Phenylketonuria

Phenylketonuria (PKU) is a genetic metabolic disorder where the body cannot properly break down the amino acid phenylalanine. Without treatment, this condition can cause intellectual disability, seizures, behavioral issues, and mental disorders, along with a musty body odor and unusually light skin. It is inherited when a child receives two mutated copies of the PAH gene—one from each parent. This gene normally provides instructions for making the enzyme phenylalanine hydroxylase, which processes excess phenylalanine. When the enzyme is missing or doesn't work well, phenylalanine builds up to harmful levels. People with just one mutated gene copy are carriers and usually have no symptoms. There are two main types: classic PKU, where almost no enzyme works, and variant PKU, where some function remains.

Newborns with PKU appear normal at birth because the mother's body handles phenylalanine during pregnancy. For this reason, the disease is not detectable by physical exam, so many countries screen newborns using a blood sample from a heel prick, typically taken two to seven days after birth. This test can show high phenylalanine levels after a day or two of normal feeding. If a child isn't diagnosed early and doesn't start a low-phenylalanine diet, blood levels rise over time. Toxic amounts of phenylalanine, along with low levels of tyrosine, can permanently harm infant development. Untreated children may have seizures, very fair hair and skin, and a musty or mousy odor in sweat and urine from phenylacetate. They often miss early developmental milestones, develop a small head, and show worsening brain function. Later in life, hyperactivity, abnormal brain waves, seizures, and severe learning disabilities are common. A musty smell and a tendency toward eczema can persist without treatment. Brain damage from the first months of life is not reversible. However, children detected at birth and treated are much less likely to have these neurological problems, though they still face higher risks for conditions like asthma, eczema, anemia, weight gain, kidney issues, osteoporosis, stomach problems, kidney stones, and high blood pressure. Mood disorders occur 230% more often than in the general population, dizziness 180% more, and chronic heart disease, asthma, diabetes, and stomach infections 170% more.