Abstract
Background
We report two adult patients with succinic semialdehyde dehydrogenase deficiency,
manifesting as γ-hydroxybutyric aciduria. For both, the clinical presentation included
significant behavioral disturbances and psychosis (hallucinations, disabling anxiety,
aggressive behavior, and sleep disorder), leading to multiple therapeutic attempts.
Intervention with benzodiazepines appeared most efficacious, resulting in decreased
aggression and agitation and improvement in anxiety. A review of 56 published and
unpublished studies of SSADH-deficient patients revealed that 42% manifested behavioral
disturbances, whereas 13% (predominantly adults) displayed psychotic symptomatology.
Methods
To explore the potential biochemical basis of these behavioral abnormalities, we studied
cerebrospinal fluid derived from 13 patients, which revealed significantly elevated
GHB (65- to 230-fold), high free and total GABA (up to threefold), and low glutamine.
Results
Although within the control range, homovanillic and 5-hydroxyindoleacetic acids (end
products of dopamine and serotonin metabolism, respectively) showed a significant
linear correlation with increasing GHB concentration, suggesting enhanced dopamine
and serotonin turnover.
Conclusions
We conclude that elevated GABA combined with low glutamine suggest disruption of the
glial-neuronal glutamine/GABA/glutamate shuttle necessary for replenishment of neuronal
neurotransmitters, whereas altered dopamine and serotonin metabolism may be causally
linked to the hyperkinetic movement disorders and behavioral disturbances seen in
SSADH-deficient patients.
Keywords
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Article info
Publication history
Accepted:
January 3,
2003
Received in revised form:
October 23,
2002
Received:
July 22,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
