The enzymes used for BH4 biosynthesis are guanosine triphosphate cyclohydrolase 1 (GTPCH, EC3.5.4.16), 6‐pyruvoyltetrahydropterin synthase (6‐PTPS, EC 4.2.3.12), and sepiapterin reductase (SR, EC 4.1.1.17) causing guanosine triphosphate cyclohydrolase (GTPCH) deficiency (OMIM 233910), 6‐pyruvoyl tetrahydrobiopterin synthase (PTPS) deficiency (OMIM 261640) and sepiapterin reductase (SPR) deficiency (OMIM 612716), respectively. The gene discussed is SPR; the disease is hyperinsulinemic hypoglycemia, familial, 4.