Cerebrospinal fluid as a tool in the diagnosis of neurometabolic diseases: amino acid analysis before and after acid hydrolysis

Abstract

We perform systematically amino acid analysis of the CSF before and after strong acid hydrolysis in children with unexplained neurological disease. By comparing the amino acid pattern before and after hydrolysis, defects can be traced in the metabolism not only of amino acids but also of purines, peptides, N-acetylated amino acids and peptides, and probably other compounds. This method has yielded important information such as the identification of two "new" diseases, GABA transaminase deficiency and adenylosuccinase deficiency, and the discovery of a peculiar, acid-labile double peak in the CSF of patients with the transient neonatal hyperammonaemia syndrome and with urea cycle defects. This substance was subsequently identified by others as gamma-glutamylglutamine. As a consequence, we strongly recommend incorporating of this approach in the investigation of all children with unclear neurological disease.

Approach to the diagnosis of neurotransmitter diseases exemplified by the differential diagnosis of childhood-onset dystonia

“…Additional CSF analyses can be considered in patients in whom there is a high likelihood of a neurometabolic disease but in whom initial investigations produced negative results. These might include amino acids before and after acid hydrolysis,12 leukotrienes,13 and in vitro proton nuclear magnetic resonance spectroscopy providing an overall view on proton‐containing metabolites 14…”