Tag Archives: PKU off-diet

Do ‘protective mutations’ hold a cure for PKU?

That’s the question I asked after watching a TED Talk from Stephen Friend, co-founder of Sage Bionetworks. During the presentation, Friend describes an ambitious initiative called the Resilience Project: A Search for Unexpected Heroes, which flips traditional scientific research on its head by suggesting that rather than studying those people who are already sick, we should be studying those people science tells us would be sick with a rare disease, but for some reason have remained healthy.

The premise of the talk, titled The hunt for “unexpected genetic heroes,” asks whether having a closer look at the protective mutations of these “resilient” individuals would provide a pathway for developing new treatments or preventing diseases all together. Here’s the full video presentation:

Naturally, upon finishing the video, I immediately thought the Resilience Project might have some relevance to PKU research. That’s because there are a few, rare cases in the PKU community of individuals who are high-functioning, off-diet phenylketonuria patients, meaning that despite having what is medically considered to be dangerously high phenylalanine levels, these folks are still able to function with a high-level of intellect and lead normal, productive lives.

Friend’s TED Talk ends with a call to action—for individuals to become engaged by voluntarily submitting their DNA to the project—but there was little detail on how to go about doing so. After finding the Resilience Project’s website, and scrolling through much of its content, I was pleasantly surprised to learn that phenylketonuria (PAH) is one of the 195 metabolic gene disorders the group is looking to study. Pretty cool, huh?

After becoming disconnected from the PKU community for the 18 years that I was off-diet, I never did understand why I seemed to function just fine. But as I started to delve back into the world of PKU in 2008, I quickly started to hear in various circles about a mutation theory called the blood-brain barrier. Virginia Schuett’s PKU News has a good description for explaining the blood-brain barrier’s role in why some PKU patients are less affected by high-phe levels than others.

“There is the occasional individual with PKU, who despite poor control of the diet and chronic marked elevations of blood phe seems to escape any significant neurological impairment. It is suspected that such individuals may be protected at the level of the “blood-brain barrier.” The blood-brain barrier serves to protect the brain from exposure to potentially toxic chemicals in the bloodstream.”

Although I cannot confirm that the blood-brain barrier mutation is what the folks at the Resilience Project are specifically studying with regard to PKU, I would not be surprised if it was at least on their radar.

The Resilience Project defines an “unexpected hero” as someone who “has reached the age of 40–by which time a genetic disease known to emerge in childhood should have manifested–but who does not bear the symptoms of disease.” I’m not yet 40, but I’m seriously considering trying to participate in the project nonetheless.

What are your thoughts on the matter? Would you willingly participate given the chance of new treatments or even a cure for PKU? Or does the thought of submitting your DNA have your internal privacy alarms sounding off? Either way, I’d be interested in hearing your thoughts. And if anyone from the PKU medical community is reading this post, please also chime in!


P.S. The 2008 PKU News article referenced above discussed the blood-brain barrier in the context of an emerging therapy called Large Neutral Amino Acids, or LNAAs. The 2014 National PKU Alliance Conference in Salt Lake City July 10-13 includes a session presented by Dr. Eddy A. van der Zee from the University of Groningen who has received a NPKUA research grant to study LNAA Supplementation in PKU Mice.


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Finding PKU Inspiration at the Gym

Of all places to find philosophical inspiration for living with PKU, I came across this profound quote while visiting my local gym the other day.

Click on image to enlarge.

Click on image to enlarge.

Charles Swindoll, the author of this quote, is an evangelical pastor who I had never heard of prior to seeing this quote and subsequently Googling his name. Clearly, the owner of my gym was trying to speak to the mental strength it takes to improve one’s physique, but anyone who reads this passage will likely apply it to their own personal situation.

As such, when I read this quote, I immediately think about my struggle to start a family. Growing up with PKU, I’ve always felt – even at a very young age – that successfully having children would be THE biggest accomplishment of my life. That is because I have always had a keen understanding of the great effort and sacrifice it would take to return to a restricted diet. I knew that mental toughness and fortitude would be paramount for getting me through. Yet it wasn’t until recently that I realized a host of external factors – items beyond my control – could also sabotage the success I so greatly desired.

I started to feel that despite any level of confidence I had in my own ability to stay on-diet, I could not embark in a high-risk pregnancy without a top-notch team. I found that some of the same support systems that were put in place to aid in my PKU care were also some of my biggest hurdles. For example, my husband and I were told we should “seriously consider adoption,” because birth defects were pretty much guaranteed. And on a separate occasion, after being accused of “cheating” on my blood work, I  realized some professionals would rather point the finger than consider the possibility that process improvements might be necessary. Clearly, I am having difficulty trusting the experts I will undoubtedly rely on most during a high-risk pregnancy. I’ve struggled with this reality for some time now…even placed a moratorium of sorts on any deliberate move I might make towards returning to a controlled PKU diet. Reading this quote at the gym though has led me to think about my situation with a little more optimism. Rather than saying, “I don’t know where to go from here,” I’m now in the position to say “okay (*deep breath*), let’s think rationally and clearly about our options…there has to be another way.”

Perhaps I need to redefine what I mean by “successfully having children.” Even though the suggestion cut deep on an emotional level, maybe I do need to take a second look at adoption or foster care. Does it matter to me and my husband that our children be a reflection of who we are genetically, or can we learn to love another child who is in need a good home? Or maybe thinking rationally means recognizing that we’ll become parents when the time is right. Even when it seems co-workers, friends and family members are all starting families, perhaps our turn is just around the corner…when some other opportunity arises.

Reading Swindoll’s quote hasn’t exactly changed my life or provided me with all the answers, but it does help put things into perspective. I’m not going to settle for a less-than-desirable situation or passively accept the way things are. Instead, I must use my drive…my attitude…to find another way.



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Placebo study could impact PKU clinical drug trials

Findings from a study published in the Oct. 23 edition of PLOS ONE, a peer-reviewed online scientific journal, suggests that people with a gene variation that leads to higher dopamine levels in the brain respond better to placebos than those individuals with low dopamine levels.

The science, health and technology news website LiveScience reported on the study and described how researchers tested to see whether a person’s genes can control a placebo response:

PKU, Phenylketonuria, Gene Mutation, Gene Variance, PKU Clinical Trials, Placebo

“To find out, Hall and her colleagues analyzed DNA from 104 patients with irritable bowel syndrome who were randomized to one of three groups: One was told they were on the waiting list for treatment, another received a placebo in the form of seemingly real, curt acupuncture, and the third group received fake acupuncture from a caring, warm practitioner who looked patients in the eye, asked about their progress, and even touched them lightly, Hall told LiveScience.

Patients with the high-dopamine version of the gene felt slightly better after seeing the curt, all-business health-care provider that gave placebo acupuncture. But they were six times as likely to say their symptoms improved with a caring practitioner as those with the low-dopamine gene, who didn’t improve much in any group.

The findings suggest that medical studies called clinical trials could identify treatment versus placebo effect by grouping patients by gene variant, Hall said. Knowing up front the level of placebo effect for a clinical trial could reduce the cost of the trial significantly by using fewer participants, for instance, she said.”

How does this relate to PKU?

PKU patients have very little or no phenylalanine hydroxylase (PAH), an enzyme in the body that converts phenylalanine into tyrosine. Tyrosine is used by the brain to synthesize dopamine, an important neurotransmitter involved in motor functions and mood. This means that PKU patients, especially those “off-diet” or those not regularly consuming formula, will experience relatively low levels of dopamine. This is the reason that some of the side effects experienced by PKU patients on an uncontrolled diet can include anxiety, depression and other mood disorders.

No doubt, it will be interesting to see whether these new findings will have any impact on how BioMarin or other pharmaceutical companies will structure future PKU clinical trials. Researchers will have to consider whether having a mixture of on-diet and off-diet PKU patients randomly assigned to control and experimental groups will have any bearing on the trial’s accuracy. Or perhaps a closer look at the specific gene mutation that allows some individuals to operate with higher dopamine levels will someday provide answers for how to increase dopamine in those of us who could benefit from a little more.


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Graduation Means More Than a Degree to a PKU Patient

Nicole Merrifield Masters Graduation

My mom and I take a moment before the University of Tennessee master’s hooding ceremony to pose for a quick picture.

I have accomplished something I am very proud of—I received my Master’s of Science in communication and information from the University of Tennessee with a 4.0 grade point average!! It was an effort I initiated over three and a half years ago and one that involved tackling the curriculum one course per semester since I still worked full-time as a communications and marketing specialist. Not only did this require a long-term commitment from both me and the family members who supported me, but it also involved many long nights reading or writing a paper when I had just spent the entire workday drafting and proofing content for my employer. Talk about brain draining! Nonetheless, I managed the entire academic process (from enrollment to graduation), conducted original research that benefited my profession, and ultimately completed my degree with honors. Despite all this, what is probably most significant is that I achieved this after having been off the PKU low-protein diet for more than 18 years.

When reflecting back on all that was accomplished, what occurs to me is that graduation means more than just a degree—it is a demonstration, though be it an elaborate one, of my ability to engage in executive function.

What is executive function and why does it matter to PKU patients?

Executive function is defined by WebMD as “a set of mental skills that are coordinated in the brain’s frontal lobe” and “work together to help a person achieve goals” such as focus, time management, organization and planning. A person who has a lack of control on the PKU diet, especially those with more severe cases, might experience a breakdown in executive function. As a result, those critical aspects of the diet, such as remembering to do blood levels or making sure you take all of your formula, just don’t get done. To be fair, this absence of executive function does not mean that people with a lack of control on the PKU diet are lazy, but rather it is a symptom of the genetic disorder.

When I think about returning to a low-protein diet, I have often wondered if I would do well or fail miserably. But upon graduating from the University of Tennessee, I can say with certainty that, “yes, I do have the ability to engage in executive function,” and “yes, I am pretty good at focusing on a goal and planning long-term to achieve it.” No doubt, this self-awareness is imperative to my confidence as I continue to work through the notion of returning to the PKU diet in anticipation of a pregnancy. On a larger scale, however, I hope that PKU research continues to look at the variance between patients and ultimately determines why it is that some folks are more affected by high-phe levels than others. Whether it can be attributed to the  effectiveness of a person’s blood-brain barrier or the ability to compensate by using other areas of the brain, perhaps more understanding can be gained by looking at those of us who are off-diet but also still high-functioning.



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Keeping an Off-Diet Food Diary during a PKU Kuvan Responder Trial

Off-Diet PKU Kuvan Responder Trial Food DiaryWhen BioMarin’s Kuvan was approved by the FDA in 2007 as the first prescription drug to treat phenylketonuria (PKU), directions for taking the prescription drug stipulated that a low-protein diet must also be followed. However, when I first discussed a Kuvan responder trial with my clinic in the fall of 2010, I was advised that I could remain on a non-restricted diet as long as I consume close to the same amount of protein each day. I suspect that this relaxation was granted with the understanding that if I do in fact respond to the drug, then lower phe levels are better than completely unbridled protein intake. They key; however, to making sure that you consume roughly the same amount of protein each day means keeping a very detailed food diary.

Initially, I found it tricky to figure out a good method for capturing my daily protein intake. I explored the possibility of using Cambrooke’s DietWell app—a fabulous tool for the PKU community—but the more I experimented with it, the more I realized that the items that are truly high in protein are absent from its database.

So now that I’m nearly a week into my Kuvan responder trial, just how have I managed to keep track of my protein consumption? Well, here are the three “secrets” to my success:

  1. Take advantage of publicly available information—Obviously, checking a food product’s nutrition label is a great place to start when keeping a food diary. Be sure that the first thing you look at is the serving size because many products you buy in the grocery store will contain multiple servings per container. Use a weighted food scale, measuring cups or measuring spoons to gauge you portions. For times when not eating at home, try to plan ahead. Many restaurants list nutritional information on their Websites, have apps you can download to your mobile device or sometimes you can even ask your server for a printed brochure of nutritional information.
  2. Men’s Health—Whether it’s the New York Times Bestselling “Abs Diet” or the popular “Eat this, Not that” series, Men’s Health does an excellent job of providing all the information you ever possibly want on a food item. I especially like their recipes where we can cook healthy, in the comfort of our own home, and know exactly how much protein there is in a serving size. I’m sure other recipes, whether in a magazine or posted on a popular cooking website, will provide the same type of useful information. The Men’s Health product line has worked very well for me though.iPhone notepad app screen shot Kuvan Responder Trial PKU
  3. iPhone Notepad App—Lastly, because I am getting my protein equivalent information from a variety of sources, I decided to use my iPhone’s notepad application to track my meals. Even though this notepad app came standard on my iPhone, it has the mobile convenience of the DietWell app, but the flexibility of a blank page. I’m able to enter whatever food product I ate, total the daily protein amount, and when I’m done, forward the finished document directly to my email.



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