Succinic Semialdehyde Dehydrogenase Deficiency: A Metabolic and Genomic Approach to Diagnosis

Authors

Kevin E Glinton
Charul Gijavanekar
Abbhirami Rajagopal
Laura P Mackay
Kirt A Martin
Phillip L Pearl
K Michael Gibson
Theresa A Wilson
V Reid Sutton
Sarah H Elsea

Publication Date

1-1-2024

Journal

Frontiers in Genetics

DOI

10.3389/fgene.2024.1405468

PMID

39011401

PMCID

PMC11247174

PubMedCentral® Posted Date

6-19-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

SSADHD (succinic semialdehyde dehydrogenase deficiency), succinic semialdehyde dehydrogenase, GABA catabolism, ALDH5A1, GHB (4-hydroxybutyric acid), 2-pyrrolidinone, GABA-T (GABA transaminase)

Abstract

Genomic sequencing offers an untargeted, data-driven approach to genetic diagnosis; however, variants of uncertain significance often hinder the diagnostic process. The discovery of rare genomic variants without previously known functional evidence of pathogenicity often results in variants being overlooked as potentially causative, particularly in individuals with undifferentiated phenotypes. Consequently, many neurometabolic conditions, including those in the GABA (gamma-aminobutyric acid) catabolism pathway, are underdiagnosed. Succinic semialdehyde dehydrogenase deficiency (SSADHD, OMIM #271980) is a neurometabolic disorder in the GABA catabolism pathway. The disorder is due to bi-allelic pathogenic variants in

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