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

Authors :
Hogema BM
Akaboshi S
Taylor M
Salomons GS
Jakobs C
Schutgens RB
Wilcken B
Worthington S
Maropoulos G
Grompe M
Gibson KM
Source :
Molecular genetics and metabolism [Mol Genet Metab] 2001 Mar; Vol. 72 (3), pp. 218-22.
Publication Year :
2001

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 (gamma-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.<br /> (Copyright 2001 Academic Press.)

Details

Language :
English
ISSN :
1096-7192
Volume :
72
Issue :
3
Database :
MEDLINE
Journal :
Molecular genetics and metabolism
Publication Type :
Academic Journal
Accession number :
11243727
Full Text :
https://doi.org/10.1006/mgme.2000.3145