Inherited disorders of GABA metabolism

C Jakobs; J Jaeken; K M Gibson

doi:10.1007/BF00711902

Back

Journal article

Open access

Peer reviewed

Inherited disorders of GABA metabolism

C Jakobs, J Jaeken and K M Gibson

Journal of inherited metabolic disease, Vol.16(4), pp.704-715

1993

DOI: https://doi.org/10.1007/BF00711902

Handle:

https://hdl.handle.net/2376/106137

PMID: 8412016

Files and links (1)

url

https://doi.org/10.1007/BF00711902View

Published (Version of record) Open

Abstract

Carnosine - analogs & derivatives

Dipeptidases - deficiency

Aldehyde Oxidoreductases - deficiency

Amino Acid Metabolism, Inborn Errors - genetics

gamma-Aminobutyric Acid - metabolism

Glutamate Decarboxylase - deficiency

Humans

Amino Acid Metabolism, Inborn Errors - cerebrospinal fluid

Carnosine - metabolism

4-Aminobutyrate Transaminase - deficiency

Succinate-Semialdehyde Dehydrogenase

Amino Acid Metabolism, Inborn Errors - enzymology

Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system, is produced from glutamic acid in a reaction catalysed by glutamic acid decarboxylase. The sequential actions of GABA-transaminase (converting GABA to succinic semialdehyde) and succinic semialdehyde dehydrogenase (oxidizing succinic semialdehyde to succinic acid) allow oxidative metabolism of GABA through the tricarboxylic acid cycle. The inherited disorders of GABA metabolism include: (1) pyridoxine-dependent seizures (?glutamic acid decarboxylase deficiency) (> 50 patients); (2) GABA-transaminase deficiency (2 patients/1 family); (3) succinic semialdehyde dehydrogenase deficiency (32 patients/21 families); and (4) homocarnosinosis associated with serum carnosinase deficiency (3 patients/1 family). Homocarnosine is a brain-specific dipeptide of GABA and L-histidine. Of these four defects, definitive enzymatic diagnoses have been made only for GABA-transaminase and succinic semialdehyde dehydrogenase deficiencies. The presumptive mode of inheritance for all disorders is autosomal recessive, and all are associated with central nervous system dysfunction. Only succinic semialdehyde dehydrogenase deficiency manifests organic aciduria, which may account for the higher number of patients identified with this disorder; identification of additional patients with some of the other disorders will require increased request for analysis of cerebrospinal fluid metabolites by paediatricians and neurometabolic specialists.

Metrics

11 Record Views

See more details

Details

Title: Inherited disorders of GABA metabolism
Creators: C Jakobs - Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands
J Jaeken
K M Gibson
Publication Details: Journal of inherited metabolic disease, Vol.16(4), pp.704-715
Academic Unit: Pharmacotherapy, Department of
Publisher: United States
Grant note: R01 NS040270 / NINDS NIH HHS
Identifiers: 99900546631501842
Language: English
Resource Type: Journal article