7085. Genetics. Phenylketonuria

Genetic testing to identify mutations in the PAH gene that cause an inherited disorder of phenylalanine metabolism – phenylketonuria (PKU). The test can confirm the diagnosis, identify carrier status, or assess the risk to offspring.

Phenylketonuria (PKU) is an autosomal recessive inherited disorder caused by pathogenic changes in the PAH (phenylalanine hydroxylase) gene. This gene encodes the enzyme phenylalanine hydroxylase, which converts L-phenylalanine (an essential amino acid) into tyrosine.

Mutations in PAH cause the enzyme to lose activity, leading to the accumulation of phenylalanine and its toxic metabolites (phenylpyruvic and phenyllactic acids) in the blood. Concurrently, levels of tyrosine, an important precursor of dopamine, melanin, adrenaline, and thyroid hormones, are reduced.

If the disease is not diagnosed promptly, it leads to severe damage to the nervous system, mental retardation, seizures, microcephaly, and behavioral and motor disorders.

More than 1,000 mutations of the PAH gene are known, of which over 400 are pathogenic (according to NCBI).

• Infants and children with suspected PKU or based on neonatal screening results.
• Parents who are potential carriers of the RAS gene (especially if there is a history of PKU in the family).
• Couples planning a pregnancy or IVF – to exclude the risk of having a child with PKU.
• As part of expanded screening programs to detect hereditary metabolic disorders.
• In adults – if hyperammonemia, cognitive impairment of unknown origin, or psychomotor retardation are detected.

• Venous blood

In order to exclude factors that may affect the test results, we recommend to follow the preparation rules: