2022
DOI: 10.1186/s13023-022-02468-6
|View full text |Cite
|
Sign up to set email alerts
|

Clinical improvements after treatment with a low-valine and low-fat diet in a pediatric patient with enoyl-CoA hydratase, short chain 1 (ECHS1) deficiency

Abstract: Background Enoyl-CoA hydratase short-chain 1 (ECHS1) is a key mitochondrial enzyme that is involved in valine catabolism and fatty acid beta-oxidation. Mutations in the ECHS1 gene lead to enzymatic deficiency, resulting in the accumulation of certain intermediates from the valine catabolism pathway. This disrupts the pyruvate dehydrogenase complex and the mitochondrial respiratory chain, with consequent cellular damage. Patients present with a variable age of onset and a wide spectrum of clinic… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
4
1

Citation Types

0
7
0

Year Published

2022
2022
2024
2024

Publication Types

Select...
3
2

Relationship

0
5

Authors

Journals

citations
Cited by 6 publications
(7 citation statements)
references
References 37 publications
0
7
0
Order By: Relevance
“…In ECHS1D, accumulation of reactive valine intermediates is thought to be toxic and dietary valine restriction is proposed to stabilize patient symptoms. [10][11][12][13][14] To test if dietary valine supplementation exacerbates the disease phenotype of ECHS1D mice, a custom diet containing a 3% increase in valine content was formulated and provided to breeders (Fig. 7A).…”
Section: Disease Drivers Dietary Valinementioning
confidence: 99%
See 1 more Smart Citation
“…In ECHS1D, accumulation of reactive valine intermediates is thought to be toxic and dietary valine restriction is proposed to stabilize patient symptoms. [10][11][12][13][14] To test if dietary valine supplementation exacerbates the disease phenotype of ECHS1D mice, a custom diet containing a 3% increase in valine content was formulated and provided to breeders (Fig. 7A).…”
Section: Disease Drivers Dietary Valinementioning
confidence: 99%
“…10 Based on this, dietary reduction of valine intake has been performed in a few patients with variable success in symptom management. [10][11][12][13][14] It is hypothesized that accumulation of toxic valine intermediates within mitochondria disrupt normal function. 15 Measures of mitochondrial function in patient fibroblasts showed decreased activity of pyruvate dehydrogenase complex (PDC) and oxidative phosphorylation (OxPhos) complexes, but these findings are variable.…”
Section: Introductionmentioning
confidence: 99%
“…In addition, medical foods resulted in iatrogenic amino acid deficiencies that were associated with adverse growth outcomes 13,20 . Therefore, there is a need for new therapeutic options such as pharmacological substrate reduction that may further improve outcome in PA. A low valine diet appeared beneficial in patients with ECHS1 and HIBCH deficiency, however, additional studies are needed to fully understand clinical outcomes 21–26 …”
Section: Introductionmentioning
confidence: 99%
“…13,20 Therefore, there is a need for new therapeutic options such as pharmacological substrate reduction that may further improve outcome in PA. A low valine diet appeared beneficial in patients with ECHS1 and HIBCH deficiency, however, additional studies are needed to fully understand clinical outcomes. [21][22][23][24][25][26] The degradation of all three branched-chain amino acids (BCAA; valine, leucine and isoleucine) starts with transamination and oxidative decarboxylation by shared enzymes (Figure S1). 27,28 The third step of BCAA degradation is catalyzed by three specific acyl-CoA dehydrogenases (ACADs).…”
Section: Introductionmentioning
confidence: 99%
“…In addition, medical foods resulted in iatrogenic amino acid deficiencies that were associated with adverse growth outcomes (Fraser and Venditti 2016; Manoli et al 2016). Therefore, there is a need for new therapeutic options such as pharmacological substrate reduction that may further improve outcome in PA. A low valine diet appeared beneficial in patients with ECHS1 and HIBCH deficiency, however, additional studies are needed to fully understand clinical outcomes (Soler-Alfonso et al 2015; Shayota et al 2019; Xu et al 2019; Abdenur et al 2020; Sato-Shirai et al 2021; Pata et al 2022). The degradation of all three branched-chain amino acids (BCAA; valine, leucine and isoleucine) starts with transamination and oxidative decarboxylation by shared enzymes ( Fig.…”
Section: Introductionmentioning
confidence: 99%