In patients with phenylketonuria (PKU) blood phenylalanine concentration during childhood is
the major determinant of cognitive outcome. Thanks to newborn screening and early dietary
therapy individuals with PKU no longer experience intellectual disability. Nevertheless some
do not achieve their full potential. The establishment of uniform guidelines and improved
management for PKU can lead to optimal outcomes in this metabolic disorder. Since in 1999 it
has been shown that some patients with PKU respond to the administration of tetrahydrobiopterin
(BH4 sapropterin dihydrochloride) by lowering blood phenylalanine concentrations that these
patients can be treated with sapropterin dihydrochloride. Enzyme substitution therapy with
phenylalanine ammonia lyase (PAL) is a promising new option along with diet and sapropterin
to reduce Phe levels and improve the clinical outcome of subjects with PKU. Gene therapy is
another new approach which remains to be evaluated in upcoming studies. It has been also shown
that patient's genotype determines the phenotype and helps in predicting BH4 responsiveness. In
the 4th edition of this textbook past present and future efforts related to PKU and BH4
deficiencies are discussed. The reviews and scientific contributions in this book provide
professionals the patients and their families to understand PKU within a biochemical
neurological and psychological context.
