Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mHS deficiency) is a rare autosomal recessive inborn error of ketogenesis caused by a mutation in the <i>HMGCS2</i> gene, which is characterized by non-(hypo)-ketotic hypoglycemia, lethargy, and hepatomegaly during acute infection and/or prolonged fasting. This evidence concerns the gene HMGCS2 and 3-hydroxy-3-methylglutaryl-CoA synthase deficiency.