Summary
We Report our cumulative experience for the prenatal diagnosis of succinic semialdehyde dehydrogenase (SSADH) deficiency in seven ‘at-risk’ pregnancies from four unrelated families. Prenatal diagnosis was performed by determination of 4-hydroxybutyric acid (4-HBA) concentration in amniotic fluid using isotope-dilution gas chromatography-mass spectrometry in conjunction with assay of SSADH activity in biopsied chorionic villus and/or cultured amniocytes. In three of four pregnancies predicted as affected, confirmation was obtained by demonstration of deficient SSADH activity in fetal tissues. Our results suggest that determination of 4-HBA concentration in amniotic fluid combined with enzyme determination in cultured or biopsied tissue represents a reliable method for the prenatal diagnosis of SSADH deficiency.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Chambliss KL, Gibson KM (1992) Succinic semialdehyde dehydrogenase from mammalian brain: subunit analysis using polyclonal antiserum.Int J Biochem 24: 1493–1499.
Chambliss KL, Lee CF, Ogier H, Rabier D, Jakobs C, Gibson KM (1993) Enzymatic and immunological demonstration of normal and defective succinic semialdehyde dehydrogenase activity in fetal brain, liver and kidney.J Inher Metab Dis 16: 523–526.
Gibson KM, Aramaki S, Sweetman L et al (1990) Stable isotope dilution analysis of 4-hydroxybutyric acid: an accurate method for quantification in physiological fluids and the prenatal diagnosis of 4-hydroxybutyric aciduria.Biomed Environ Mass Spectrom 19: 89–93.
Gibson KM, Lee CF, Chambliss KL et al (1991) 4-Hydroxybutyric aciduria: application of a fluorometric assay to the determination of succinic semialdehyde dehydrogenase activity in extracts of cultured human lymphoblasts.Clin Chim Acta 196: 219–222 (letter).
Jakobs C, Ogier H, Rabier D, Gibson KM (1993a) Prenatal detection of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria).Prenat Diagn 13: 150 (letter)
Jakobs C, Jaeken J, Gibson KM (1993b) Inherited disorders of GABA metabolism.J Inher Metab Dis 16: 704–715.
Onkenhout W, Maaswinkel-Mooij PD, Poorthuis BJHM (1989) 4-Hydroxybutyric aciduria: further clinical heterogeneity in a new case.Eur J Pediatr 14: 194–196.
Pattarelli PP, Nyhan WL, Gibson KM (1988) Oxidation of [U14C]succinic semialdehyde in cultured human lymphoblasts: measurement of residual succinic semialdehyde dehydrogenase activity in 11 patients with 4-hydroxybutyric aciduria.Pediatr Res 24: 455–460.
Sweetman FR, Gibson KM, Sweetman L et al (1986) Activity of biotin-dependent and GABA metabolizing enzymes in chorionic villus samples: potential for 1st trimester prenatal diagnosis.Prenat Diagn 6: 187–194.
Thorburn DR, Thompson GN, Howells DW (1993) A fluorimetric assay for succinic semialdehyde dehydrogenase activity suitable for prenatal diagnosis of the enzyme deficiency.J Inher Metab Dis 16: 942–949.
Uziel G, Bardelli P, Pantaleoni C, Rimoldi M, Savoiardo M (1993) 4-Hydroxybutyric aciduria: clinical findings and vigabatrin therapy.J Inher Metab Dis 16: 520–522.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gibson, K.M., Baumann, C., Ogier, H. et al. Pre- and postnatal diagnosis of succinic semialdehyde dehydrogenase deficiency using enzyme and metabolite assays. J Inherit Metab Dis 17, 732–737 (1994). https://doi.org/10.1007/BF00712016
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00712016