Phenylalanine Hydroxylase Deficiency

Phenylalanine hydroxylase deficiency is an inherited disorder that is characterized by increased levels of phenylalanine in the blood. This is due to a lack of the enzyme phenylalanine hydroxylase. If untreated, individuals with phenylalanine hydroxylase deficiency can develop symptoms including intellectual disability, seizures, behavioral problems, and psychiatric disorders. Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body. Women who have phenylalanine hydroxylase deficiency and are pregnant must be carefully managed to reduce risk of exposure of high levels of phenylalanine to the baby. The severity of this disease can be decreased significantly by a low-protein diet and use of a Phe-free medical formula as soon as possible after birth. If identified right after birth and diet treatment is strictly followed, the outcome of children with phenylalanine hydroxylase deficiency is expected to be good. Delayed treatment can damage the brain and cause irreversible intellectual disability and psychiatric problems. Phenylalanine hydroxylase deficiency is caused by pathogenic variants in the PAH gene.

Phenylalanine hydroxylase deficiency is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for phenylalanine hydroxylase deficiency. However, the risk to have a child affected with phenylalanine hydroxylase deficiency is increased. Testing of reproductive partners is recommended for carriers of phenylalanine hydroxylase deficiency.

The frequency of phenylalanine hydroxylase deficiency varies among different ethnicities. In the United States, phenylalanine hydroxylase deficiency occurs in 1 in 10,000 to 15,000 newborns, with the highest occurrence among Caucasians, or those of European descent.

Genetics Home Reference: Phenylketonuria (http://ghr.nlm.nih.gov/)

OMIM [Phenylketonuria: 261600] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Phenylketonuria (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing