While sepiapterin can be in parts transformed into BH2 by CR1 and CR4, it has been proposed that the low activity of DHFR in the brain prevents the production of BH4 (Bonafé et al., 2001), which would explain the observed BH2 accumulation in CSF of SRD patients. The gene discussed is DHFR; the disease is dopa-responsive dystonia due to sepiapterin reductase deficiency.