title: Visual evoked potentials in succinate semialdehyde dehydrogenase (SSADH) deficiency.
abstract: 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.
authors.affiliation: Department of Medical and Surgical Pediatrics, Unit of Infantile Neuropsychiatry, University Hospital of Messina, via Consolare Valeria, Messina, 98125, Italy. gabrielladirosa@hotmail.com
authors.forename: G
authors.initials: G
authors.lastname: Di Rosa
authors.forename: P
authors.initials: P
authors.lastname: Malaspina
authors.forename: P
authors.initials: P
authors.lastname: Blasi
authors.forename: C
authors.initials: C
authors.lastname: Dionisi-Vici
authors.forename: C
authors.initials: C
authors.lastname: Rizzo
authors.forename: G
authors.initials: G
authors.lastname: Tortorella
authors.forename: S R
authors.initials: SR
authors.lastname: Crutchfield
authors.forename: K M
authors.initials: KM
authors.lastname: Gibson
mesh_terms: D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D002208:Caproates / Q000652:urine; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities; D005074:Evoked Potentials, Visual; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates / Q000652:urine; D008297:Male; D009154:Mutation; D050644:Succinate-Semialdehyde Dehydrogenase / Q000172:deficiency* / Q000235:genetics
chemical_list: D002208:Caproates; D006885:Hydroxybutyrates; C111420:4-hydroxybutyric acid; C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase