scholarly journals Epilepsy in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

2011 ◽  
Vol 33 (9) ◽  
pp. 796-805 ◽  
Author(s):  
Phillip L. Pearl ◽  
Lovy Shukla ◽  
William H. Theodore ◽  
Cornelis Jakobs ◽  
K. Michael Gibson
Keyword(s):  
Dehydrogenase Deficiency ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Gaba Metabolism ◽  
Semialdehyde Dehydrogenase ◽  
Succinic Semialdehyde Dehydrogenase Deficiency

scholarly journals Development of a Quality-of-Life Survey for Patients With Succinic Semialdehyde Dehydrogenase Deficiency, a Rare Disorder of GABA Metabolism

2021 ◽  
pp. 088307382110283
Author(s):  
Mousumi Bose ◽  
Jean-Baptiste Roullet ◽  
K. Michael Gibson ◽  
William B. Rizzo ◽  
Hana M. Mansur ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Family Caregivers ◽  
Dehydrogenase Deficiency ◽  
Rare Disorder ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Gaba Metabolism ◽  
Semialdehyde Dehydrogenase ◽  
Succinic Semialdehyde Dehydrogenase Deficiency

Succinic semialdehyde dehydrogenase deficiency (SSADHD), a rare disorder of GABA metabolism, presents with significant neurodevelopmental morbidity. Although there is a growing interest in the concept of quality of life through patient reports as a meaningful outcome in rare disease clinical trials, little is known about the overall impact of SSADHD from the patient/family perspective. The purpose of this study was to determine issues related to quality of life and patient/family experience through a focus group discussion with family caregivers of patients with SSADHD. The discussion included the input of 5 family caregivers, and highlighted concerns related to physical function, cognitive and intellectual function, psychological and behavioral function, social function, and family impact. These themes represent appropriate starting points in the development of a quality-of-life survey that may serve as a meaningful clinical tool in future studies of SSADHD.

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.

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