Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mitochondrial HMG-CoA synthase deficiency; HMGCS2D; OMIM#605911) is a rare autosomal recessive metabolic disorder caused by mutations in the HMGCS2 gene (OMIM*600234). Here, HMGCS2 is linked to 3-hydroxy-3-methylglutaryl-CoA synthase deficiency.