Human Mitochondrial HMG-CoA Synthase Deficiency: Role of Enzyme Dimerization Surface and Characterization of Three New Patients.

摘要: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mitochondrial HMG-CoA 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 difficult due to the relatively unspecific clinical biochemical presentation, fewer than 30 patients have been described. This work describes three new with two missense mutations c.334C>T (p.R112W) c.430G>T (p.V144L) previously not reported. We developed a method express measure activity enzyme in this study extended ten variants including those our patients. Enzymatic assays showed mutant proteins retained some but seven completely lacked activity. identification patient homozygous for mutation retains 70% opens door interpretation disease by demonstrating modest impairment function can actually produce symptoms. also first employing molecular dynamics modelling mutations. show correct maintenance dimerization surface crucial retaining structure active center therefore enzyme.