A natural history evaluation in a mouse model of PKU demonstrated a profound decrease in tyrosine hydroxylase (TH) immunoreactivity in several brain regions, beginning at 4weeks of age.
Inherited defects that reduce the concentration of BH4, therefore, in general, lead to phenylketonuria and to deficiencies of dopamine and serotonin, as tyrosine hydroxylase and tryptophan hydroxylase are the rate-limiting enzymes required for the synthesis of these neurotransmitters.