Introduction
Phenylalanine hydroxylase (PAH) deficiency is an autosomal recessive disorder also know as phenylketonuria (PKU). (1,2,3) This disease results from mutations in the phenylalanine hydroxylase gene, making the body unable to utilize the amino acid phenylalanine properly. (1) Phenylalanine hydroxylase converts phenylalanine to tyrosine. Without adequate phenylalanine hydroxylase levels, phenylalanine accumulates which can lead to toxic levels in the blood. Buildup of phenylalanine can be toxic to the brain causing impaired development leading to severe and irreversible mental disability. (1,3) PKU is one of the most common inborn diseases of amino acid metabolism, and is classified based on the severities of phenylalanine levels and …show more content…
Dietary intake and the recycling of amino acid stores are sources of phenylalanine. The first step in the catabolism is the irreversible conversion of phenylalanine to tyrosine by PAH. (1) Phenylalanine hydroxylase requires tetrahydrobiopterin as a co-factor. (1) PKU develops due to deficiency in or absence of phenylalanine hydroxylase. Deficiency in the PAH enzyme results in elevated phenylalanine and reduced levels of tyrosine. When the pathway to tyrosine is blocked, excess phenylalanine is transaminated to phenylpyruvic acid and excreted in urine. (1)
PKU is caused by mutations in the PAH gene and is an inherited disorder. (1,2) Phenylalanine is an essential amino acid metabolized in the liver by PAH. This recessive mutation makes the body unable to properly process the amino acid phenylalanine into tyrosine because of the lack of PAH. As a result, the amino acid builds up in blood and surrounding tissues and is toxic to the neurons in the brain. For an individual to have PKU, both the mother and father must pass on the mutated phenylalanine hydroxylase gene. …show more content…
Those with the disease can maintain appropriate levels of phenylalanine in the brain through monitoring with blood testing and subsequent diet adjustment. A diet low in protein and free from phenylalanine is important to maintain brain functions. (1) The brain requires amino acids including phenylalanine for building brain proteins and building neurotransmitters. (1,2) The more phenylalanine in the blood, the more that gets transported into the brain. This causes less of the other essential amino acids to be transported affecting normal brain function. (1) Brain magnetic resonance imaging (MRI) commonly shows abnormalities in the cerebral white matter in individuals affected by PKU. (1) Evidence suggests that changes in PAH function in PKU can cause lower amounts of dopamine in the brain. (1,2) Treatment is predominately changing the individuals diet, but recently the medication sapropterin has become approved. (1) Sapropterin stimulates PAH helping break down phenylalanine, preventing build up in the blood. The goal of any treatment is to lower blood phenylalanine to reduce the risk of damaging brain
Phenylalanine hydroxylase (PAH) deficiency is an autosomal recessive disorder also know as phenylketonuria (PKU). (1,2,3) This disease results from mutations in the phenylalanine hydroxylase gene, making the body unable to utilize the amino acid phenylalanine properly. (1) Phenylalanine hydroxylase converts phenylalanine to tyrosine. Without adequate phenylalanine hydroxylase levels, phenylalanine accumulates which can lead to toxic levels in the blood. Buildup of phenylalanine can be toxic to the brain causing impaired development leading to severe and irreversible mental disability. (1,3) PKU is one of the most common inborn diseases of amino acid metabolism, and is classified based on the severities of phenylalanine levels and …show more content…
Dietary intake and the recycling of amino acid stores are sources of phenylalanine. The first step in the catabolism is the irreversible conversion of phenylalanine to tyrosine by PAH. (1) Phenylalanine hydroxylase requires tetrahydrobiopterin as a co-factor. (1) PKU develops due to deficiency in or absence of phenylalanine hydroxylase. Deficiency in the PAH enzyme results in elevated phenylalanine and reduced levels of tyrosine. When the pathway to tyrosine is blocked, excess phenylalanine is transaminated to phenylpyruvic acid and excreted in urine. (1)
PKU is caused by mutations in the PAH gene and is an inherited disorder. (1,2) Phenylalanine is an essential amino acid metabolized in the liver by PAH. This recessive mutation makes the body unable to properly process the amino acid phenylalanine into tyrosine because of the lack of PAH. As a result, the amino acid builds up in blood and surrounding tissues and is toxic to the neurons in the brain. For an individual to have PKU, both the mother and father must pass on the mutated phenylalanine hydroxylase gene. …show more content…
Those with the disease can maintain appropriate levels of phenylalanine in the brain through monitoring with blood testing and subsequent diet adjustment. A diet low in protein and free from phenylalanine is important to maintain brain functions. (1) The brain requires amino acids including phenylalanine for building brain proteins and building neurotransmitters. (1,2) The more phenylalanine in the blood, the more that gets transported into the brain. This causes less of the other essential amino acids to be transported affecting normal brain function. (1) Brain magnetic resonance imaging (MRI) commonly shows abnormalities in the cerebral white matter in individuals affected by PKU. (1) Evidence suggests that changes in PAH function in PKU can cause lower amounts of dopamine in the brain. (1,2) Treatment is predominately changing the individuals diet, but recently the medication sapropterin has become approved. (1) Sapropterin stimulates PAH helping break down phenylalanine, preventing build up in the blood. The goal of any treatment is to lower blood phenylalanine to reduce the risk of damaging brain