Dataset Information

Clinical, biochemical and metabolic characterization of patients with short-chain enoyl-CoA hydratase(ECHS1) deficiency: two case reports and the review of the literature.

ABSTRACT: BACKGROUND:Short-chain enoyl-CoA hydratase (SCEH or ECHS1) deficiency is a rare congenital metabolic disorder caused by biallelic mutations in the ECHS gene. Clinical phenotype includes severe developmental delay, regression, dystonia, seizures, elevated lactate, and brain MRI abnormalities consistent with Leigh syndrome (LS). SCEH is most notably involved in valine catabolism. There is no effective treatment for the disease, patients may respond to dietary restriction of valine and supplementation of N-acetylcysteine . CASE PRESENTATION:We describe two patients who presented in infancy or early childhood with SCEH deficiency. Both patients were shown to harbor heterozygous or homozygous variants in the ECHS1 gene, and developmental retardation or regression as the onset manifestation. Brain MRI showed abnormal signals of bilateral pallidus. Urine metabolic examination showed increased levels of 2,3-dihydroxy-2-methylbutyric acid and S-(2-carboxypropyl) cysteamine S-(2-carboxypropoxypropyl) cysteamine (SCPCM). A valine restricted diet and combined of N-acetylcysteine supplementation were utilized in the two patients. CONCLUSIONS:In clinical practice, The elevated urinary 2,3-dihydroxy-2-methylbutyrate, S-(2-carboxypropyl) cysteine, S-(2-carboxypropyl) cysteine and N-acetyl-S-(2-carboxypropyl) cysteine levels might be clues for diagnosis of SCEH deficiency which can be confirmed throughGenetic sequencing of ECHS1 gene. Early cocktail therapy, valine restrictied diet and N-acetylcysteine supplementation could improve the prognosis of patients.

SUBMITTER: Yang H

PROVIDER: S-EPMC6996175 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Clinical, biochemical and metabolic characterization of patients with short-chain enoyl-CoA hydratase(ECHS1) deficiency: two case reports and the review of the literature.

Yang Hua H Yu Dan D

BMC pediatrics 20200203 1

<h4>Background</h4>Short-chain enoyl-CoA hydratase (SCEH or ECHS1) deficiency is a rare congenital metabolic disorder caused by biallelic mutations in the ECHS gene. Clinical phenotype includes severe developmental delay, regression, dystonia, seizures, elevated lactate, and brain MRI abnormalities consistent with Leigh syndrome (LS). SCEH is most notably involved in valine catabolism. There is no effective treatment for the disease, patients may respond to dietary restriction of valine and supp ...[more]

PMID: 32013919

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Project description:BackgroundLarge-scale "omics" datasets have not been leveraged and integrated with functional analyses to discover potential drivers of cardiomyopathy. This study addresses the knowledge gap.MethodsWe coupled RNA sequence (RNA-Seq) variant detection and transcriptome profiling with pathway analysis to model drug refractory dilated cardiomyopathy (drDCM) using the BaseSpace sequencing hub and Ingenuity Pathway Analysis. We used RNA-Seq case-control datasets (n = 6 cases, n = 4 controls), exome sequence familial DCM datasets (n = 3 Italians, n = 5 Italians, n = 5 Chinese), and controls from the HapMap project (n = 5 Caucasians, and n = 5 Asians) for disease modeling and putative mutation discovery. Variant replication datasets: n = 128 cases and n = 15 controls. Source of datasets: NCBI Sequence Read Archive.StatisticsPairwise differential expression analyses to determine differentially expressed genes and t-tests to calculate p-values. We adjusted for false discovery rates and reported q-values. We used chi-square tests to assess independence among variables, the Fisher's Exact Tests and overlap p-values for the pathways and p-scores to rank network.ResultsData revealed that ECHS1(enoyl-CoA hydratase, short chain 1(log2(foldchange) = 1.63329) hosts a mirtron, MIR3944 expressed in drDCM (FPKM = 5.2857) and not in controls (FPKM = 0). Has-miR3944-3p is a putative target of BAG1 (BCL2 associated athanogene 1(log2(foldchange) = 1.31978) and has-miR3944-5p of ITGAV (integrin subunit alpha V(log2(foldchange) = 1.46107) and RHOD (ras homolog family member D(log2(foldchange) = 1.28851). There is an association between ECHS1:11 V/A(rs10466126) and drDCM (p = 0.02496). The interaction (p = 2.82E-07) between ECHS1:75 T/I(rs1049951) and ECHS1:rs10466126 is associated with drDCM (p < 2.2e-16). ECHS1:rs10466126 and ECHS1:rs1049951 are in linkage disequilibrium (D' = 1). The interaction (p = 7.84E-08) between ECHS1:rs1049951 and the novel ECHS1:c.41insT variant is associated with drDCM (p < 2.2e-16). The interaction (p = 0.001096) between DBT (Dihydrolipoamide branched chain transacylase E2):384G/S(rs12021720) and ECHS1:rs10466126 is associated with drDCM (p < 2.2e-16). At the mRNA level, there is an association between ECHS1 (log2(foldchange) = 1.63329; q = 0.013927) and DBT (log2(foldchange) = 0.955072; q = 0.0368792) with drDCM. ECHS1 is involved in valine (-log (p = 3.39E00)), isoleucine degradation (p = 0.00457), fatty acid β-oxidation (-log(p) = 2.83E00), and drug metabolism:cytochrome P450 (z-score = 2.07985196) pathways. The mitochondria (-log(p) = 8.73E00), oxidative phosphorylation (-log(p) = 5.35E00) and TCA-cycle II (-log(p) = 2.70E00) are dysfunctional.ConclusionsWe introduce an integrative data strategy that considers the interplay between the DNA, mRNA, and associated pathways, which represents a possible diagnostic, prognostic, biomarker, and personalized treatment discovery approach in genomically heterogeneous diseases.

Dataset Information

Clinical, biochemical and metabolic characterization of patients with short-chain enoyl-CoA hydratase(ECHS1) deficiency: two case reports and the review of the literature.

Publications

Clinical, biochemical and metabolic characterization of patients with short-chain enoyl-CoA hydratase(ECHS1) deficiency: two case reports and the review of the literature.

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