Stable isotope dilution analysis ofN‐acetylaspartic acid in CSF, blood, urine and amniotic fluid: Accurate postnatal diagnosis and the potential for prenatal diagnosis of canavan disease

Abstract

A sensitive and selective analytical technique is described for the determination ofN-acetylaspartic acid in body fluids using stable isotope dilution in combination with positive chemical ionization mass spectrometry with selected ion monitoring. Control mean and ranges have been established: in urine 19.5 and 6.6–35.4 µmol/mmol creat.; in plasma 0.44 and 0.17–0.81 µmol/L; in cerebrospinal fluid 1.51 and 0.25–2.83 µmol/L; and in amniotic fluid 1.27 and 0.30–2.55 µmol/L. In a patient with Canavan disease,N-acetylaspartic acid concentration was elevated 80-fold in urine and 20-fold in plasma compared to the control means. A subsequent pregnancy of the mother was monitored and theN-acetylaspartic acid concentration in the amniotic fluid was within the control range and a healthy child was born.