Newborns with PKU initially don't have any symptoms. However, without treatment, babies usually develop signs of PKU within a few months.

PKU signs and symptoms can be mild or severe and may include:

• A musty odor in the breath, skin or urine, caused by too much phenylalanine in the body
• Neurological problems that may include seizures
• Skin rashes (eczema)
• Fair skin and blue eyes, because phenylalanine can't transform into melanin — the pigment responsible for hair and skin tone
• Abnormally small head (microcephaly)
• Hyperactivity
• Intellectual disability
• Delayed development
• Behavioral, emotional and social problems
• Psychiatric disorders

Severity varies

The severity of PKU depends on the type.

• Classic PKU. The most severe form of the disorder is called classic PKU. The enzyme needed to convert phenylalanine is missing or severely reduced, resulting in high levels of phenylalanine and severe brain damage.
• Less severe forms of PKU. In mild or moderate forms, the enzyme retains some function, so phenylalanine levels are not as high, resulting in a smaller risk of significant brain damage.

But most children with the disorder still require a special PKU diet to prevent intellectual disability and other complications.

Pregnancy and PKU

Women who have PKU and become pregnant are at risk of another form of the condition called maternal PKU. If women don't follow the special PKU diet before and during pregnancy, blood phenylalanine levels can become high and harm the developing fetus or cause a miscarriage.

Even women with less severe forms of PKU may place their unborn children at risk by not following the PKU diet.

Babies born to mothers with high phenylalanine levels don't often inherit PKU. But they can have serious consequences if the level of phenylalanine is high in the mother's blood during pregnancy. Complications at birth may include:

• Low birth weight
• Delayed development
• Facial abnormalities
• Abnormally small head
• Heart defects and other heart problems
• Intellectual disability
• Behavioral problems

A defective gene (genetic mutation) causes PKU, which can be mild, moderate or severe. In a person with PKU, this defective gene causes a lack of or deficiency of the enzyme that's needed to process phenylalanine, an amino acid.

A dangerous buildup of phenylalanine can develop when a person with PKU eats protein-rich foods, such as milk, cheese, nuts or meat, and even grains such as bread and pasta, or eats aspartame, an artificial sweetener. This buildup of phenylalanine results in damage to nerve cells in the brain.

Inheritance

For a child to inherit PKU, both the mother and father must have and pass on the defective gene. This pattern of inheritance is called autosomal recessive.

It's possible for a parent to be a carrier — to have the defective gene that causes PKU, but not have the disease. If only one parent has the defective gene, there's no risk of passing PKU to a child, but it's possible for the child to be a carrier.

Most often, PKU is passed to children by two parents who are carriers of the disorder, but don't know it.

Risk factors for inheriting PKU include:

• Having both parents with a defective gene that causes PKU. Two parents must pass along a copy of the defective gene for their child to develop the condition.
• Being of certain ethnic descent. The gene defect that causes PKU varies by ethnic groups and it's less common in African-Americans than in other ethnic groups.

Untreated PKU can lead to complications in infants, children and adults with the disorder. When mothers with PKU have high blood phenylalanine levels during pregnancy, fetal birth defects or miscarriage can occur.

Untreated PKU can lead to:

• Irreversible brain damage and marked intellectual disability beginning within the first few months of life
• Neurological problems such as seizures and tremors
• Behavioral, emotional and social problems in older children and adults
• Major health and developmental problems