Bi-allelic Mutations in ALDH5A1 is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability

Gene ◽  
2020 ◽  
pp. 144918
Author(s):  
Mahshid Fattahi ◽  
Ata Bushehri ◽  
Afagh Alavi ◽  
Vahid Asghariazar ◽  
Ahoura Nozari ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Dehydrogenase Deficiency ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Severe Intellectual Disability ◽  
Succinic Semialdehyde Dehydrogenase Deficiency

scholarly journals Postmortem Analyses in a Patient With Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD): II. Histological, Lipid, and Gene Expression Outcomes in Regional Brain Tissue

2021 ◽  
pp. 088307382098774
Author(s):  
Dana C. Walters ◽  
Regan Lawrence ◽  
Trevor Kirby ◽  
Jared T. Ahrendsen ◽  
Matthew P. Anderson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dehydrogenase Deficiency ◽  
Metabotropic Glutamate Receptor ◽  
Total Phospholipid ◽  
Null Mouse ◽  
Succinic Semialdehyde ◽  
Long Term Effects ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Succinic Semialdehyde Dehydrogenase Deficiency

This study has extended previous metabolic measures in postmortem tissues (frontal and parietal lobes, pons, cerebellum, hippocampus, and cerebral cortex) obtained from a 37-year-old male patient with succinic semialdehyde dehydrogenase deficiency (SSADHD) who expired from SUDEP (sudden unexplained death in epilepsy). Histopathologic characterization of fixed cortex and hippocampus revealed mild to moderate astrogliosis, especially in white matter. Analysis of total phospholipid mass in all sections of the patient revealed a 61% increase in cortex and 51% decrease in hippocampus as compared to (n = 2-4) approximately age-matched controls. Examination of mass and molar composition of major phospholipid classes showed decreases in phospholipids enriched in myelin, such as phosphatidylserine, sphingomyelin, and ethanolamine plasmalogen. Evaluation of gene expression (RT2 Profiler PCR Arrays, GABA, glutamate; Qiagen) revealed dysregulation in 14/15 GABAA receptor subunits in cerebellum, parietal, and frontal lobes with the most significant downregulation in ∊, θ, ρ1, and ρ2 subunits (7.7-9.9-fold). GABAB receptor subunits were largely unaffected, as were ionotropic glutamate receptors. The metabotropic glutamate receptor 6 was consistently downregulated (maximum 5.9-fold) as was the neurotransmitter transporter (GABA), member 13 (maximum 7.3-fold). For other genes, consistent dysregulation was seen for interleukin 1β (maximum downregulation 9.9-fold) and synuclein α (maximal upregulation 6.5-fold). Our data provide unique insight into SSADHD brain function, confirming astrogliosis and lipid abnormalities previously observed in the null mouse model while highlighting long-term effects on GABAergic/glutamatergic gene expression in this disorder.

scholarly journals Metabolic stroke: A novel presentation in a child with succinic semialdehyde dehydrogenase deficiency

2019 ◽  
Vol 0 (0) ◽  
pp. 0
Author(s):  
Gautham Arunachal ◽  
Sangeetha Yoganathan ◽  
Lisa Kratz ◽  
Mugil Varman ◽  
Maya Thomas ◽  
...  
Keyword(s):  
Dehydrogenase Deficiency ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Succinic Semialdehyde Dehydrogenase Deficiency ◽  
Metabolic Stroke

Succinic Semialdehyde Dehydrogenase Deficiency Presenting as Autism Spectrum Disorder

2016 ◽  
Vol 83 (9) ◽  
pp. 1036-1037 ◽  
Author(s):  
Maria Gogou ◽  
Martha Spilioti ◽  
Despoina Tramma ◽  
Efimia Papadopoulou-Alataki ◽  
Athanasios Evangeliou
Keyword(s):  
Autism Spectrum Disorder ◽  
Dehydrogenase Deficiency ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Succinic Semialdehyde Dehydrogenase Deficiency

scholarly journals Biomarkers in a Taurine Trial for Succinic Semialdehyde Dehydrogenase Deficiency

2015 ◽  
pp. 81-87 ◽  
Author(s):  
John M. Schreiber ◽  
Phillip L. Pearl ◽  
Irene Dustin ◽  
Edythe Wiggs ◽  
Emily Barrios ◽  
...  
Keyword(s):  
Dehydrogenase Deficiency ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Succinic Semialdehyde Dehydrogenase Deficiency
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