What's phenylketonuria?
Phenylketonuria (PKU) is an inherited condition in which the body cannot properly break down the amino acid phenylalanine, so it builds up and can harm the developing brain.
| Also indexed as | OMIM:261600, MONDO:0009861 |
|---|---|
| Features mapped | 12 |
| Treatments mapped | 5 |
| Published sources | 9 |
| Last reviewed | 2026-08-04 |
Signs and symptoms
Hyperphenylalaninemia
A high blood level of phenylalanine (hyperphenylalaninaemia) is the central problem in PKU and, untreated, can affect brain function.
Reduced phenylalanine hydroxylase level
PKU is caused by reduced activity of the enzyme phenylalanine hydroxylase (PAH), which normally converts phenylalanine to tyrosine.
Seizure
If phenylalanine levels stay high and untreated, seizures can occur.
Hyperactivity
Hyperactivity is reported more often in people with phenylketonuria than in the general population, and it is one of the neuropsychiatric symptoms linked to the condition.
Anxiety
Anxiety is reported more often in people with phenylketonuria than in the general population, and it is one of the neuropsychiatric symptoms linked to the condition.
Intellectual disability
Untreated high phenylalanine levels can lead to intellectual disability, which is why early management matters.
Attention deficit hyperactivity disorder
Inattention is reported more often in people with phenylketonuria than in the general population, and it is one of the neuropsychiatric symptoms linked to the condition.
Depression
Depression is reported more often in people with phenylketonuria than in the general population, and it is one of the neuropsychiatric symptoms linked to the condition.
Autosomal recessive inheritance
PKU is passed on in an autosomal recessive pattern, requiring a changed gene copy from both parents.
Microcephaly
In pregnancies affected by phenylketonuria, an abnormally small head (microcephaly) in the baby is more common when the mother's phenylalanine is not kept within the target range, and less common when phenylalanine is well controlled from before conception.
Maternal hyperphenylalaninemia
When a person with phenylketonuria is pregnant, high phenylalanine levels can affect the developing baby, a situation sometimes called maternal PKU syndrome. Keeping phenylalanine well controlled during pregnancy is associated with lower risks of miscarriage, heart defects, a small head, and problems with the baby's brain development.
Pregnancy history
For someone with phenylketonuria, the period before and during pregnancy matters: reaching a phenylalanine level at or below 360 micromoles per liter before conception is strongly recommended to lower the chance of pregnancy complications and harm to the baby.
How it is diagnosed
Phenylketonuria
Diagnosed using: Newborn blood spot screening.
“Since 1969, the newborn dried blood spot test has remained the main method of early screening and diagnosis for PKU.”
Phenylketonuria
Diagnosed using: PAH genetic testing.
“…genetic testing for PAH variants is recommended at birth to confirm diagnosis and guide…”
Phenylketonuria
Diagnosed using: blood phenylalanine monitoring.
“Phenylketonuria (PKU) management requires weekly blood phenylalanine (Phe) monitoring.”
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
Sapropterin
Sapropterin is a medicine that can lower phenylalanine levels in some people with PKU, used alongside dietary management.
Used to help with: Phenylketonuria.
“Pharmacological interventions such as sapropterin, sepiapterin and pegvaliase can also be used as treatment adjuncts in patients with PKU.”
Phenylalanine-restricted diet
The main treatment for phenylketonuria is a lifelong diet that limits phenylalanine, with the goal of keeping blood phenylalanine levels down.
Used to help with: Phenylketonuria.
“The primary therapeutic management is a lifelong phenylalanine-restricted diet with the aim of decreasing plasma Phe levels.”
Pegvaliase
Pegvaliase (brand name Palynziq) is an injectable enzyme medicine approved in 2018 to help manage phenylalanine levels in adults with phenylketonuria.
Used to help with: Phenylketonuria.
“Pegvaliase (Palynziq®), pegylated phenylalanine ammonia lyase (PAL), was approved in 2018 to manage Phe levels in adults with PKU.”
Sepiapterin
Sepiapterin (brand name Sephience) is an oral medicine for children and adults with phenylketonuria. It was approved in 2025 in several countries, including the United States.
Used to help with: Phenylketonuria.
“In 2025, sepiapterin (Sephience™), a novel oral treatment for children and adults with PKU, was approved in several countries, including the USA.”
low-phenylalanine medical formula
Alongside avoiding high-protein foods, the phenylalanine-restricted diet for phenylketonuria can be supplemented with high-protein medical formulas that are low in phenylalanine, so that protein needs are met without raising phenylalanine levels.
Used to help with: Phenylketonuria.
“The recommended diet consists of avoiding high-protein foods such as meat, fish, eggs and nuts, and can be supplemented with high-protein medical formulas which are low in phenylalanine.”
Triggers to avoid
In this condition, certain drugs, foods, or other exposures can set off an acute episode in people who are affected, even when they are otherwise well. The research mapped here describes the agents below. This is information, not a recommendation: what to avoid and what is safe for any individual is a conversation for their own care team.
Dietary phenylalanine
Dietary phenylalanine is the trigger that must be limited in PKU; a phenylalanine-restricted diet is used to keep blood levels down.
Reported in the research mapped here as able to provoke: Phenylketonuria in people with this condition.
“The primary therapeutic management is a lifelong phenylalanine-restricted diet with the aim of decreasing plasma Phe levels.”
How to read the evidence labels
Where this comes from
This guide is built from 9 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.