title: Stable isotope dilution analysis of N-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 of N-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 mumol/mmol creat.; in plasma 0.44 and 0.17-0.81 mumol/L; in cerebrospinal fluid 1.51 and 0.25-2.83 mumol/L; and in amniotic fluid 1.27 and 0.30-2.55 mumol/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 the N-acetylaspartic acid concentration in the amniotic fluid was within the control range and a healthy child was born.
authors.affiliation: Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: H J
authors.initials: HJ
authors.lastname: ten Brink
authors.forename: S A
authors.initials: SA
authors.lastname: Langelaar
authors.forename: T
authors.initials: T
authors.lastname: Zee
authors.forename: F
authors.initials: F
authors.lastname: Stellaard
authors.forename: M
authors.initials: M
authors.lastname: Macek
authors.forename: K
authors.initials: K
authors.lastname: Srsnová
authors.forename: S
authors.initials: S
authors.lastname: Srsen
authors.forename: W J
authors.initials: WJ
authors.lastname: Kleijer
mesh_terms: D000581:Amidohydrolases / Q000172:deficiency*; D000653:Amniotic Fluid / Q000737:chemistry*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000652:urine; D001826:Body Fluids / Q000737:chemistry*; D005260:Female; D006801:Humans; D007201:Indicator Dilution Techniques; D007223:Infant; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012016:Reference Values
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D000581:Amidohydrolases; C019751:aspartoacylase