internal standard (IS, 10 ǾM [ 2 H 3 ] NAAG) were diluted with deionised water to a total volume of 120 ǾL in vials. Vials were mixed vigorously, put in an ultrasonic bath for 3 min and injected onto a liquid chromatography tandem mass spectrometer (LC-MS/MS) system. Liquid chromatography was performed using a 3.9 × 150 mm Symmetry C 18 HPLC column (bead size 5 Ǿm, Waters Chromatography BV, Etten- Leur, The Netherlands). An isocratic eluent of 30 % ACN/water containing 500 mg/L octylam- monium acetate as ion pair was used. The ow rate was set to 1 mL/min and was split after the analytical column in a ratio of 1:4. A volume of 5 ǾL of sample was injected onto the column and the total run time was 10 min. Detection of NAAG was carried out on an API-3000 tandem mass spectrometer (PE-Sciex) equipped with a turbo ion spray source operating in the negative mode. Introduction  Hypomyelinating white matter disorders are characterised by a substantial permanent myelin decit of the CNS. They comprise dierent disor- ders, the prototype being Pelizaeus-Merzbacher disease (PMD), an X-linked disorder due to alter- ations of PLP1, encoding the most abundant mye- lin protein, proteolipid protein 1. Clinical signs such as hypodontia or cataract have contributed to delineating new entities [13, 15]. MRI pattern recognition also helps to identify dierent enti- ties in this heterogeneous group [12]. Neverthe- less, at least half of all patients with CNS hypomyelination still remain without a denitive diagnosis. The clinical presentation of these patients is variable. Muscle hypotonia, ataxia, spasticity and learning diculties are common, but can be surprisingly mild, even in adults. Met- abolic markers for hypomyelination have long been sought to facilitate diagnosis, to allow iden- tication of new subgroups and also to under- stand the pathogenesis of these disorders. N-Acetylaspartylglutamate (NAAG) was found to be elevated in the CSF of patients with PMD and initially thought to be a valuable marker for hypomyelination, possibly even correlating with clinical severity [3]. Subsequently, high NAAG concentrations were described in patients with other hypomyelinating disorders: in a child with Pelizaeus-Merzbacher-like disease (PMLD) due to mutations in GJC2 [11], in patients with Salla Authors M. M. C. Wamelink 1 , E. Struys 1 , U. Holwerda 1 , E. A. Sistermans 2 , R. M. L. van Spaendonk 2 , D. Halley 3 , M. A. A. P. Willemsen 4 , C. Jakobs 1 , M. S. van der Knaap 5 , N. I. Wolf 5 Aliations Aliation addresses are listed at the end of the article Abstract  CSF N-acetylaspartylglutamate (NAAG) has been found to be elevated in some hypomy- elinating disorders. This study addressed the question whether it could be used as a marker for hypomyelination and as a means to dis- tinguish between hypomyelinating disorders biochemically. We have measured CSF NAAG in a cohort of 28 patients with hypomyelina- tion with known and unknown aetiology. NAAG was found to be elevated in 7 patients, but was normal in the majority, including patients with dened hypomyelinating disorders. CSF NAAG is not a universal marker of hypomyelination, and the mechanism of its elevation remains poorly understood.