HMGCS2 and hyperinsulinemic hypoglycemia, familial, 4: Homozygous variants in human HMGCS2 are well known to cause the very rare metabolic disorder HMGCS2 deficiency [24] (OMIM: 605911), which is characterized by severe hypoketotic hypoglycemia, encephalopathy, and hepatomegaly that is triggered after extended periods of fasting or after infections [28].