Current state of the treatment landscape of phenylketonuria.

BACKGROUND

Phenylketonuria (PKU) is an inborn error of amino acid metabolism caused by a deficiency of the L-phenylalanine-4-hydroxylase enzyme or its cofactor tetrahydrobiopterin (BH4) resulting in increased levels of phenylalanine (Phe) in blood and cerebrospinal fluid. Symptoms include hypopigmentation, a musty, mouse-like smell and various neurological complications.

MAIN TEXT: Treatment options include (i) dietary restriction of Phe with supplementation of other amino acids and micronutrients through medical mixtures, (ii) daily dosing of large neutral amino acids, (iii) synthetic forms of BH4 and (iv) bacterial phenylalanine ammonia lyase enzymes. The primary goal of treatment is to lower blood Phe levels and improve quality of life. However, treatment is very demanding for patients as well as their families, and not all treatment options are applicable to every patient.

CONCLUSION

This review gives a state-of-the-art overview of current treatment options for all PKU patients and additionally speculates on future therapeutic approaches.