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.
Subject(s)
Amino Acid Metabolism, Inborn Errors/physiopathology , Evoked Potentials, Visual , Succinate-Semialdehyde Dehydrogenase/deficiency , Adult , Amino Acid Metabolism, Inborn Errors/enzymology , Amino Acid Metabolism, Inborn Errors/genetics , Caproates/urine , Child , Child, Preschool , Developmental Disabilities , Female , Humans , Hydroxybutyrates/urine , Male , Mutation , Succinate-Semialdehyde Dehydrogenase/geneticsABSTRACT
Magnetic resonance imaging was used to document brain lesions symptomatic of cerebral palsy in the macaque monkey exhibiting poor motor control and periodic episodes of ocular nystagmus and convulsive twitching. Neuroanatomic deficits most likely resulted from hemorrhage or ischemic infarction at or near the time of birth. Extreme maternal dependency and retarded behavioral development were documented at 3 and 12 months of age. Both social and motor behavior improved significantly when observed at 30 months of age after therapy.