Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: Increased accuracy employing DNA, enzyme, and metabolite analyses

B. M. Hogema, S. Akaboshi, M. Taylor, G. S. Salomons, C. Jakobs, Ruud B. Schutgens, B. Wilcken, S. Worthington, G. Maropoulos, M. Grompe, K. M. Gibson

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Inherited succinic semialdehyde dehydrogenase (SSADH; EC1.2.1.24; McKusick 271980) deficiency is a defect of GABA degradation which leads to accumulation of 4-hydroxybutyric acid (γ-hydroxybutyric acid; GHB) in physiologic fluids of patients. Prenatal diagnosis (PND) was performed in three at-risk pregnancies employing combinations of: (1) reverse-transcription-polymerase chain reaction (RT-PCR) and genomic DNA amplification followed by sequencing using isolated leukocytes or cultured human lymphoblasts; (2) GHB quantitation in amniotic fluid; or (3) SSADH enzyme assay in chorionic villus (CV) and/or amniocytes. In two pregnancies, all analyses were concordant for prediction of disease status in the fetus. In the third case, enzyme activity in CV (deficient) and metabolite analysis in amniotic fluid (normal) were discordant. For clarification, mutation analysis was undertaken in CV, confirming heterozygosity for the mutation previously identified in the proband. We hypothesize that delayed transit time for shipment of CV between Greece and the United States (8 days) led to enhanced degradation of heterozygous SSADH enzyme activity. Our data demonstrate the importance of combined metabolite, enzyme, and DNA analysis for increased accuracy in the PND of SSADH deficiency.

Original languageEnglish (US)
Pages (from-to)218-222
Number of pages5
JournalMolecular Genetics and Metabolism
Volume72
Issue number3
DOIs
StatePublished - Jan 1 2001

Keywords

  • 4-hydroxybutyric aciduria
  • Amniocentesis
  • Amniocytes
  • Autosomal recessive inheritance
  • Chorionic villi
  • GABA (4-aminobutyric acid)
  • Prenatal diagnosis
  • Succinic semialdehyde dehydrogenase
  • γ-hydroxybutyric acid (GHB)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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    Hogema, B. M., Akaboshi, S., Taylor, M., Salomons, G. S., Jakobs, C., Schutgens, R. B., Wilcken, B., Worthington, S., Maropoulos, G., Grompe, M., & Gibson, K. M. (2001). Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: Increased accuracy employing DNA, enzyme, and metabolite analyses. Molecular Genetics and Metabolism, 72(3), 218-222. https://doi.org/10.1006/mgme.2000.3145