Phenylketonuria

"PKU" redirects here. For other uses, see PKU (disambiguation).

Phenylketonuria
Other namesPhenylalanine hydroxylase deficiency, PAH deficiency, Følling disease[1]
Phenylalanine
SpecialtyMedical genetics, pediatrics, dietetics
SymptomsWithout treatment intellectual disability, seizures, behavioral problems, mental disorders, musty odor[1]
Usual onsetAt birth[2]
TypesClassic, variant[1]
CausesGenetic (autosomal recessive)[1]
Diagnostic methodNewborn screening programs in many countries[3]
TreatmentDiet low in foods that contain phenylalanine; special supplements[2]
MedicationSapropterin dihydrochloride,[2] pegvaliase[4]
PrognosisNormal health with treatment[5]
Frequency~1 in 12,000 newborns[6]

Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine.[3] Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders.[1][7] It may also result in a musty smell and lighter skin.[1] A baby born to a mother who has poorly treated PKU may have heart problems, a small head, and low birth weight.[1]

Phenylketonuria is an inherited genetic disorder. It is caused by mutations in the PAH gene, which can result in inefficient or nonfunctional phenylalanine hydroxylase, an enzyme responsible for the metabolism of excess phenylalanine. This results in the buildup of dietary phenylalanine to potentially toxic levels. It is autosomal recessive, meaning that both copies of the gene must be mutated for the condition to develop. There are two main types, classic PKU and variant PKU, depending on whether any enzyme function remains. Those with one copy of a mutated gene typically do not have symptoms.[1] Many countries have newborn screening programs for the disease.[3]

Treatment is with a diet that (1) is low in foods that contain phenylalanine, and which (2) includes special supplements. Babies should use a special formula with a small amount of breast milk. The diet should begin as soon as possible after birth and be continued for life.[2] People who are diagnosed early and maintain a strict diet can have normal health and a normal life span. Effectiveness is monitored through periodic blood tests.[5] The medication sapropterin dihydrochloride may be useful in some.[2]

Phenylketonuria affects about 1 in 12,000 babies.[6] Males and females are affected equally.[8] The disease was discovered in 1934 by Ivar Asbjørn Følling, with the importance of diet determined in 1935.[9] As of 2023, genetic therapies that aim to directly restore liver PAH activity are a promising and active research field.[10]

  1. ^ a b c d e f g h "phenylketonuria". Genetics Home Reference. September 8, 2016. Archived from the original on 27 July 2016. Retrieved 12 September 2016.
  2. ^ a b c d e "What are common treatments for phenylketonuria (PKU)?". NICHD. 2013-08-23. Archived from the original on 5 October 2016. Retrieved 12 September 2016.
  3. ^ a b c Al Hafid N, Christodoulou J (October 2015). "Phenylketonuria: a review of current and future treatments". Translational Pediatrics. 4 (4): 304–17. doi:10.3978/j.issn.2224-4336.2015.10.07. PMC 4728993. PMID 26835392.
  4. ^ Cite error: The named reference FDA2018Sub was invoked but never defined (see the help page).
  5. ^ a b "National Institutes of Health Consensus Development Conference Statement Phenylketonuria: Screening and Management". NICHD. October 16–18, 2000. Archived from the original on 5 October 2016. Retrieved 12 September 2016.
  6. ^ a b Bernstein LE, Rohr F, Helm JR (2015). Nutrition Management of Inherited Metabolic Diseases: Lessons from Metabolic University. Springer. p. 91. ISBN 9783319146218. Archived from the original on 2017-09-11.
  7. ^ Cannon Homaei S, Barone H, Kleppe R, Betari N, Reif A, Haavik J (November 2021). "ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications". Neuroscience and Biobehavioral Reviews. 132: 838–856. doi:10.1016/j.neubiorev.2021.11.012. PMID 34774900. S2CID 243983688.
  8. ^ Marcdante K, Kliegman RM (2014). Nelson Essentials of Pediatrics (7 ed.). Elsevier Health Sciences. p. 150. ISBN 9780323226981. Archived from the original on 2017-09-11.
  9. ^ Kalter H (2010). Teratology in the Twentieth Century Plus Ten. Springer Science & Business Media. pp. 89–92. ISBN 9789048188208. Archived from the original on 2017-09-11.
  10. ^ Martinez M, Harding CO, Schwank G, Thöny B (January 2024). "State-of-the-art 2023 on gene therapy for phenylketonuria". Journal of Inherited Metabolic Disease. 47 (1): 80–92. doi:10.1002/jimd.12651. ISSN 0141-8955. PMC 10764640. PMID 37401651.