Current state of the treatment landscape of phenylketonuria

Abstract 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 h...

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Bibliographic Details
Main Authors: Ine Nulmans, Sien Lequeue, Liesbeth Desmet, Jessie Neuckermans, Joery De Kock
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Orphanet Journal of Rare Diseases
Online Access:https://doi.org/10.1186/s13023-025-03840-y
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Summary:Abstract 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.
ISSN:1750-1172