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Visual evoked potentials in succinate semialdehyde dehydrogenase (SSADH) deficiency
Author(s) -
Di Rosa G.,
Malaspina P.,
Blasi P.,
DionisiVici C.,
Rizzo C.,
Tortorella G.,
Crutchfield S. R.,
Gibson K. M.
Publication year - 2009
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-009-1154-4
Subject(s) - endocrinology , pathophysiology , gabaergic , medicine , gamma aminobutyric acid , biology , gabaa receptor , central nervous system , receptor , downregulation and upregulation , neuroscience , inhibitory postsynaptic potential , biochemistry , gene
Summary In mammals, increased GABA in the central nervous system has been associated with abnormalities of visual evoked potentials (VEPs), predominantly manifested as increased latency of the major positive component P100. Accordingly, we hypothesized that patients with a defect in GABA metabolism, succinate semialdehyde dehydrogenase (SSADH) deficiency (in whom supraphysiological levels of GABA accumulate), would manifest VEP anomalies. We evaluated VEPs on two patients with confirmed SSADH deficiency. Whereas the P100 latencies and amplitudes for binocular VEP analyses were within normal ranges for both patients, the P100 latencies were markedly delayed for left eye (OS) (and right eye (OD), patient 1) and monocular OS (patient 2): 134–147 ms; normal <118 ms. We hypothesize that elevated GABA in ocular tissue of SSADH patients leads to a use‐dependent downregulation of the major GABAergic receptor in eye, GABA C , and that the VEP recordings’ abnormalities, as evidenced by P100 latency and/or amplitude measurements, may be reflective of abnormalities within visual systems. This is a preliminary finding that may suggest the utility of performing VEP analysis in a larger sample of SSADH‐deficient patients, and encourage a neurophysiological assessment of GABA C receptor function in Aldh5a1 −/− mice to reveal new pathophysiological mechanisms of this rare disorder of GABA degradation.