Clinical spectrum of succinic semialdehyde dehydrogenase deficiency

Phillip L. Pearl, K. M. Gibson, M. T. Acosta, L. G. Vezina, W. H. Theodore, Michael A Rogawski, E. J. Novotny, A. Gropman, J. A. Conry, G. T. Berry, M. Tuchman

Research output: Contribution to journalArticlepeer-review

148 Scopus citations


Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting CNS γ-aminobutyric acid (GABA) degradation. SSADH, in conjunction with GABA transaminase, converts GABA to succinate. In the absence of SSADH, GABA is converted to 4-OH-butyrate. The presence of 4-OH-butyrate, a highly volatile compound, may be undetected on routine organic acid analysis. Urine organic acid testing was modified at the authors' institution in 1999 to screen for the excretion of 4-OH-butyrate by selective ion monitoring gas chromatographymass spectrometry in addition to total ion chromatography. Since then, five patients with 4-hydroxybutyric aciduria have been identified. The authors add the clinical, neuroimaging, and EEG findings from a new cohort of patients to 51 patients reported in the literature with clinical details. Ages ranged from 1 to 21 years at diagnosis. Clinical findings include mild-moderate mental retardation, disproportionate language dysfunction, hypotonia, hyporeflexia, autistic behaviors, seizures, and hallucinations. Brain MRI performed in five patients at the authors' institution revealed symmetric increased T2 signal in the globus pallidi. SSADH deficiency is an under-recognized, potentially manageable neurometabolic disorder. Urine organic acid analysis should include a sensitive method for the detection of 4-hydroxybutyrate and should be obtained from patients with mental retardation or neuropsychiatric disturbance of unknown etiology.

Original languageEnglish (US)
Pages (from-to)1413-1417
Number of pages5
Issue number9
StatePublished - May 13 2003
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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