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Phenylketonuria
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Phenylketonuria

Phenylketonuria (PKU) is an inherited disorder that causes the amino acid phenylalanine to build up to toxic levels in the body, potentially leading to serious health issues if left untreated.

Overview

Phenylketonuria, commonly known as PKU, is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. Phenylalanine is a protein building block obtained from certain foods—such as meat, eggs, nuts, and milk—and some artificial sweeteners. If PKU is not treated, phenylalanine can build up to harmful levels, causing intellectual disability and other serious health problems.

Symptoms

The signs and symptoms of PKU vary from mild to severe. The most severe form is known as classic PKU.

  • Infants: Appear normal until a few months old. Without treatment, they develop permanent intellectual disability.
  • Developmental and Behavioral: Seizures, delayed development, behavioral problems, and psychiatric disorders are common.
  • Physical Characteristics: Untreated individuals may have a musty or mouse-like odor. Children with classic PKU often have lighter skin and hair than unaffected family members and are prone to skin disorders such as eczema.
  • Pregnancy Complications: Babies born to mothers with PKU who do not follow a low-phenylalanine diet are at risk of intellectual disability, low birth weight, slow growth, heart defects, and an abnormally small head size.

Less severe forms, such as variant PKU and non-PKU hyperphenylalaninemia, carry a smaller risk of brain damage, and very mild cases may not require treatment.

Treatment & Management

PKU is managed primarily through a diet low in phenylalanine. Because this substance is found in all proteins, management includes:

  • Avoiding meat, dairy, nuts, tofu, and other high-protein foods.
  • Using low-protein formulas for infants.
  • Limiting intake to specific fruits, vegetables, and foods containing fats and sugars.
  • Avoiding the artificial sweetener aspartame, which contains high amounts of phenylalanine.

Because safe consumption levels vary, individuals should work with a healthcare professional to develop an individualized diet.

Causes & Risk Factors

PKU is caused by variants (mutations) in the PAH gene, which provides instructions for making the enzyme phenylalanine hydroxylase. This enzyme converts phenylalanine into other important compounds. When the enzyme is altered or absent, phenylalanine builds up to toxic levels, which is particularly damaging to nerve cells in the brain.

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell must have a variant to cause the disorder. Parents of an affected individual typically carry one copy of the altered gene but do not show signs or symptoms.

Frequently Asked Questions

Clinical consensus guidelines recommend maintaining blood phenylalanine (Phe) levels between 120 and 360 micromoles per liter (2 to 6 milligrams per deciliter) for infants, children, and adolescents to prevent cognitive impairment, behavioral issues, and structural brain changes. For adults, maintaining levels below 360 micromoles per liter remains ideal, though some centers accept levels up to 600 micromoles per liter if the individual is asymptomatic and cognitively stable. However, for women planning pregnancy or actively pregnant, strict control between 120 and 360 micromoles per liter is mandatory to avoid maternal PKU syndrome.
dults who discontinue dietary management often experience neuropsychiatric symptoms, colloquially termed "brain fog," which includes difficulty with working memory, reduced executive functioning, slow processing speed, tremors, anxiety, depression, and severe fatigue. Sustained high Phe levels can also produce white matter changes visible on brain MRI. Resuming a Phe-restricted diet or starting targeted medical therapy can reverse most of these cognitive and mood symptoms and substantially improve daily functioning, regardless of how long the person was off diet.
Beyond medical foods and low-protein formulations, two major pharmacological therapies exist. Sapropterin dihydrochloride (Kuvan), a synthetic form of the enzyme cofactor tetrahydrobiopterin (BH4), helps increase enzyme activity in a subset of patients with residual phenylalanine hydroxylase activity (BH4-responsive PKU). For adults with uncontrolled Phe levels despite diet, pegvaliase-pqpz (Palynziq) is an injectable enzyme substitution therapy that breaks down phenylalanine directly in the bloodstream, though it requires careful monitoring for systemic allergic reactions.
Maternal PKU syndrome occurs when high maternal blood phenylalanine crosses the placenta, acting as a direct teratogen on the developing fetus. Uncontrolled levels during pregnancy cause microcephaly, congenital heart defects, intrauterine growth restriction, and severe intellectual disability in the baby, even if the baby does not inherit PKU. To prevent this, women with PKU must achieve rigorous metabolic control (blood Phe 120 to 360 micromoles per liter) for at least three consecutive months before conception and maintain this tight range throughout entire gestation under close metabolic and nutritional supervision.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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