Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
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Query: UNIPROT:P80404 (
GABA transaminase
)
786
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Inherited disorders of gamma-aminobutyric acid (GABA) metabolism include succinic semialdehyde dehydrogenase (SSADH) and
gamma-aminobutyric acid transaminase
(
GABA-T
) deficiencies. The clinical features, pathophysiology, diagnosis, and management of both, and an updated list of mutations in the ALDH5A1 gene, which cause SSADH deficiency, are discussed. A database of 112 individuals (71 children and adolescents, and 41 adults) indicates that developmental delay and hypotonia are the most common symptoms arising from SSADH deficiency. Furthermore, epilepsy is present in two-thirds of SSADH-deficient individuals by adulthood. Research with murine genetic models and human participants, using [
11
C] flumazenil positron emission tomography (FMZ-PET) and transcranial magnetic stimulation, have led to therapeutic trials, and the identification of additional disruptions to GABA metabolism. Suggestions for new therapies have arisen from findings of GABAergic effects on autophagy, with enhanced activation of the
mammalian target of rapamycin
(
mTOR
) pathway. Details of known pathogenic mutations in the ALDH5A1 gene, three of which have not previously been reported, are summarized here. Investigations into disorders of GABA metabolism provide fundamental insights into the mechanisms underlying epilepsy, and support the importance of developing biomarkers and clinical trials. Comprehensive definition of phenotypes arising as a result of deficiencies in both SSADH and
GABA-T
may increase our understanding of the neurophysiological consequences of a hyper-GABAergic state.
...
PMID:Inherited disorders of gamma-aminobutyric acid metabolism and advances in ALDH5A1 mutation identification. 2555 43
