Category Archives: Research

Losing it: Both literally and figuratively over PKU and hair loss

PKU diet, PKU hair loss, hair loss, PKU loss of hairLet’s face it. Losing your hair in your early 30s—for whatever reason—is a scary experience. When mine started falling out in large quantities about two months ago, the coincidental timing with my return to the low-protein PKU diet did not go unnoticed. And while I’d rather deal with this humbling experience in private, I felt this subject warranted some attention especially since I’ve only been able to find bits and pieces of anecdotal evidence of the connection between PKU and hair loss.

So let’s start with what are some common reasons for hair loss:

  • Protein deficiencies
  • Deficiencies in vitamins (e.g. B and C), micro-nutrients (e.g. selenium and iron) and fatty acids
  • Imbalance involving thyroid
  • Autoimmune disease
  • Poor blood flow or poor circulation to the scalp
  • Fluctuating hormones
  • Stress

Here’s what you can do if you determine that one or more of these may be causing your hair loss:

  • Protein deficiencies—As was cited in this 2007 article from National PKU News, if a PKU patient is found to be protein deficient, simply increasing the amount of formula consumed each day could help. Speak with your PKU clinic and ask them to run an albumin blood test to determine if you are protein deficient.
  • Vitamin, micro-nutrient and fatty acid deficiencies—Because the PKU diet is so restrictive, vitamin, micro-nutrient and fatty acid deficiencies are likely culprits. A 2010 article from Karger Publishers titled Nutritional Management of Phenylketonuria notes that “Some AA [amino acid] products are devoid of vitamin and mineral supplements to improve taste and acceptability with the assumption that separate vitamin and mineral supplements will be taken each day,” (p. 62). The article goes on to note that the PKU diet tends to contain more carbohydrates and less fatty acids. To help counteract these deficiencies, you may want to take a daily multivitamin and make an effort to consume more vegetable oils that are rich in linolenic acid such as canola or soybean oil.
  • Autoimmune disease, thyroid, poor blood flow and fluctuating hormones–These conditions may indicate that something is wrong independent from the PKU diet; however, it is not impossible for PKU patients returning to the diet to also experience one or more of these. For example, maternal PKU patients may experience “wonky” hormones during and after pregnancy. In any case, these conditions may require a specialist consultation outside of your PKU clinic.

Through the process of elimination, I’ve been able to rule out most of these in my case. Unfortunately, stress—the last reason cited above—is difficult to manage on the low-protein diet. In this case, there are two types of stress worth distinguishing:

1.)    The mental stress it takes to deal with the complexity of the diet, accessibility issues and societal peer pressure

AND

2.)    The physical stress or toll that it takes on the human body when a person returns to the PKU diet

According to a registered dietician my clinic consulted with, hair loss from the sudden shock of returning to diet (which in my case was “cold turkey”), causes a large percentage of the hair follicles to enter into a resting or dormant phase. The patient doesn’t experience hair loss at that moment, but rather when the hair goes from the sleeping stage back into the growing phase, the new hair comes up and pushes old hair out. So in effect, the hair loss I am seeing now actually happened months ago, presumably when I returned to diet in January of this year.

This theory about the stress a body endures after returning to the PKU diet is simply that…a theory. There is little to no research confirming this theory however plausible it may seem. PKU medical professionals may chose to ignore the matter altogether on the premise that they are there to treat the diet and nothing else. This narrow approach to PKU medical treatment is concerning though, especially when you consider that hair loss may become one of the most difficult barriers to dietary adherence. At least it has been for me. In the interim, until more is known about how to treat or avoid PKU-related hair loss, this scenario may also be another “case-in-point” for the need to supplement PKU dietary care with mental health support.

–NM

Be sure to check out the follow-up post on PKU-related hair loss: Hair loss experienced by PKU patients returning to the low-protein diet is temporary.

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Filed under Maternal PKU, Research

What I learned about PKU from 8 million books

Using digitized books to look at PKU trendsThis post is an adaptation of the “TED Talk,” or a video lecture, that was presented by Harvard University’s Erez Lieberman Aiden and Jean-Baptiste Michel in September 2011 called “What we learned from 5 million books.” Essentially, the two researchers created a tool called the Ngram Viewer, which allowed them to search the millions of books that Google has scanned and made publicly available. The large volume of text—which spans centuries and now includes more than 8 million books and approximately a half trillion words—can provide insights into our world, our history and emerging trends simply based on the popularity of certain words or phrases.

Naturally, I wondered what this nifty tool could tell me about the history of PKU and how its treatment has evolved over the years. Before experimenting, I had to narrow the dates in which I would conduct my search. Google’s digitized books include publications between the years 1800 and 2000. For the purpose of investigating PKU, I selected 1930-2000. To understand why, here’s a brief look at PKU chronology:

  • 1934 – PKU discovered by Norwegian physician Dr. Ashbijorn Folling
  • 1953 – Researchers found that a phenylalanine restricted diet helped to treat PKU patients
  • 1963 – Guthrie Method developed (Bacterial Inhibition Assay)
  • 1965 – Newborn screening initiated in the U.S.
  • 1980s – The gene responsible for phenylalanine hydoxylase production was isolated and since that time over 500 mutations in the gene have been identified

And here are some insights that I gathered:

We can visually see how PKU has prepared the way for newborn screening

Google Ngram, How PKU has prepared the way for newborn screening

Click on graph to see a larger view.

Metabolic disorders were in the English vernacular long before PKU or newborn screening. But we can tell the results of this search correlate with the chronology of PKU. The PKU acronym appears as early as the 1930s—when Folling discovered PKU—but it does not pick up in frequency until the Guthrie test was created in the 1960s. Almost immediately or soon thereafter, the concept of newborn screening takes off. We now know that the Guthrie test, which was originally developed to screen for PKU at birth, has led to newborn screening tests for more than 40 developmental, genetic and metabolic disorders.

PKU is most commonly described as a disease

Google Ngram, PKU is most commonly described as a disease

Click on graph to see a larger view.

One of the cool features of the Google Ngram Viewer is that you can use the characters “=>” to determine what words are used to modify other words or phrases. For this particular search, I wanted to see what adjectives were used to describe PKU. Was it disease, disorder or syndrome? As you can see here, disease is the most common descriptor for PKU while syndrome is the least frequently used term. Interestingly, disease is also the first descriptor we see in the literature—it appears that old habits are hard to break!

The practice of counting phe has overtaken the practice of counting grams of protein

Google Ngram, Counting phe has overtaken counting grams of protein

Click on graph to see a larger view.

When I was on the PKU diet growing up in Pittsburgh, Penn., my mother counted phe exchanges. When I first considered a return-to-diet not too long ago, I was advised to count grams of protein. However, after speaking to some other women with PKU, I’ve learned that counting milligrams of phe is a more precise way to track protein intake, especially when considering a PKU pregnancy. Given that experience, I wanted to see what published works in the Google library might suggest is most commonly cited. Here you can see that while the use of grams of protein started strong in the 1930s, tracking milligrams of phe has slowly gained popularity and eventually taken the lead. Interestingly, phe exchanges are not mentioned at all.

The word diet is still overwhelming used to describe PKU medical care

Google Ngram, The word diet is still overwhelming used to describe PKU medical care

Click on graph to see a larger view.

For my last Ngram PKU search, I decided to compare the phrases PKU diet and PKU treatment. In the past, some PKU patients have been denied access to medical formula and foods because of the misconception that the PKU diet is cosmetic and for losing weight. Despite that barrier to PKU therapies, there has been little effort to change the language by which we describe medical care for PKU. Perhaps if Google expanded the scanned library of books to include the years beyond 2000, we would start to see a reversal in this trend.

To be fair, there are some limitations to conducting this Ngram PKU experiment. PKU literature is mainly published in research journals rather than actual books and more recent developments like the first FDA-approved prescription drug to treat PKU would not be included within this data. Nonetheless, I couldn’t resist having a look to see what kind of insight this tool might provide.

Have you played with Google Labs’ NGram Viewer? What other PKU trends and phrases do you think would be interesting to search for?

–NM

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Is taking-on maternal PKU a rational decision?

Some blog followers may have noticed that I have taken a short hiatus from posting content. My absence has in large part been attributed to the fact that I spent the latter part of January, all of February and the beginning of March battling for access to my prescribed PKU formula. Despite having insurance coverage, the durable medical equipment company I had worked with for over a year decided they were losing too much money, cited it as a “reimbursement issue,” and claimed that it was perfectly legal to deny me access to the formula. I spent the next days and weeks attempting to liaison between my employer, my health insurance provider, the formula manufacturer and alternate DME companies. I embarked on an extensive letter-writing campaign and spent many weeks living day-to-day, wondering where my next supply of formula would come from, whether I needed to leave work early to pick up an emergency supply from my local clinic, and so forth.

I go into all of this to belabor my next point, something that has been weighing heavily on my mind: Will I ever feel confident enough to take the next step and transition my “return to diet” into a “preconception diet?” After being off diet for nearly 19 years, I recently returned to the low-protein diet and have been working hard to adhere to its limitations for nearly three months now. For some clinics, that is long enough before women with PKU can conceive. Other clinics recommend six months, but whether the recommendation is three months, six months or an entire year, I do not know that the uncertainty surrounding treatment for maternal PKU will ever improve.

Newborn screening 50 years later: Access issues faced by adults with PKU, Genetics in Medicine, 2013Two recent, yet very different, pieces of literature caught my attention and magnified this dilemma further. The first, which was passed along to me by another PKU advocate Kevin Alexander, is a peer-reviewed, academic journal called Genetics in Medicine. Published by the American College of Medical Genetics and Genomics, the March 2013 issue reviewed the 50th anniversary of the U.S. newborn screening program and looked at the barriers that still prevent access to PKU treatment five decades later. Many barriers were examined including the limited number of adult clinics; the lack of third-party payer coverage; transportation-related issues; and perhaps one of the most commonly ignored barriers, social and mental health support.

Factors identified as affecting access to treatment for phenylketonuria. Source: Newborn screening 50 years later: Access issues faced by adults with PKU, Genetics in Medicine, 2013.

Factors identified as affecting access to treatment for phenylketonuria. Source: Newborn screening 50 years later: Access issues faced by adults with PKU, Genetics in Medicine, 2013, doi:10.1038/gim.2013.10.

The second piece of literature – a blog post by National Public Radio titled “Is having a child a rational decision” – is obviously a much less formal form of literature; however, from a philosophical perspective it examines the reasons why people decide to start a family. The post goes on to say, “Most people don’t decide to start a family after logical and ethical debate; they’re moved (says Belkin): To create a family. To craft a whole greater than yourself, of which you will eternally be a part. To take part in a life from its start to your own finish.”

I guarantee that I am not the only woman with PKU who does feel so moved, to have a part in creating a whole greater than oneself. Unfortunately, women with PKU do not fall within the category of “most people.” The very personal decision of whether or not a woman with PKU will attempt a pregnancy does in fact involve logic and debate. I have experienced many debates…sometimes with friends and family and other times with my self-consciousness. Is a PKU pregnancy is a wise decision, especially given all the unknowns that are seemingly beyond my control?

As a good PKU friend of mine in New York once told me, there are no happy accidents when it comes to maternal PKU. The demands that maternal PKU places on a woman are great indeed. The decision is big. The hurdles along the way will at times seem insurmountable.

Given the current state of the healthcare system and all the barriers that still exist, one almost has to be irrational to finally take the plunge.

–NM

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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.

–NM

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Caring for Maternal PKU: Part III

Welcome to the third and final post in the Caring for Maternal PKU series. In Part I, readers were introduced to the research Kimberly R. Regis RN, MS, CPNP, conducted in support of her Doctorate of Nursing Practice final project at The Ohio State University. The objective of Regis’ research was to “describe the care needs and preferences of adult women of childbearing-age with PKU” by going directly to the women and asking about their experiences. In Part II of the series, we learned that despite being well-informed about the risks associated with maternal PKU, the group of women Regis interviewed had a relatively low combined pregnancy success rate. In an effort to see what factors—in addition to knowledge level—might be at play, Regis explored maternal PKU support systems by asking her participants the following questions:

  • What support systems do participants have that either help or hinder adherence to dietary management?
  • From the participants’ perspectives, what can be done to improve support for ongoing dietary management within the clinic service?

Maternal PKU, Pregnancy and PKU, PKU, PhenylketonuriaFor all of the women who participated in Regis’ study, family members were identified as being the greatest source of support. Mothers in particular were mentioned not only as a supporter but also as an individual who truly understood and empathized with what it was like to struggle with the low-protein diet. Other examples of how family members provided support included finding new recipes to cook or share with the PKU patient, or even in some cases, helping to pay for costly medical foods.

With regard to the support participants received from clinics, most felt that clinicians were friendly and supportive, but some concerns still existed. For example, some participants felt like information about new foods and treatment was only provided if the patient asked about it. Clinic staff did not always provide individualized advice and overall communication from the clinic occurred less frequently overtime.

Right now I’m still just in the monthly stages of taking my level every month, and that’s pretty much all that I hear from my nurse. And I never really hear from my dietician other than when I call her to order formula.”

The reality is that most PKU clinics are spread-thin and overworked because of having to respond to more than just PKU patients. But developing specialized care for maternal PKU is significantly more complicated than just refreshing clinical best practices. That’s because as Regis acknowledged, treatment for PKU has evolved over the years, allowing for more PKU patients to live longer and engage in “traditional” lifestyle activities such as pursuing advanced college degrees and starting families. Unfortunately, despite the need for individualized care, many PKU adults are still seeking treatment at a pediatric-focused facility such as Children’s Hospital. To be fair, participants within Regis’ study did not explicitly express concerns about receiving care from a pediatric institution; however, there was strong agreement on the need for more support beyond education.

What would this additional support look like? Regis suggests that social work, mental health and gynecological services may all be applicable for advancing the care of maternal PKU. No matter what the medical treatment of PKU will look like in the years to come, it must evolve to include geneticists, dieticians and nursing practitioners who understand and specialize in maternal PKU. Perhaps Regis herself said it best when she recognized women of childbearing age with PKU as being a “distinct population with the shared risk of having offspring with disabilities as a result of their genetic disorder.”

A distinct population – even one that is a subset of a group defined by a rare genetic disorder – should translate into individual, specialized care.

–NM

Caring for Maternal PKU: Part I

Caring for Maternal PKU: Part II

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Caring for Maternal PKU: Part II

Maternal PKU, Phenylketonuria, Maternal PKU Knowledge Test

For the second installment in the Caring for Maternal PKU series, let’s take a closer look at the knowledge factors incorporated into the participant interviewee questions for Kimberly R. Regis’ Doctor of Nursing Practice final project, Childbearing age women with PKU: Assessment of care needs and preferences. In Part I of the series, questions four and five asked:

4. What is the knowledge level of the participants regarding PKU and maternal PKU?

5. How does knowledge level regarding PKU impact decisions regarding birth-control and family planning?

Why would Regis focus on the knowledge level of the adult women with PKU? For the last two decades, PKU research has focused in large part on emphasizing the need to educate adult women with PKU so they could better self-manage their condition and prevent the occurrence of maternal PKU syndrome. Regis wanted to “gain a better understanding of the ways in which a children’s hospital-based metabolic specialty clinic may best serve them [adult PKU women of childbearing age].” Was the answer that clinics should continue to serve maternal PKU patients by following conventional research, which emphasized the importance of ongoing education? Or was there a need for something more?

To explore these options, Regis started with the knowledge variable and had the six participants take the Maternal PKU Knowledge Test, a 10-question quiz that was developed in 1990 by Shiloh, St. James and Waisbren. The three authors recommended the test as a way for clinics to screen and identify adult women with PKU who might benefit from more education.

The study’s participants answered a majority of the questions correctly, with scores ranging from seven to 10 correct. The question that elicited the most trouble when trying to answer was number seven (you can see a complete list of questions and take the test for yourself by visiting the Maternal PKU Knowledge Test page on PKU Parlor). A common theme that emerged from the open-ended questions was that participants felt they received vague and oversimplified information, which lacked details for explaining the science behind why a developing fetus could be harmed by poor dietary control. One participant stated she had never been taught about maternal PKU saying, “I don’t even remember having the conversation.”

With regard to how the participants’ knowledge level may have impacted their family planning decisions, all of the participants reported that PKU strongly influenced their decision about whether or not to have children. Regis noted that one participant commented that she was afraid to have children because of the possible outcomes, while another participant who originally wanted a large family said that concerns over the PKU diet changed the number of children they would ultimately plan for.

“I never thought growing up that I could never had kids. I always had the big family in my head—five kids, four kids.”

Observations within the study also revealed that even though there were 12 pregnancies among the six participants, only four resulted in live births. So one begs to ask the question: If these six women were relatively well-informed about the risks associated with maternal PKU…AND if knowledge of those risks, as well as ways to minimize those risks, impacted the decisions these women made with regard to family planning, then what else could be the reason behind such a low pregnancy success rate?

Stay tuned for the concluding post in this three-part series on Caring for Maternal PKU. Assuming that education alone may not be enough to improve pregnancy success rates among adult PKU women, Part III will take a look at the support systems available to the participants in Regis’ study.

–NM

Caring for Maternal PKU: Part I

Caring for Maternal PKU: Part III

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Caring for Maternal PKU: Part I

I recently came across a research paper written in 2011 by Kimberly R. Regis RN, MS, CPNP, and titled Childbearing age women with PKU: Assessment of care needs and preferences. As the final project for her Doctor of Nursing Practice at The Ohio State University, Regis used open-ended questions to gather insight on any concerns adult women with PKU may have as far as managing their condition and the impact those concerns may have on family planning decisions. Being a childbearing-aged woman with PKU, I must say that I truly identified with many of the observations documented in her research. This blog post is the first in a three-part series devoted to maternal PKU and the findings outlined in Regis’ research.

Nationwide Children’s Hospital Regional Genetics Center in Columbus, Ohio, PKU, PhenylketonuriaFor the purpose of this first entry, let me simply set the stage. Regis conducted telephone interviews with six different adult women who were PKU patients at Nationwide Children’s Hospital Regional Genetics Center in Columbus, Ohio. Though a small sample size, the participants were Caucasian, between the ages of 19 and 35, and had varying levels of protein intake. All but one of the participants was on formula and the most recent set of phe levels for the group ranged between 2.6 mg/dl and 19.9 mg/dl. Most shockingly though was that even with a combined total of 12 pregnancies among the six participants, only four resulted in live births.

Clearly, even with a small sample, this ratio is unacceptable…and, if one dares to make the leap, these figures could represent an issue much larger than just dietary adherence. This is the crutch of Regis’ research as she dug deeper under the complex layers of the genetic disorder and asked what exactly are the factors impeding these women from reaching dietary compliance. To help identify these factors, Regis asked participants the following six questions:

  1. How does PKU influence daily life?
  2. What strategies are used for dietary management?
  3. What support systems do participants have that either help or hinder adherence to dietary management?
  4. What is the knowledge level of the participants regarding PKU and maternal PKU?
  5. How does knowledge level regarding PKU impact decisions regarding birth-control and family planning?
  6. From the participants’ perspectives, what can be done to improve support for ongoing dietary management within the clinic service?

Those readers familiar with my blog know that maternal PKU is the primary reason for why I created PKU Parlor. As I contemplate a return to diet and eventual pregnancy, I am deeply concerned about the odds I’m facing and cannot help but empathize with the PKU women who are profiled in Regis’ study. I ask myself, “will I face miscarriage after miscarriage, or will I have a baby born with severe mental disabilities or congenital heart failure?” Just maybe I’ll be one of the fortunate ones who successfully return to diet and have a normal, healthy baby.  With all of this in mind, I’ll spend the next two posts in this series taking a closer look at the knowledge and support factors outlined in questions three through six listed above. I hope you will check back for more of this series and please comment in the field below to join-in on the conversation.

–NM

Caring for Maternal PKU: Part II

Caring for Maternal PKU: Part III

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