Increased level of N-acetylaspartylglutamate (NAAG) in the CSF of a patient with Pelizaeus-Merzbacher-like disease due to mutation in the GJA12 gene.

Autosomal recessive Pelizaeus-Merzbacher-like disease 1 (PMLD1) is a hypomyelinating disorder of the central nervous system (CNS) with virtually identical phenotype to Pelizaeus-Merzbacher disease (PMD). PMLD1 is caused by mutations in GJA12 gene, PMD is due to mutations in PLP1 gene. Elevated levels of N-acetylaspartylglutamate (NAAG), the most abundant peptide neuromodulator in the human brain, have been recently reported in cerebral spinal fluid (CSF) of patients with PMD. Using capillary electrophoresis, we analyzed for the first time, the CSF from a girl with PMLD1 and detected high concentrations of NAAG. This finding confirms the hypothesis that NAAG may be involved in myelination-related processes and can be considered as a useful diagnostic marker not only for patients with the PLP1 related disorder, but also in those with Pelizaeus-Merzbacher like hypomyelinating disease due to other defined genetic causes, such as PMLD1.