[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Phenylketonuria (PKU) [Conditions](https://durgical.com/en/conditions/) · [Metabolism: amino acids and the urea cycle](https://durgical.com/en/conditions/) # Phenylketonuria (PKU) In phenylketonuria the body cannot process the phenylalanine in protein; untreated from birth, it damages the brain. Updated 2026-11-01 ## Structures involved Tap one to see what it is and open it in 3D. - [White matter](https://durgical.com/en/anatomy/white-matter-of-telencephalon/) - [Liver](https://durgical.com/en/anatomy/liver/) - [Frontal lobe](https://durgical.com/en/anatomy/superior-frontal-gyrus/) - [Skin](https://durgical.com/en/anatomy/skin/) ## In biochemistry - [Phenylalanine and tyrosine metabolism: Step 1 · Phenylalanine hydroxylase (PAH)](https://durgical.com/en/biochemistry/pathways/phenylalanine-and-tyrosine-metabolism/#paso-1) - [Phenylalanine](https://durgical.com/en/biochemistry/molecules/phenylalanine/) - [Tetrahydrobiopterin (BH4)](https://durgical.com/en/biochemistry/molecules/tetrahydrobiopterin/) - [Phenylalanine hydroxylase (PAH)](https://durgical.com/en/biochemistry/enzymes/phenylalanine-hydroxylase/) - [Newborn screening](https://durgical.com/en/biochemistry/topics/newborn-screening/) - [Chromatography](https://durgical.com/en/biochemistry/topics/chromatography/) - [Amino acids: structure, charge and pKa](https://durgical.com/en/biochemistry/topics/amino-acids-structure-charge-and-pka/) ## In embryology - [Maternal diabetes and obesity as teratogens](https://durgical.com/en/embryology/maternal-diabetes-and-obesity-as-teratogens/) ## Why it happens - [How a single gene causes disease: enzymes, receptors and structural proteins](https://durgical.com/en/general-pathology/how-a-single-gene-causes-disease-enzymes-receptors-and-structural-proteins/) - [Mendelian inheritance: autosomal dominant, recessive and X-linked](https://durgical.com/en/general-pathology/mendelian-inheritance-autosomal-dominant-recessive-and-x-linked/) ## What it is An inherited disease in which [liver](https://durgical.com/en/anatomy/liver/) phenylalanine hydroxylase activity is missing. Phenylalanine rises in blood and is toxic to the developing brain. ## Who gets it Its frequency varies by population; in the United States it is about 1 in 25,000 newborns. In Colombia, Law 1980 of 2019 created the newborn screening programme, which allows detection at birth. ## Causes - Variants in both alleles of the PAH gene (autosomal recessive) - Less often, defects in BH4 synthesis or recycling ## Risk factors - Carrier parents - Consanguinity ## Pathophysiology Without phenylalanine hydroxylase, phenylalanine is not turned into tyrosine. It builds up and is shunted to phenylpyruvate and phenylacetate, which appear in urine. High phenylalanine competes with other large amino acids for entry into the brain, disturbs myelin and lowers dopamine and serotonin synthesis. Lack of tyrosine reduces melanin. ## Classification - Classic PKU: almost no activity, very high phenylalanine - Mild or moderate PKU - Mild hyperphenylalaninaemia - Hyperphenylalaninaemia from BH4 deficiency ## Symptoms and signs - Untreated: developmental delay and intellectual disability - Musty or mousy odour of urine, [skin](https://durgical.com/en/anatomy/skin/) and sweat - Lighter skin, hair and eyes - Eczema - Seizures and behaviour problems ## Red flags - Positive newborn screen without follow-up - Pregnancy in a woman with PKU without phenylalanine control ## Diagnosis **Clinical** Today it is almost always found by newborn screening, before symptoms. **Tests** Phenylalanine on a heel-prick blood spot, then in plasma; high phenylalanine/tyrosine ratio; pterin and dihydropteridine reductase tests to rule out BH4 deficiency; PAH gene testing. **Imaging** Brain MRI may show [white matter](https://durgical.com/en/anatomy/white-matter-of-telencephalon/) changes in poorly controlled patients; it is not needed for diagnosis. ## Treatment **Lifestyle** Lifelong low-phenylalanine diet, with a special phenylalanine-free amino acid formula and low-protein foods **Medical** Sapropterin (BH4) in patients who respond **Medical** Pegvaliase, an enzyme that breaks down phenylalanine, in selected adults **Follow-up** Regular blood phenylalanine checks, stricter before and during pregnancy ## Complications - Irreversible intellectual disability if treatment starts late - Maternal PKU syndrome in the child: microcephaly, heart disease and low birth weight - Anxiety, depression and attention problems in poorly controlled adults ## Prognosis With treatment from the first weeks of life, intellectual development is usually normal. ## Prevention - Universal newborn screening - Phenylalanine control before conception in women with PKU - Genetic counselling ## Test yourself Think of the answer, then tap the question to see it. ## Which enzyme is missing in classic phenylketonuria? Liver phenylalanine hydroxylase, which turns phenylalanine into tyrosine. ## Why do untreated patients have light skin and hair? Tyrosine is short and high phenylalanine inhibits tyrosinase, so less melanin is made. ## What is maternal PKU syndrome? Harm to the fetus (microcephaly, heart disease, intellectual disability) when a mother with PKU has high phenylalanine in pregnancy. ## Why is BH4 deficiency ruled out in every newborn with high phenylalanine? Because dopamine and serotonin synthesis also fail and the treatment is different. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/conditions/phenylketonuria/) ## Related conditions - [Oculocutaneous albinism](https://durgical.com/en/conditions/oculocutaneous-albinism/) - [Epilepsy and seizures](https://durgical.com/en/conditions/epilepsy-and-seizures/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Phenylketonuria: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/phenylketonuria/) (MedlinePlus, US National Library of Medicine, 2026); [PAH gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/pah/) (MedlinePlus, US National Library of Medicine, 2026); [Newborn screening tests: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/007257.htm) (MedlinePlus, US National Library of Medicine, 2026). [← All conditions](https://durgical.com/en/conditions/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/conditions/phenylketonuria/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/phenylketonuria/