| Title: | Clinical spectrum of succinic semialdehyde dehydrogenase deficiency |
| Author(s): | Pearl PL; Gibson KM; Acosta MT; Vezina LG; Theodore WH; Rogawski MA; Novotny EJ; Gropman A; Conry JA; Berry GT; Tuchman M; |
| Address: | "Department of Neurology, Children's National Medical Center, George Washington University School of Health Sciences, Washington, DC 20010-2970, USA. ppearl@cnmc.org" |
| DOI: | 10.1212/01.wnl.0000059549.70717.80 |
| ISSN/ISBN: | 1526-632X (Electronic) 0028-3878 (Linking) |
| Abstract: | "Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting CNS gamma-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 chromatography-mass 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" |
| Keywords: | "Adolescent Adult Aldehyde Oxidoreductases/*deficiency Autistic Disorder/etiology Child Child, Preschool Cohort Studies Electroencephalography Female Genes, Recessive Globus Pallidus/pathology Humans Hydroxybutyrates/*urine Infant Intellectual Disability/e;" |
| Notes: | "MedlinePearl, P L Gibson, K M Acosta, M T Vezina, L G Theodore, W H Rogawski, M A Novotny, E J Gropman, A Conry, J A Berry, G T Tuchman, M eng NS-40270/NS/NINDS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2003/05/14 Neurology. 2003 May 13; 60(9):1413-7. doi: 10.1212/01.wnl.0000059549.70717.80" |
