Response to Stove and colleagues concerning newborn screening of succinic semialdehyde dehydrogenase (SSADH) deficiency in dried blood spots

2013 ◽  
Vol 110 (1-2) ◽  
pp. 196 ◽  
Author(s):  
Sabrina Forni ◽  
Phillip L. Pearl ◽  
K. Michael Gibson ◽  
Yuezhou Yu ◽  
Lawrence Sweetman
Keyword(s):  
Newborn Screening ◽  
Dried Blood Spots ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Blood Spots ◽  
Semialdehyde Dehydrogenase ◽  
Ssadh Deficiency

scholarly journals Novel biomarkers and age-related metabolite correlations in plasma and dried blood spots from patients with succinic semialdehyde dehydrogenase deficiency

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Trevor Kirby ◽  
Dana C. Walters ◽  
Xutong Shi ◽  
Coleman Turgeon ◽  
Piero Rinaldo ◽  
...  
Keyword(s):  
Dehydrogenase Deficiency ◽  
Dried Blood Spots ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Blood Spots ◽  
Semialdehyde Dehydrogenase ◽  
Age Related ◽  
Age Dependent ◽  
Succinic Semialdehyde Dehydrogenase Deficiency ◽  
Novel Biomarkers

Abstract Background Previous work has identified age-related negative correlations for γ-hydroxybutyric acid (GHB) and γ-aminobutyric acid (GABA) in plasma of patients with succinic semialdehyde dehydrogenase deficiency (SSADHD). Using plasma and dried blood spots (DBS) collected in an ongoing natural history study, we tested the hypothesis that other biomarkers would follow a similar age-related negative correlation as seen for GHB/GABA. Samples (mixed sex) included: patients (n = 21 unique samples, 1–39.5 yrs) and parallel controls (n = 9 unique samples, 8.4–34.8 yrs). Archival control data (DBS only; n = 171, 0.5–39.9 yrs) was also included. Results Metabolites assessed included amino acids (plasma, DBS) and acylcarnitines, creatine, creatinine, and guanidinoacetate (DBS only). Age-related negative correlations for glycine (plasma, DBS) and sarcosine (N-methylglycine, plasma) were detected, accompanied by elevated proline and decreased levels of succinylacetone, argininosuccinate, formaminoglutamate, and creatinine. Significantly low acylcarnitines were detected in patients across all chain lengths (short-, medium- and long-chain). Significant age-dependent positive correlations for selected acylcarnitines (C6-, C12DC(dicarboxylic)-, C16-, C16:1-, C18:1-, C18:2OH-carnitines) were detected in patients and absent in controls. Receiver operating characteristic (ROC) curves for all binary comparisons revealed argininosuccinate and succinylacetone to be the most discriminating biomarkers (area > 0.92). Conclusions Age-dependent acylcarnitine correlations may represent metabolic compensation responsive to age-related changes in GHB and GABA. Our study highlights novel biomarkers in SSADHD and expands the metabolic pathophysiology of this rare disorder of GABA metabolism.

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.

scholarly journals Polysomnographic Abnormalities in Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

SLEEP ◽  
2009 ◽  
Vol 32 (12) ◽  
pp. 1645-1648 ◽  
Author(s):  
Phillip L. Pearl ◽  
Sadat Shamim ◽  
William H. Theodore ◽  
K. Michael Gibson ◽  
Katherine Forester ◽  
...  
Keyword(s):  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Ssadh Deficiency

scholarly journals OCD symptoms in succinic semialdehyde dehydrogenase (SSADH) deficiency: a case report

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sachin Phakey ◽  
Thomas Rego ◽  
Frank Gaillard ◽  
Julie Panetta ◽  
Andrew Evans ◽  
...  
Keyword(s):  
Case Report ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Ssadh Deficiency

Mutation analysis and prenatal diagnosis in a Chinese family with succinic semialdehyde dehydrogenase and a systematic review of the literature of reported ALDH5A1 mutations

2016 ◽  
Vol 44 (4) ◽  
Author(s):  
Ning Liu ◽  
Xiang-dong Kong ◽  
Quan-cheng Kan ◽  
Hui-rong Shi ◽  
Qing-hua Wu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Prenatal Diagnosis ◽  
Genetic Analysis ◽  
Aminobutyric Acid ◽  
Chinese Family ◽  
Succinic Semialdehyde ◽  
Review Of The Literature ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Ssadh Deficiency

AbstractSuccinic semialdehyde dehydrogenase (SSADH) deficiency is a neurometabolic disease in which the degradation of γ-aminobutyric acid (GABA) is impaired. The purpose of this study was to report two novelGenetic analysis ofTwo novel

Speech Motor Function and Auditory Perception in Succinic Semialdehyde Dehydrogenase Deficiency: Toward Pre–Supplementary Motor Area (SMA) and SMA-Proper Dysfunctions

2021 ◽  
pp. 088307382110012
Author(s):  
Zohreh Ziatabar Ahmadi ◽  
Melissa L. DiBacco ◽  
Phillip L. Pearl
Keyword(s):  
Auditory Perception ◽  
Supplementary Motor Area ◽  
Motor Area ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Motor Functions ◽  
Semialdehyde Dehydrogenase ◽  
Magnetic Resonance Imaging Mri ◽  
Speech Motor ◽  
Ssadh Deficiency

This study reviews the fundamental roles of pre–supplementary motor area (SMA) and SMA-proper responsible for speech-motor functions and auditory perception in succinic semialdehyde dehydrogenase (SSADH) deficiency. We comprehensively searched the databases of PubMed, Google Scholar, and the electronic journals Springer, PreQuest, and Science Direct associated with keywords SSADHD, SMA, auditory perception, speech, and motor with AND operator. Transcranial magnetic stimulation emerged for assessing excitability/inhibitory M1 functions, but its role in pre-SMA and SMA proper dysfunction remains unknown. There was a lack of data on resting-state and task-based functional magnetic resonance imaging (MRI), with a focus on passive and active tasks for both speech and music, in terms of analysis of SMA-related cortex and its connections. Children with SSADH deficiency likely experience a dysfunction in connectivity between SMA portions with cortical and subcortical areas contributing to disabilities in speech-motor functions and auditory perception. Early diagnosis of auditory-motor disabilities in children with SSADH deficiency by neuroimaging techniques invites opportunities for utilizing sensory-motor integration as future interventional strategies.

Assessing Prevalence and Carrier Frequency of Succinic Semialdehyde Dehydrogenase Deficiency

2021 ◽  
Vol 36 (13-14) ◽  
pp. 1218-1222
Author(s):  
Kirt Martin ◽  
Alice McConnell ◽  
Sarah H. Elsea
Keyword(s):  
Carrier Frequency ◽  
Succinic Semialdehyde ◽  
Loss Of Function ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Asian Populations ◽  
Pathogenic Variants ◽  
Semialdehyde Dehydrogenase ◽  
Succinic Semialdehyde Dehydrogenase Deficiency ◽  
Variant Analysis ◽  
Ssadh Deficiency

Pathogenic variants in ALDH5A1 cause succinic semialdehyde dehydrogenase (SSADH) deficiency, with >180 cases reported worldwide. However, a nonspecific neurologic presentation and inconsistent variant nomenclature have limited diagnoses. In this study, pathogenic variants in ALDH5A1 were curated and variant prevalence assessed in the Genome Aggregation Database (gnomAD) to determine a minimum carrier frequency and to estimate disease prevalence. Stringent population variant analysis, including 98 reported disease-associated ALDH5A1 variants, indicates a pan-ethnic carrier frequency of ∼1/340, supporting a prevalence of SSADH deficiency of ∼1/460 000 worldwide, with highest carrier frequencies observed in East Asian and South Asian populations. Because heterozygous loss of function alleles are rare in gnomAD and >60% of reported disease-causing variants were missense changes that were not present in gnomAD, the pan-ethnic carrier frequency for SSADH deficiency is likely not fully represented in this study. Additional analyses to investigate the potential impact of more common ALDH5A1 variants with reduced but not deficient enzyme activity, including analysis in diverse populations, are needed to fully assess the prevalence of this ultra-rare disease.

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