One of our Keynote Speakers, Randy C. Eisensmith, is an Associate Professor at the Institute of Gene Therapy and Molecular Medicine and Department of Human Genetics at Mount Sinai School of Medicine. His current professional projects are the Development of Gene Transfer Vectors, Gene Therapy for Phenylketonuria, Gene Therapy for Hemophilia, and Gene Therapy for Diabetes.

Dr. Randy Eisensmith was met with a warm
welcome on Saturday November 11th at Children's Memorial Hospital for
the 31st PKU Annual Meeting. Dr. Eisensmith's affable manner and
genuine interest in the day's events was apparent from the moment he
stepped on to the stage. He began with a brief introduction and moved
directly on to a "Genetics 101" session. He reviewed basic cell theory
and discussed the Human Genome project. He talked about the functional
and structural elements of protein. He described how DNA mutations alter
protein structure. He reviewed the discovery of PKU and how the presence
of phenylketones in the urine led to the ability to test for PKU. He
also reviewed how PKU is inherited as a recessive genetic trait.

Dr. Eisensmith shared with us the 7 Goals of the Molecular Genetic Study
of PKU:
1. Gene Isolation and Characterization
2. Chromosomal Assignment of Disease Locus
3. Linkage-based diagnostic tests
4. Mutation Analysis
5. Genotype/Phenotype Correlations
6. Population Genetics
7. Somatic Gene Therapy

He told us about how in 99% of the families who learn they have a child
with PKU, that child is the first occurrence and the family's first
exposure to PKU. He remarked about how one does not often hear a
relative say something like, "Oh yes, PKU, Aunt Phoebe and Uncle Charlie
had PKU, don't you remember dear?". He went on to explain that different
mutations have different effects and the result is that different
patients tolerate different amounts of PHE. He described a study which
found that patients with Classic PKU are different than those with mild
PKU due to differences in liver enzymatic activity. Those with Classic
PKU typically have 5% or less of normal enzyme activity in their liver;
those with Mild PKU have 5-25% of normal enzymatic activity; and those
with HyperPhe have 25-50% of normal enzyme activity in the liver. PKU is
only apparent when the percentage of enzyme activity falls below a
certain threshold. As a result there is a correlation between genotype
and phenotype (type of PKU).

The utility of this type of information is to diagnose the type of PKU
and provide nutritional analysis and guidance for patients. This helps
determine the probable outcome of treatment and allows for less guessing
in the early stages of life. Dr. Eisensmith also discussed the
frequency of certain mutation types in Europe. He provided interesting
data about anthropology and showed how the settlement of certain
geographic areas had a direct impact on how PKU was spread.

Dr. Eisensmith moved on to discuss Gene Therapy. He told us what we
already know which is that because PKU has a small impact on the public
health it will likely receive only the incremental benefit of Gene
Therapy Research. He discussed how the rejection of the corrected gene
is an issue in gene therapy. Reaching the nucleus of the targeted cell
is the key.

Gene therapy will be successful when it is:
Easy & Cheap
Can be Administered Cheaply
Has a Good Result
Reaches the Targeted Gene
Transfers Easily
Has Persistent Expression
Allows for Regulated Expression.

The types of Vectors used in Gene Therapy are (A) Non-Viral: Naked DNA;
DNA Liposome; DNA Protein or (B) Viral: Remove damaging part of the
Virus and insert the "good" gene.

As an aside Dr. Eisensmith mentioned that Tyrosine is the first
ingredient needed for pigment and therefore people with PKU can have
lighter skin, hair and eyes than those without PKU. Once those with PKU
are on diet normal pigmentation can return. He shared anecdotal evidence
that Asians who were born very light (with blonde hair) can become
darker once effective treatment is received.

Dr. Eisensmith informed us that a realistic goal is to restore 15-20% of
normal liver enzyme activity but even 3-5% can make a difference in what
a person can eat. The bad news is that recent animal research has shown
that after 3 weeks of improved activity enzyme activity dropped back to
the pre-treatment level. Animals experienced an immune response and
therefore subsequent treatments were less effective. Researchers will
need to depress the response of the immune system to prevent rejection
of the gene therapy drug. The solution is to modify the virus to be
non-immunogenic (meaning no adverse immune system response). The drugs
can be engineered to reduce immune reactions and allow persistent
expression of the therapy over time. An alternative is to treat
recipients of gene therapy treatment like transplant patients and
provide drugs to reduce the immune system's response to prevent
rejection.

At the current time there are different types of possible gene therapy
drugs but the problems are (1) Immune System response; and (2) drugs
which last but do not provide a complete cure. Researchers are working
on a convergence of types of drugs to improve expression and duration of
successful enzyme activity.

Dr. Eisensmith reminded us that while he has lots of encouraging news,
the road to a gene therapy cure for PKU is not an easy one. While
researchers continue to work on the matter, resources will be focused on
more life-threatening conditions such as cystic fibrosis or diabetes.
In addition, while there are promising potential solutions to current
hurdles in PKU Gene Therapy treatments, but these treatments must be
transferred into treatments suitable for humans.

Dr. Eisensmith concluded his talk by thanking the PKU Organization of
Illinois for inviting him to our meeting and to wish us good luck in our
continuing endeavors. On behalf of the entire Organization we would
like to thank Dr. Eisensmith for traveling to Chicago to speak to us and
for bringing us up to date on the current progress of Gene Therapy
Research for PKU. The Board will continue to keep in touch with Dr.
Eisensmith and will update you on developments in PKU Gene Therapy as we
hear about them.

Dr. Koch’s Keynote Presentation

THE PKU CONSENSUS STATEMENT

In 1977, the National Institutes of Health (NIH) launched a program which was designed to improve the lines of communication between health researchers and practicing professionals. The answer to this was the consensus development whose objective was to provide the physician and the public with current, responsible information on the pros and cons of medical technologies.

In Illinois, PKU has been part of newborn screening since 1965. During the past 35 years, many advances have been made in the treatment of PKU. However, there was still some discrepancy between the U.S. clinics in regards to how PKU should be treated. Therefore, it was concluded that a Consensus Statement was needed for PKU. For one year prior to the Consensus meeting, a nonadvocate, non-Federal panel of experts researched and studied PKU. Between Oct. 16-18, 2000, many experts in PKU and families met with this panel. During the meeting, the PKU experts from around the world had the opportunity to present their experiences and feelings about PKU and its treatment. After 1 ½ days of presentations, the NIH panel drew up the following conclusions about the treatment of PKU:

1) Hospitals should obtain and send the samples for newborn screen at 24 hours after birth and any positive results should be reported within 7 to 10 days of birth so treatment can be initiated as early as possible

2) Metabolic control of PKU is necessary over the lifespan; therefore, diet is recommended for life

3) Recommended treatment Phe levels: 2 to 6 mg% (121 to 364 umol/L) in infants through 12 years; 2 to15 mg% (121 to 909 umol/L) in children over age 12 years. Below 6 mg% (364 umol/L) prior to and during pregnancy. It is recommended that plasma phenylalanine levels be below 6 mg% (364 umol/L) for 3 months prior to conception

4) Suggested guidelines for monitoring plasma phenylalanine levels are: Once a week during the first year of life Twice a month between ages 12 months and 12 years Once a month in individuals who are over 12 years Twice a week during pregnancy of a woman with PKU

5) The treatment of PKU requires a comprehensive, multidisciplinary approach including physician and dietitian

6) Equal access to culturally sensitive, age appropriate treatment programs for all individuals with PKU

7) Continued research into the pathophysiology of PKU

8) Uniform policies so there are no financial barriers to the acquisition of the medical foods and the special low protein foods. Also, that support services that are necessary to achieve metabolic control are easily accessible

9) Research on non-dietary alternatives was strongly encouraged.

10) DNA mutation analysis and genotype determination should be performed on each individual diagnosed with PKU for genetic and management counseling, follow-up and long-term prognosis.

At the recent PKU Annual Parent Meeting, there was agreement between the Chicago PKU clinics that the guidelines are appropriate. And, that the clinics have been operating in a manner consistent with the guidelines. It is also important to note that these guidelines may not apply to all situations. The physician/clinic may need to adjust the treatment of individuals as needed.

It is hoped that the consensus statement can facilitate improved care and encourage further research in PKU. If you would like to read the entire consensus statement, you can visit the website: http://consensus.nih.gov.

2000 Family Camp

The following PKU Family Camp summary was written by a mother from Michigan. She wrote it to the PKU Listserv the day after the end of camp. We got her permission to reprint it here, and felt that it described this year’s camp much better than any of us could have done.

Hello Everyone,

Last evening my son, and I along with our very good friends,  returned home from our first experience at the PKU Camp in Illinois hosted by the Illinois PKU Parent Group. To say we had an incredibly fun time is simply....... well .....an understatement.

I would first like to thank the parents on the board and all the families from the state of Illinois that made us feel so welcomed. It was very evident how much thought and care went into the planning of the weekend. I'm still so impressed at how much fun was packed into two days.... yet it was so relaxing!!

The drive to the camp was about 5 1/2 hours.....and it was worth every mile I might add. We arrived Friday and stayed in a hotel close by so we would be rested for the first day of camp on Saturday. We arrived at the camp around 10:00am the next morning and got settled into our cabin. It was really fun to "rough" it for the weekend. Not being a camper myself I was impressed with the cabins....they offered everything you would need. 

The first thing I noticed were kids walking around drinking their milk. I knew right then this was going to be an experience that only families living with PKU could truly appreciate. While the kids were out playing and getting acquainted with one another the parents were putting all the low protein foods away and getting the milk in the fridge. It was interesting to see how much we had in common without having ever met each other. I also thought it was wonderful to hear muy son asking the kids questions like...."Do you have PKU? Does your mommy poke you on Sundays? Do you drink your milk?" And yet....after these questions were resolved in his mind the PKU became a non-issue. It was then just a bunch of great kids getting together to have a great time!!

At noon the fun began. We hiked over a river and through the woods (seriously...we did....and no.... Little Red Riding Hood wasn't with us HA! ) on a beautiful trail to have lunch in the cafeteria. We went through the line and they had low and high phe spaghetti. It was so neat and odd to be able to go to a meal without having to bring along my son's food cooler.

This was my first experience of not having to worry about his menu for trip and I was a little hesitant. But I got used to it very quickly. And I also quickly realized I was not going to need the huge box of food I packed ..... just to be safe. Between our two families we could have fed our kids for a week with the food we brought..."just to be safe". We truly only needed the scale and milk.

After lunch we went back to the camp grounds and got ready for an hour of pool fun. The kids had a blast swimming and it was a great time to talk to some of the parents and get to know them a bit. After swimming we got changed and went for fun with arts and crafts. The kids made scarecrows, witches, painted pumpkins and gifts bags......lots of fun things. While they were working on their crafts hay rides were going on. They had several trips so everyone had a chance to work on crafts as long as they wanted and fit in the fun ride. OH... I almost forgot.....before the arts and craft fun started the kids lined up to have a chance to crack open the piñata. All had a great time swinging the bat but gathering the candy was the most exciting......well not more exciting then eating it!! And yes...the candy was all pku appropriate!

Just when you thought there couldn't be anymore fun in one day we realized there was still much more to come. Around 6:00 pm we had dinner. Pizza was ordered in for the non-pku campers and a large table of yummy pku pizza was set up for all the pku campers. Everything looked so wonderful. In addition to that there was a low-phe table that was set up all the time with tons of yummy low-phe snacks for the kids to munch on at their convenience. There was everything from cookies to muffins to veggie stix to low-phe ice cream. The variety was just incredible. After dinner we were surprised with a visit from a clown who did wild magic tricks. And while the kids watched the show they were treated to cotton candy made right there by a cotton candy machine that was brought in especially for them.....that was great!! Each kid even got a balloon made into the toy/animal of their choice. 

After the show we all went outside to enjoy the blazing campfire. Everyone had fun roasting marshmallows and eating smore's. The sky was so clear and beautiful that night that some of us even took a little walk to a big open field and laid on the ground enjoying the beautiful picture of stars from above. At 10:00 pm everyone went to their cabins, tents or campers to hit the sack. Although the day was jam packed with activities it was incredible how smooth everything went. I've never done so much in one day and still felt so relaxed. A true testament to great organization!!

The next morning we all gathered for another great breakfast. Once again, the variety for the kids was incredible. They had everything to select from.....they definitely ate well!! After breakfast we all headed to the big open field and spent the morning playing a ton of fun games. The kids were having so much fun it was sad to think that we would have to leave that day. After the fun and games we all gathered for a group picture, ate brunch....(yes more yummy food) and packed up to go home. I think it would have been nice to have the camp start on Friday. It seems the kids were just getting comfortable by Sunday morning and one more day would have really topped it off. However, that would really require alot more on the individuals organizing it so the two day theory does make sense.

I can't thank the PKU Parent Group of Illinois enough for making this opportunity possible for us. We created so many fun memories that will last a lifetime!! It was definitely a weekend we will never forget!! I HIGHLY recommend any family that has thought about attending this camp but just hasn't been sure to JUST DO IT!! You won't be disappointed!

Finally, as we were getting things packed into the car I asked my son..."Well, did you have a fun weekend?" He answered with a big smile on his face.."Yes...this was the best fun I ever had". At that moment my eyes filled with tears and I we gave each other the biggest hug. I felt such joy inside and I knew this was one trip we would be making again and again!!

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Last modified: April 05, 2001