Combined malonic, methylmalonic and ethylmalonic acid semialdehyde dehydrogenase deficiencies: An inborn error of ?-alanine,l-valine andl-alloisoleucine metabolism?

1993 ◽  
Vol 16 (3) ◽  
pp. 563-567 ◽  
Author(s):  
K. M. Gibson ◽  
C. F. Lee ◽  
M. J. Bennett ◽  
B. Holmes ◽  
W. L. Nyhan
Keyword(s):  
Inborn Error ◽  
Ethylmalonic Acid ◽  
Semialdehyde Dehydrogenase ◽  
Acid Semialdehyde

scholarly journals Identification and Validation of Aspartic Acid Semialdehyde Dehydrogenase as a New Anti-Mycobacterium Tuberculosis Target

2015 ◽  
Vol 16 (10) ◽  
pp. 23572-23586 ◽  
Author(s):  
Jianzhou Meng ◽  
Yanhui Yang ◽  
Chunling Xiao ◽  
Yan Guan ◽  
Xueqin Hao ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Aspartic Acid ◽  
Semialdehyde Dehydrogenase ◽  
Acid Semialdehyde

Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism

1983 ◽  
Vol 133 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Kenneth M. Gibson ◽  
Lawrence Sweetman ◽  
William L. Nyhan ◽  
Cornells Jakobs ◽  
Dietz Rating ◽  
...  
Keyword(s):  
Inborn Error ◽  
Acid Metabolism ◽  
Dehydrogenase Deficiency ◽  
Aminobutyric Acid ◽  
Succinic Semialdehyde ◽  
Gamma Aminobutyric Acid ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Succinic Semialdehyde Dehydrogenase Deficiency

scholarly journals First patient in Serbia with biochemically and genetically diagnosed pyridoxine-dependent epilepsy

2017 ◽  
Vol 74 (6) ◽  
pp. 594-597
Author(s):  
Milos Jesic ◽  
Maja Jesic ◽  
Svetlana Buljugic ◽  
Aleksandra Zivanovic
Keyword(s):  
Cerebrospinal Fluid ◽  
Inborn Error ◽  
Autosomal Recessive ◽  
Degradation Pathway ◽  
Drug Resistant ◽  
Gene Diagnosis ◽  
Genetical Analysis ◽  
Semialdehyde Dehydrogenase ◽  
Lysine Degradation ◽  
Reliable Marker

Introduction. Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive inborn error of metabolism present with early-onset seizures resistant to common anticonvulsants. PDE has been shown to be caused by a defect of a ?-aminoadipic semialdehyde dehydrogenase (also known as ALDH7A1 or antiquitin) in the cerebral lysine degradation pathway. Its deficiency results in accumulation of ?-aminoadipic semialdehyde (?-AASA), piperideine -6-carboxylate and pipecolic acid, which serve as diagnostic markers in urine, plasma and cerebrospinal fluid of the disease. ?-Aminoadipic semialdehyde dehydrogenase is encoded by the ALDH7A1 or antiquitin gene and definite confirmation of diagnosis of PDE is made by genetic analysis. Case report. We present a first patient in Serbia who was diagnosed clinically, biochemically and genetically. We suspected PDE due to drug-resistant seizures in the seventh day of life when we attempted with pyridoxine. Since that time the patient has taken pyridoxine and the seizures have not recured. Our patient had markedly elevated ?- AASA in urine while on treatment with individual dosages of pyridoxine. Molecular-genetical analysis identified mutations of the ALDH7A1 (antiquitin) gene. Conclusion. ?-AASA is reliable marker to select PDF patient for molecular analysis of the ALDH7A1(antiquitin) gene. Diagnosis is confirmed by molecular- genetical analysis and pyridoxine withdrawal is no longer needed to establish the diagnosis of ?definite? PDE.

scholarly journals Succinic Semialdehyde Dehydrogenase Deficiency: Review of the Natural History Study

2021 ◽  
pp. 088307382098126
Author(s):  
Phillip L. Pearl ◽  
Melissa L. DiBacco ◽  
Christos Papadelis ◽  
Thomas Opladen ◽  
Ellen Hanson ◽  
...  
Keyword(s):  
Natural History ◽  
Psychiatric Symptoms ◽  
Epileptiform Activity ◽  
Laboratory Data ◽  
Standard Of Care ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Natural History Study ◽  
Semialdehyde Dehydrogenase ◽  
Verbal Score

Objective: The SSADHD Natural History Study was initiated in 2019 to define the natural course and identify biomarkers correlating with severity. Methods: The study is conducted by 4 institutions: BCH (US clinical), WSU (bioanalytical core), USF (biostatistical core), and Heidelberg (iNTD), with support from the family advocacy group (SSADH Association). Recruitment goals were to study 20 patients on-site at BCH, 10 with iNTD, and 25 as a standard-of care cohort. Results: At this half-way point of this longitudinal study, 28 subjects have been recruited (57% female, mean 9 years, range 18 months–40 years). Epilepsy is present in half and increases in incidence and severity, as do psychiatric symptoms, in adolescence and adulthood. The average Full Scale IQ (FSIQ) was 53 (Verbal score of 56, Non Verbal score of 49), and half scored as having ASD. Although there was no correlation between gene variant and phenotypic severity, there were extreme cases of lowest functioning in one individual and highest in another that may have genotype-phenotype correlation. The most common EEG finding was mild background slowing with rare epileptiform activity, whereas high-density EEG and magnetoencephalography showed reduction in the gamma frequency band consistent with GABAergic dysfunction. MR spectroscopy showed elevations in the GABA/NAA ratio in all regions studied with no crossover between subjects and controls. Conclusions: The SSADH Natural History Study is providing a unique opportunity to study the complex pathophysiology longitudinally and derive electrophysiologic, neuroimaging, and laboratory data for correlation and to serve as biomarkers for clinical trials and prognostic assessments in this ultra-rare inherited disorder of GABA metabolism.

scholarly journals α-Ketoglutaric Semialdehyde Dehydrogenase of Pseudomonas

1974 ◽  
Vol 249 (6) ◽  
pp. 1704-1716
Author(s):  
Peter H. Koo ◽  
Elijah Adams
Keyword(s):  
Semialdehyde Dehydrogenase

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 Magnetic Resonance Imaging (MRI) and Spectroscopy in Succinic Semialdehyde Dehydrogenase Deficiency

2021 ◽  
pp. 088307382199129
Author(s):  
Onur Afacan ◽  
Edward Yang ◽  
Alexander P. Lin ◽  
Eduardo Coello ◽  
Melissa L. DiBacco ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Mr Spectroscopy ◽  
Succinic Semialdehyde ◽  
Resonance Imaging ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Magnetic Resonance Imaging Mri ◽  
Brain Gaba ◽  
Ssadh Deficiency

Succinic semialdehyde dehydrogenase (SSADH) deficiency is an autosomal recessive disorder of γ-aminobutyric acid (GABA) degradation, resulting in elevations of brain GABA and γ-hydroxybutyric acid (GHB). Previous magnetic resonance (MR) spectroscopy studies have shown increased levels of Glx in SSADH deficiency patients. Here in this work, we measure brain GABA in a large cohort of SSADH deficiency patients using advanced MR spectroscopy techniques that allow separation of GABA from overlapping metabolite peaks. We observed significant increases in GABA concentrations in SSADH deficiency patients for all 3 brain regions that were evaluated. Although GABA levels were higher in all 3 regions, each region had different patterns in terms of GABA changes with respect to age. We also report results from structural magnetic resonance imaging (MRI) of the same cohort compared with age-matched controls. We consistently observed signal hyperintensities in globus pallidus and cerebellar dentate nucleus.

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