Phenylketonuria

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Phenylketonuria
Chemical structure of phenylalanine
Synonyms	PKU
Pronounce
Specialty	Medical genetics
Symptoms	Intellectual disability, seizures, behavioral problems, mental disorders, musty smell
Complications	N/A
Onset	Symptoms develop gradually
Duration	Lifelong
Types	N/A
Causes	Genetic mutation in the PAH gene
Risks	Family history
Diagnosis	Newborn screening, blood test
Differential diagnosis	Hyperphenylalaninemia, biopterin deficiency
Prevention	Dietary management
Treatment	Low-phenylalanine diet, sapropterin
Medication	Sapropterin, pegvaliase
Prognosis	Good with treatment
Frequency	1 in 12,000 births
Deaths	Rare with treatment

Phenylketonuria (PKU) is a rare genetic disorder characterized by the inability to metabolize the amino acid phenylalanine. This condition is caused by a deficiency in the enzyme phenylalanine hydroxylase, which is necessary for converting phenylalanine to tyrosine.

Genetics

Autosomal recessive inheritance pattern

PKU is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the defective gene, one from each parent, to be affected by the disorder. The gene responsible for PKU is located on chromosome 12.

Pathophysiology

In individuals with PKU, the accumulation of phenylalanine in the body can lead to a variety of health problems. High levels of phenylalanine can cause damage to the brain and nervous system, leading to intellectual disability and other neurological issues.

Clinical Features

Microcephaly is a possible feature of untreated PKU

Symptoms of PKU can vary but often include intellectual disability, microcephaly, seizures, and behavioral problems. If untreated, PKU can lead to severe developmental delays and neurological complications.

Diagnosis

Newborn screening for PKU

PKU is typically diagnosed through newborn screening programs, which test for elevated levels of phenylalanine in the blood. Early detection is crucial for preventing the adverse effects of the disorder.

Treatment

The primary treatment for PKU is a phenylalanine-restricted diet, which involves limiting the intake of foods high in phenylalanine, such as meat, dairy, and nuts. Special medical formulas and foods are often used to ensure adequate nutrition while maintaining low phenylalanine levels.

Complications

If PKU is not managed properly, individuals may experience severe intellectual disability, behavioral problems, and other neurological issues. Pregnant women with PKU must maintain strict control of their phenylalanine levels to prevent maternal PKU syndrome, which can affect the developing fetus.

Prevention

Warning label for phenylketonurics

Genetic counseling is recommended for families with a history of PKU. Prenatal testing and carrier screening can help identify at-risk pregnancies and individuals.

See also

• Inborn errors of metabolism
• Amino acid metabolism
• Genetic disorders

Metabolic pathway of phenylalanine and tyrosine

See Also

• Tyrosinemia
• Alkaptonuria
• Maple syrup urine disease