What is Phenylketonuria?

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).

How PKU and normal individuals differ with regards to conversion of phenylalanine
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-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 (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 and carry out normal lives (Simon 2008).

Simplified PKU pathway resulting in the production of phenylketones
Simplified PKU pathway resulting in the production of phenylketones

5 Replies to “What is Phenylketonuria?”

  1. 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.”

  2. Really thorough title page and very good description of the pathway that causes the enzymopathy. What type of phenotypes or symptoms indicate this disease? In other words, in what ways does this accumulation of phenylalanine and deficiency of tyrosine impact cellular function? I know you mentioned it can cause physical and mental disabilities but what types of disabilities?

    1. Thank you Tyler for your comment. I do have more symptoms that I can discuss such as seizures, serious behavioral and social problems, stunted growth, decreased IQ levels, increased occurrences of eczema, mental retardation, fair skin, and an overall musty odor as well as in the urine. These symptoms have not been seen in many years though because of the screening of the disease by the Guthrie test as an infant. This results in instant implementation of a low phenylalanine diet which eliminates the presence of many of these symptoms. However, some of these symptoms are observed in more severe cases of PKU.

  3. This is a great and thorough overview of the disease and provides great background information. The one nit-picky thing I’m gonna write is that vocab with the primer page. I know that you’ve added definitions into the primer, but linking would show the reader that this word is defined as a resource on the website.
    You point out the function of PAH in the liver is the conversion of phenylalanine to tyrosine. However, I’m curious as to the function of PAH in other cells of the body, it would most likely be the same thing, but what is the effect of phenylalanine accumulation in those other tissues and cells? I’m also curious as to how the phenotype associated with this disease is manifested?

    1. Kat thanks for your comments. I made the mistake of posting this page to the whole blog and not linking it specifically to the disease. The other title page that I created does have links to the biochemistry primer page. This enzyme has been known to act primarily in the liver, however the effect of phenylalanine accumulation does have an effect at other organs in the body. This accumulation of phenylalanine actually enters the blood stream, and has shown over accumulation in the brain as well. The direct connection between phenylalanine levels in the brain and neurological pathology has not been defined, but many theories about potential links have been identified. Phenotype manifestation is a lingering question in the literature at the current moment.

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