A case report of short-chain acyl-CoA dehydrogenase deficiency (SCADD)

Lampret, Barbka Repič; Murko, Simona; Debeljak, Maruša; Tanšek, Mojca Žerjav; Fister, Petja; Battelino, Tadej

doi:10.11613/bm.2015.029

Cited by 10 publications

(3 citation statements)

References 24 publications

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“…Both SUCLG2, encoding a succinyl-CoA ligase, and the metabolite is involved in succinyl-CoA pathways. Mutation in ACADS causes short-chain acyl-CoA dehydrogenase de ciency and methylsuccinate level was altered in this disorder 30 . The SLC13A3 encoded protein can transport succinate, which is a building block for methylsuccinoylcarnitine.…”

Section: Pleiotropic Loci and Polygenic Metabolitesmentioning

confidence: 97%

Unique genetic architecture of CSF and brain metabolites pinpoints the novel targets for the traits of human wellness

Wang

Western

Yang

et al. 2023

Preprint

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Brain metabolism perturbation can contribute to traits and diseases. We conducted the first large-scale CSF and brain genome-wide association studies, which identified 219 independent associations (59.8% novel) for 144 CSF metabolites and 36 independent associations (55.6% novel) for 34 brain metabolites. Most of the novel signals (97.7% and 70.0% in CSF and brain) were tissue specific. We also integrated MWAS-FUSION approaches with Mendelian Randomization and colocalization to identify causal metabolites for 27 brain and human wellness phenotypes and identified eight metabolites to be causal for eight traits (11 relationships). Low mannose level was causal to bipolar disorder and as dietary supplement it may provide therapeutic benefits. Low galactosylglycerol level was found causal to Parkinson’s Disease (PD). Our study expanded the knowledge of MQTL in central nervous system, provided insights into human wellness, and successfully demonstrates the utility of combined statistical approaches to inform interventions.

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Section: Pleiotropic Loci and Polygenic Metabolitesmentioning

confidence: 97%

Unique genetic architecture of CSF and brain metabolites pinpoints the novel targets for the traits of human wellness

Wang

Western

Yang

et al. 2023

Preprint

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“…autosomal recessive genetic disorder of fatty acid catabolism caused by mutations in the acylcoenzyme A dehydrogenase, C-2 to C-3 short chain (ACADS) gene (OMIM 606885) [40]. The ACADS protein catalyses the first step in the mitochondrial oxidation of fatty acids four to six carbons in length [41].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Tread carefully: A functional variant in the human NADPH oxidase 4 ( NOX4 ) is not disease causing

Nafisinia

Menezes

Gold

et al. 2018

Molecular Genetics and Metabolism

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In this study, we report a paediatric patient with a lethal phenotype of respiratory distress, failure to thrive, pancreatic insufficiency, liver dysfunction, hypertrophic cardiomyopathy, bone marrow suppression, humoral and cellular immune deficiency. To identify the genetic basis of this unusual clinical phenotype and potentially make available the option of future prenatal testing, whole exome sequencing (WES) was used followed by functional studies in a bid to confirm pathogenicity. The WES we identified a homozygous novel variant, AK298328; c.9_10insGAG; p.[Glu3dup], in NOX4 in the proband, and parental heterozygosity for the variant (confirmed by Sanger sequencing). NADPH Oxidase 4 NOX4 (OMIM 605261) encodes an enzyme that functions as the catalytic subunit of the NADPH oxidase complex. NOX4 acts as an oxygen sensor, catalysing the reduction of molecular oxygen, mainly to hydrogen peroxide (HO). However, although, our functional data including 60% reduction in NOX4 protein levels and a 75% reduction in the production of HO in patient fibroblast extracts compared to controls was initially considered to be the likely cause of the phenotype in our patient, the potential contribution of the NOX4 variant as the primary cause of the disease was clearly excluded based on following pieces of evidence. First, Sanger sequencing of other family members revealed that two of the grandparents were also homozygous for the NOX4 variant, one of who has fibromuscular dysplasia. Second, re-evaluation of more recent variant databases revealed a high allele frequency for this variant. Our case highlights the need to re-interrogate bioinformatics resources as they are constantly evolving, and is reminiscent of the short-chain acyl-CoA dehydrogenase deficiency (SCADD) story, where a functional defect in fatty acid oxidation has doubtful clinical ramifications.

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“…9 Among the acyl-coenzyme A dehydrogenase family members, SCAD is most closely bounded with flavin adenine dinucleotide. 10 Studies have shown that patients with medium-chain acyl-coenzyme A dehydrogenase deficiency can still maintain energy metabolism through the oxidation of short-chain fatty acids, which indicates that short-chain fatty acids metabolism plays an essential role in fatty acids β-oxidation. 11 Our previous research revealed that the expression of SCAD had a time-dependent increase during normal rat heart development, which was lowest in the fetal and neonatal rat hearts.…”

Section: Introductionmentioning

confidence: 99%

Short-Chain Acyl-CoA Dehydrogenase as a Therapeutic Target for Cardiac Fibrosis

Shu,

Feng,

Liu

et al. 2024

Journal of Cardiovascular Pharmacology

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Cardiac fibrosis is considered as unbalanced extracellular matrix (ECM) production and degradation, contributing to heart failure. Short-chain acyl-CoA dehydrogenase (SCAD) negatively regulates pathological cardiac hypertrophy. The purpose of this study was to investigate the possible role of SCAD in cardiac fibrosis. In-vivo experiments were performed on spontaneously hypertensive rats (SHR) and SCAD knockout mice. The cardiac tissues of hypertensive patients with cardiac fibrosis were used for measurement of SCAD expression. In-vitro experiments, with angiotensin II (Ang II), SCAD siRNA and adenovirus-SCAD (Ad-SCAD) were performed using cardiac fibroblasts (CFs). SCAD expression was significantly decreased in the left ventricles of SHR. Notably, swim training ameliorated cardiac fibrosis in SHR in association with the elevation of SCAD. The decrease in SCAD protein and mRNA expression levels in SHR CFs were in accordance with those in the left ventricular myocardium of SHR. In addition, SCAD expression was downregulated in CFs treated with Ang II in vitro, and SCAD siRNA interference induced the same changes in cardiac fibrosis as Ang II-treated CFs, while Ad-SCAD treatment significantly reduced the Ang II-induced CFs proliferation, α-SMA and collagen expression. In SHR infected with Ad-SCAD, the cardiac fibrosis of the left ventricle was significantly decreased. On the other hand, cardiac fibrosis occurred in conventional SCAD knockout mice. SCAD immunofluorescence intensity of cardiac tissue in hypertensive patients with cardiac fibrosis was lower than that of healthy subjects. All together, the current experimental outcomes indicate that SCAD has a negative regulatory effect on cardiac fibrosis and support its potential therapeutic target for suppressing cardiac fibrosis.

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A case report of short-chain acyl-CoA dehydrogenase deficiency (SCADD)

Cited by 10 publications

References 24 publications

Unique genetic architecture of CSF and brain metabolites pinpoints the novel targets for the traits of human wellness

Unique genetic architecture of CSF and brain metabolites pinpoints the novel targets for the traits of human wellness

Tread carefully: A functional variant in the human NADPH oxidase 4 ( NOX4 ) is not disease causing

Short-Chain Acyl-CoA Dehydrogenase as a Therapeutic Target for Cardiac Fibrosis

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