Fragile X Syndrome. A pilot Proton Magnetic Resonance Spectroscopy Study in Pre-mutation carriers.

                           Purpose There is increasing evidence that neurodevelopmental differences in people with Fragile X syndrome (FraX) may be explained by differences in glutamatergic metabolism.  Pre-mutation carriers of FraX were originally considered to be unaffected although several recent reports demonstrate neuroanatomical, cognitive and emotional differences from controls.  However there are few studies on brain metabolism in premutation carriers of FraX.   Methods We used proton magnetic resonance spectroscopy  to compare neuronal integrity of a number of brain metabolites including N-Acetyl Aspartate, Creatine + Phosphocreatinine, Choline, myoInositol  and Glutamate containing substances (Glx) in 17 male premutation carriers of FraX and 16 male healthy control individuals.   Results There was no significant between-group difference in the concentration of any measured brain metabolites.  However there was a differential increase in N-acetyl aspartate with aging in premutation FraX individuals compared to controls.   Conclusions This is the first 1H-MRS study to examine premutation FraX individuals. Although we demonstrated no difference in the concentration of any of the metabolites examined between the groups, this may be due to the large age ranges included in the two samples. The differential increase in NAA levels with aging which may reflect an abnormal synaptic pruning process.