Japanese patients with mitochondrial 3‑hydroxy‑3‑methylglutaryl‑CoA synthase deficiency: In vitro functional analysis of five novel HMGCS2 mutations

摘要: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) deficiency is a metabolic disorder caused by mutations in the HMGCS2 gene. The present study describes identification of four cases Japan. Hepatomegaly and severe acidosis were observed all cases. Fatty liver was identified three cases, which suggested unavailability fatty acids. All patients presented with high C2/C0 ratio, suggesting that acid oxidation pathway normal during crisis. Genetic analyses revealed five rare, novel variants (p.G219E, p.M235T, p.V253A, p.S392L p.R500C) HMGCS2. To confirm their pathogenicity, eukaryotic expression system bacterial adopted successfully used to obtain affinity-purified protein measurable activity. Purified M235T, S392L R500C proteins did not retain any residual activity, whilst V253A variant showed some enzymatic Judging from transient experiment 293T cells, G219E appeared be unstable. In conclusion, indicated pathogenic affected deficiency.