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.
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.
Jakobs
C
C
Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands.
ten Brink
H J
HJ
Langelaar
S A
SA
Zee
T
T
Stellaard
F
F
Macek
M
M
Srsnová
K
K
Srsen
S
S
Kleijer
W J
WJ
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
D001224:Aspartic Acid; C000179:N-acetylaspartate; D000581:Amidohydrolases; C019751:aspartoacylase