In addition, severe HHcy is often triggered by congenital deficiency of cystathionine β-synthase (CBS) or 5,10-methylenetetrahydrofolate reductase (MTHFR) [15], and the most frequent cause is a rare autosomal recessive mutation in the CBS gene. The gene discussed is CBS; the disease is hyperinsulinemic hypoglycemia, familial, 4.