ArticleInternational journal of molecular sciences2018
Human Mitochondrial HMG-CoA Synthase Deficiency: Role of Enzyme Dimerization Surface and Characterization of Three New Patients.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 27 citations in OpenAlex.
- Genetic architecture of plasma metabolome in 254,825 individuals.Nature communications · 2025Article
- Ligand-Enzyme Interaction Modeling of Missense Variants Implicated in Mitochondrial HMG-CoA Synthase Deficiency.International journal of molecular sciences · 2025Article
- HMG-CoA Synthase-2 Deficiency: Neonatal Hyperammonemic Coma and Abnormal Metabolic Screening Resembling Maple Syrup Urine Disease.JIMD reports · 2025Article
- HMGCS1 variants cause rigid spine syndrome amenable to mevalonic acid treatment in an animal model.Brain : a journal of neurology · 2025Article
- Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.Biomolecules · 2025Review
- Mitochondrial HMG-CoA Synthase Deficiency in Vietnamese Patients.International journal of molecular sciences · 2025Article
- Critical sample collection delayed? Urine organic acid analysis can still save the day! A new case of HMG-CoA synthase deficiency.Molecular genetics and metabolism reports · 2024Article
- Mitochondrial 3-hydroxymethylglutaryl-CoA synthase-2 (HMGCS2) deficiency: a rare case with bicytopenia and coagulopathy.BMJ case reports · 2023Article
- Metabolic Changes Associated With Cardiomyocyte Dedifferentiation Enable Adult Mammalian Cardiac Regeneration.Circulation · 2022Article
- Hmgcs2-mediated ketogenesis modulates high-fat diet-induced hepatosteatosis.Molecular metabolism · 2022Article
- Emerging Role of Hepatic Ketogenesis in Fatty Liver Disease.Frontiers in physiology · 2022Review
- Hypoglycaemia Metabolic Gene Panel Testing.Frontiers in endocrinology · 2022Review
- Japanese patients with mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency:Experimental and therapeutic medicine · 2020Article
- Association of a novel homozygous mutation in the HMGCS2 gene with an HMGCSD in an Iranian patient.Molecular genetics & genomic medicine · 2020Article
- Article
- The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice.PloS one · 2020Article
- A Japanese case of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency who presented with severe metabolic acidosis and fatty liver without hypoglycemia.JIMD reports · 2019Article
- NovelPediatric investigation · 2019Article
- [Mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase deficiency: a case report and literature review].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2018Review
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Authors and funding
10 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mitochondrial HMG-CoA synthase deficiency or mHS deficiency, OMIM #605911) is an inborn error of metabolism that affects ketone body synthesis. Acute episodes include vomiting, lethargy, hepatomegaly, hypoglycemia and dicarboxylic aciduria. The diagnosis is difficult due to the relatively unspecific clinical and biochemical presentation, and fewer than 30 patients have been described. This work describes three new patients with mHS deficiency and two missense mutations c.334C>T (p.R112W) and c.430G>T (p.V144L) previously not reported. We developed a new method to express and measure the activity of the enzyme and in this work the study is extended to ten new missense variants including those of our patients. Enzymatic assays showed that three of the mutant proteins retained some but seven completely lacked activity. The identification of a patient homozygous for a mutation that retains 70% of enzyme activity opens the door to a new interpretation of the disease by demonstrating that a modest impairment of enzyme function can actually produce symptoms. This is also the first study employing molecular dynamics modelling of the enzyme mutations. We show that the correct maintenance of the dimerization surface is crucial for retaining the structure of the active center and therefore the activity of the enzyme.
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