Phenylketonuria (PKU) is an autosomal recessive genetic disorder that is inherited due to a contribution of the genetic disorder gene from each parent. Phenylketonuria is due to a variety of mutations to the gene of the liver enzyme phenylalanine hydroxylase (PAH) (Vockley 2014). Mutations of this enzyme result in its dysfunction and deficiency in the liver. There are over 300 possible mutations of the gene that makes this enzyme (Nowacki 1998). Each mutation has been associated with varying severity of the phenylalanine hydroxylase’s dysfunction, which results in the varying severity of physical symptoms of PKU (Pey 2003). Dysfunctional PAH cannot do its job of converting the amino acid phenylalanine to another amino acid tyrosine. Amino acids are the building blocks of all proteins in cells and are essential for life, but too much of certain amino acids can result in many toxic effects to the body. One of the PAH’s essential roles in the liver is to maintain non-toxic phenylalanine levels by converting phenylalanine to tyrosine. In phenylketonuria, phenylalanine hydroxylase is not able to convert excess phenylalanine to tyrosine which results in high concentrations of the amino acid phenylalanine in the blood. The high concentrations of phenylalanine in the blood result in the production of these compounds called phenylketones, which is where the disorder gets its name (Vockley 2014). High levels of phenylalanine in the blood, if left at high concentrations without treatment, have been shown to result in severe physical and mental disability (Embury 2007) (Moraes 2013). Neurological symptoms include mental retardation, social and behavior problems, seizures, and decreased IQ (Vockley 2014).
How PKU and normal individuals differ with regards to conversion of phenylalanine Screening for the presence of the phenylketone compounds has led to early detection of newborns with phenylketonuria, resulting in a decrease in levels of mental and physical disability with early treatment (Vockley 2014). The most common treatment suggested by doctors is the life-long implementation of a phenylalanine-free diet to keep phenylalanine levels low in the blood (Vockley 2014).
Phenylalanine-free diet suggested foods Phenylalanine is present in many of the foods we eat. A lifelong phenylalanine-free diet has resulted in PKU patients experiencing normal cognitive function (Vockley 2014). A newly approved drug on the market called sapropterin has improved phenylalanine tolerance in the body, by making the enzyme more efficient via ensuring proper folding of the protein (Cunningham 2012). This drug coupled with the lifelong diet has demonstrated success with many PKU patients, thus allowing these individuals to maintain normal cognitive function (Simon 2008).
Simplified PKU pathway resulting in the production of phenylketones
Molecular Basis of the Disease State
The title of this page drew me in instantly. I had no idea what Phenylketonuria was and I wanted to find out because of the title. This page does a very good job of taking it slow to explain the effects of this disease on the body. Even something as simple as reminding the reader of what amino acids do is a very helpful tool for a reader lacking a science background. The implementation of graphics throughout the page are helpful and on point, located right after the body of text that they refer to. This is a very minor critique, but implying that there is a “normal” life seems like a generalizing statement that oversteps it bounds. I think it would be just as good of a concluding statement to end with “This drug coupled with the lifelong diet has demonstrated success with many PKU patients, thus allowing these individuals to maintain normal cognitive function.”
Thanks you for your comment. I agree that what I said might have over-stepped the bounds of interpretation of the literature. I will remove that last comment. It is interesting though that just with a constant low phenylalanine diet can drastically change the neurological pathology of the disease, in which the negative effects on the brain in PKU are not visible and have significantly less impact on their normal lives.