TH and dystonia 5: For classic DRD (Table 1), there are three known causative genes: 1) the GCH1 gene on chromosome 14q, encoding GTPCH, the rate-limiting enzyme in the biosynthetic pathway for tetrahydrobiopterin (BH4: the natural cofactor for TH, tryptophan hydroxylase [TPH], and phenylalanine hydroxylase) (Figure 1); 2) the TH gene on 11p, coding for TH, the rate-limiting enzyme in catecholamine biosynthesis; and 3) the SPR gene on 2p, encoding sepiapterin reductase (SR), an enzyme involved in the final step of BH4 synthesis17).