Phenylketonuria (PKU) - Symptoms and Causes

Overview

• Phenylketonuria (PKU): A rare inherited disorder leading to a buildup of the amino acid phenylalanine in the body.
• Cause: Change in the phenylalanine hydroxylase (PAH) gene.
• Mechanism: Lack of enzyme needed to break down phenylalanine causing buildup, especially when consuming protein-rich foods or aspartame.
• Management: Requires a lifelong diet low in phenylalanine to prevent intellectual disabilities and other health issues.
• Screening: Newborn screening is common in the U.S. to detect and start treatment early.

Symptoms

• Newborns may not show symptoms initially, but untreated PKU symptoms appear within a few months:
  • Musty odor in breath, skin, urine due to phenylalanine buildup.
  • Neurological issues including seizures.
  • Skin rashes like eczema.
  • Lighter skin, hair, and eyes due to lack of melanin production.
  • Microcephaly (small head size).
  • Hyperactivity and intellectual disability.
  • Developmental delays and mental health disorders.

Severity Variations

• Classic PKU: Most severe, almost no enzyme activity, high phenylalanine levels leading to severe brain damage.
• Less severe forms: Partial enzyme activity, lower phenylalanine levels, less risk of brain damage.
• All forms require dietary management.

Pregnancy and PKU

• Risk of maternal PKU if diet is not followed during pregnancy leading to high phenylalanine levels.
• Affects the unborn child causing low birth weight, small head size, heart problems, developmental delays, and intellectual disabilities.

Causes

• Genetics: Autosomal recessive; both parents must carry and pass on the altered gene.
• Gene Mutation: Affects phenylalanine hydroxylase gene reducing enzyme production.

Inheritance

• Both parents must pass the changed gene for PKU to manifest in the child.
• Carriers (one changed gene) don’t show symptoms.

Risk Factors

• Both parents carrying the PKU gene.
• More common in individuals of European ancestry in the U.S.

Complications

• Untreated PKU can lead to:
  • Irreversible brain damage and intellectual disability.
  • Seizures, tremors, behavioral issues.
  • Pregnant women with PKU can harm their unborn child if not managing phenylalanine levels.

Prevention and Management

• Diet: Low phenylalanine diet, especially crucial for women planning pregnancy or pregnant.
• Genetic Counseling: Recommended for those with a family history of PKU or carriers.

Conclusion

• Early detection and lifelong management are crucial to preventing complications associated with PKU through dietary and medical interventions.