Phenylketonuria (PKU) - Symptoms and Causes

Overview

• PKU is a rare inherited disorder leading to an amino acid, phenylalanine, buildup in the body.
• Caused by a change in the PAH gene affecting enzyme production necessary for breaking down phenylalanine.
• Dangerous buildup occurs when consuming protein-rich foods or aspartame.
• Lifelong dietary restrictions are essential, although new medications may offer a more flexible diet.
• Early screening and treatment can prevent severe intellectual and health complications.

Symptoms

• Newborns with PKU initially asymptomatic; symptoms appear within months if untreated.
• Symptoms include:
  • Musty odor in breath, skin, or urine
  • Neurological issues, including seizures
  • Skin rashes such as eczema
  • Lighter skin, hair, and eye color
  • Small head size (microcephaly)
  • Hyperactivity
  • Intellectual disability
  • Developmental delays
  • Behavioral, emotional, and social issues
  • Mental health disorders

Severity

• Classic PKU: Most severe form; enzyme missing or minimal, causing severe brain damage.
• Less Severe Forms: Some enzyme function remains, reducing phenylalanine levels and brain damage risk.
• Special diets remain crucial across all forms to prevent complications.

Pregnancy and PKU

• Maternal PKU: High phenylalanine levels in pregnant women can harm the developing baby.
• Risks include low birth weight, small head size, heart issues, developmental delays, and intellectual disability in the child.
• Women should adhere to a PKU diet before and during pregnancy.

When to See a Doctor

• Newborns: Immediate treatment following abnormal screening results is crucial.
• Women of Childbearing Age: Adherence to PKU diet is vital pre and during pregnancy.
• Adults: Lifelong PKU care is necessary; returning to the diet may improve cognitive function for those who ceased in adolescence.

Causes

• Autosomal recessive inheritance pattern: Two changed genes needed, one from each parent.
• PKU results from PAH gene mutations affecting enzyme production.
• Phenylalanine-rich foods, such as milk, cheese, nuts, and artificial sweeteners, can cause buildup.

Risk Factors

• Inheritance: Both parents must carry the gene.
• Ethnic Descent: More common in people of European ancestry in the U.S.

Complications

• Untreated PKU can cause irreversible brain damage, intellectual disability, neurological issues, and behavioral problems.

Prevention

• Low-Phenylalanine Diet: Essential for women with PKU to prevent harm to unborn babies.
• Genetic Counseling: Recommended for individuals or families with PKU for informed family planning.