Document Detail


Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency.
MedLine Citation:
PMID:  12891656     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare disorder characterized by an inborn error of the catabolism of the inhibitory neurotransmitter GABA. Because of the deficiency of SSADH, the final enzyme of the GABA degradation pathway, the substrate, succinic semialdehyde, is shunted towards production of 4-hydroxybutyric acid (gamma-hydroxybutyric acid). Elevations of gamma-hydroxybutyric acid can be detected in the physiologic fluids of patients with SSADH deficiency, and forms the mainstay of diagnosis. The clinical features of SSADH deficiency include nonspecific neurologic manifestations such as mental retardation/developmental delay, absent speech, hypotonia, nonprogressive ataxia, features of autism or pervasive developmental delay, developmental language delay (dyspraxia, receptive, and expressive delays), and occasionally, seizures. Although the metabolic pathway has been established, it is not known whether insufficient GABA and/or excess gamma-hydroxybutyric acid contribute to the disease phenotype. Pharmacological therapy in patients with this disorder has been limited to vigabatrin, an anticonvulsant that blocks GABA transaminase. This review will discuss therapeutic options in SSADH deficiency, on the basis of patient experience, and preliminary work using a murine model. Finally, a discussion of adjunctive therapies will be included.
Authors:
Andrea Gropman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Annals of neurology     Volume:  54 Suppl 6     ISSN:  0364-5134     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2003  
Date Detail:
Created Date:  2003-07-31     Completed Date:  2003-12-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S66-72     Citation Subset:  IM    
Affiliation:
Neurogenetics Branch, Section on Neuronal Migration, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. gropmana@ninds.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Aldehyde Oxidoreductases / deficiency*,  genetics*
Amino Acid Metabolism, Inborn Errors / drug therapy*,  genetics*
Animals
Anticonvulsants / adverse effects,  therapeutic use*
Clinical Trials as Topic
Drug Therapy, Combination
Humans
Succinate-Semialdehyde Dehydrogenase
Vigabatrin / adverse effects,  therapeutic use*
gamma-Aminobutyric Acid / metabolism*
Chemical
Reg. No./Substance:
0/Anticonvulsants; 56-12-2/gamma-Aminobutyric Acid; 60643-86-9/Vigabatrin; EC 1.2.-/Aldehyde Oxidoreductases; EC 1.2.1.24/ALDH5A1 protein, human; EC 1.2.1.24/Succinate-Semialdehyde Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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