Follow-Up of a Child with Hypoacetylaspartia

Abstract

We provide a 5-year follow-up of a patient previously reported to have no NAA signal on neurospectroscopy. At 8 years this boy was found to have profound neurological dysfunction: he had truncal ataxia, no expressive speech, behaviour abnormalities, secondary microcephaly and cognitive achievements corresponding to less than 12 months of age. He started to have generalized seizures at 5 years 9 months. Although not directly proven we assume an inborn error of NAA metabolism, possibly a defect of the anabolic enzyme L-aspartate N-acetyltransferase (EC 2.3.1.17).

Magnetic resonance imaging - magnetic resonance spectroscopy - N-acetylaspartate - N-acetylaspartylglutamate - capillary electrophoresis - hypoacetylaspartia

References

• 1 Arnold D L, de Stefano N, Matthews P M, Trapp B D. N-Acetylaspartate: usefulness as an indicator of viable neuronal tissue.  Ann Neurol. 2001;  50 823-825
• 2 Baslow M H. The existence of molecular water pumps in the nervous system: a review of the evidence.  Neurochem Int. 1999;  34 77-90
• 3 Baslow M H. N-Acetylaspartate in the vertebrate brain: metabolism and function.  Neurochem Res. 2003;  28 941-953
• 4 Berlinguet L, Laliberte M. Metabolism of N-acetyl-L-aspartic acid in mice.  Can J Biochem. 1966;  44 783-789
• 5 Bjartmar C, Battistuta J, Terada N, Dupree E, Trapp B D. N-Acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve.  Ann Neurol. 2002;  51 51-58
• 6 Briellmann R S, Berkovic S F, Syngeniotis A, King M A, Jackson G D. Seizure-associated hippocampal volume loss: a longitudinal magnetic resonance study of temporal lobe epilepsy.  Ann Neurol. 2002;  51 641-644
• 7 Brovia V, Ricciardi A, Barbeito L. N-Acetyl-aspartylglutamate (NAAG) in human cerebrospinal fluid: determination by high performance liquid chromatography, and influence of biological variables.  Amnio Acids. 1995;  9 175-184
• 8 Burlina A P, Ferrari V, Facci L, Skaper S D, Burlina A B. Mast cells contain large quantities of secretagogue-sensitive N-acetylaspartate.  J Neurochem. 1997;  69 1314-1317
• 9 Burlina A P, Ferrari V, Divry P, Gradowska W, Jakobs C, Bennett M J. et al . N-Acetylaspartylglutamate in Canavan disease: an adverse effector?.  Eur J Pediatr. 1999;  158 406-409
• 10 Burlina A P, Ferrari V, Burlina A B, Bertini E, Boespflug-Tanguy O. Increased levels of N-acetylaspartylglutamate in CSF and urine of patients with Pelizaeus-Merzbacher disease.  J Inherit Metabol Dis. 2000;  23 (Suppl 1) 213-[abstract]
• 11 Burns S P, Chalmers R A, West R J, Iles R A. Measurement of human brain aspartate N-acetyl transferase flux in vivo.  Biochem Soc Trans. 1992;  20 107S
• 12 Cangro C B, Namboodiri M A, Sklar L A, Corigliano-Murphy A, Neale J H. Immunohistochemistry and biosynthesis of N-acetylaspartylglutamate in spinal sensory ganglia.  J Neurochem. 1987;  49 1579-1588
• 13 Danielsen E R, Ross B. Magnetic Resonance Spectroscopy Diagnosis of Neurological Diseases. Monticello; Dekker 1999
• 14 deGrauw T J, Salomons G S, Cecil K M, Chuck G, Newmeyer A, Schapiro M B. et al . Congenital creatine transporter deficiency.  Neuropediatrics. 2002;  33 232-238
• 15 Engelke U F, Liebrand-van Sambeek M L, de Jong J G, Leroy J G, Morava E, Smeitink J A. et al . N-Acetylated metabolites in urine: proton nuclear magnetic resonance spectroscopic study on patients with inborn errors of metabolism.  Clin Chem. 2004;  50 58-66
• 16 Faull K F, Rafie R, Pascoe N, Marsh L, Pfefferbaum A. N-Acetylaspartic acid (NAA) and N-acetylaspartylglutamic acid (NAAG) in human ventricular, subarachnoid, and lumbar cerebrospinal fluid.  Neurochem Res. 1999;  24 1249-1261
• 17 Gonen O, Catalaa I, Babb J S, Ge Y, Mannon L J, Kolson D L. et al . Total brain N-acetylaspartate: a new measure of disease load in MS.  Neurology. 2000;  54 15-19
• 18 Guarda A S, Robinson M B, Ory-Lavollee L, Forloni G L, Blakely R D, Coyle J T. Quantitation of N-acetyl-aspartyl-glutamate in microdissected rat brain nuclei and peripheral tissues: findings with a novel liquid phase radioimmunoassay.  Brain Res. 1988;  427 223-231
• 19 Jenkins B G, Kraft E. Magnetic resonance spectroscopy in toxic encephalopathy and neurodegeneration.  Curr Opin Neurol. 1999;  12 753-760
• 20 Kalra S, Arnold D L, Cashman N R. Biological markers in the diagnosis and treatment of ALS.  J Neurol Sci. 1999;  165 (Suppl 1) S27-32
• 21 Madhavarao C N, Chinopoulos C, Chandrasekaran K, Namboodiri M A. Characterization of the N-acetylaspartate biosynthetic enzyme from rat brain.  J Neurochem. 2003;  86 824-835
• 22 Martin E, Capone A, Schneider J, Hennig J, Thiel T. Absence of N-acetylaspartate in the human brain: impact on neurospectroscopy?.  Ann Neurol. 2001;  49 518-521
• 23 Sullivan E V, Adalsteinsson E, Spielman D M, Hurd R E, Pfefferbaum A. N-Acetylaspartate - a marker of neuronal integrity.  Ann Neurol. 2001;  50 823 author reply 824-825
• 24 Truckenmiller M E, Namboodiri M A, Brownstein M J, Neale J H. N-Acetylation of L-aspartate in the nervous system: differential distribution of a specific enzyme.  J Neurochem. 1985;  45 1658-1662
• 25 Tyson R L, Sutherland G R. Labeling of N-acetylaspartate and N-acetylaspartylglutamate in rat neocortex, hippocampus and cerebellum from [^{1 - 13} C]glucose.  Neurosci Lett. 1998;  251 181-184
• 26 van der Knaap M S, Verhoeven N M, Maaswinkel-Mooij P, Pouwels P J, Onkenhout W, Peeters E A. et al . Mental retardation and behavioral problems as presenting signs of a creatine synthesis defect.  Ann Neurol. 2000;  47 540-543
• 27 Vermathen P, Ende G, Laxer K D, Walker J A, Knowlton R C, Barbaro N M. et al . Temporal lobectomy for epilepsy: recovery of the contralateral hippocampus measured by ¹H MRS.  Neurology. 2002;  59 633-636
• 28 Wevers R A, Engelke U, Wendel U, de Jong J G, Gabreels F J, Heerschap A. Standardized method for high-resolution ¹H-NMR of cerebrospinal fluid.  Clin Chem. 1995;  41 744-751