Immanuel-Kant-Gymnasium Münster-Hiltrup
Year 2008/09
GK Biology bilingual 12.2 (Mrs. Ruwe)
Life With PKU – A Case Study
Term Paper
by
Anika Zäpernick
Münster
March 2009
Acknowledgment
To the family J., without whose willing help and honesty,
this paper would have never been written.
2
List of Contents
1
Preface………………………………………………………………………...4
2
Phenylketonuria……………………………………………………………...5
2.1
Discovery of phenylketonuria………………………………………………....5
2.2
Genetics…………………………………………………………………….….6
2.3
Visual nature……………………………………………………………….…..7
2.4
Occurrence…………………………………………………………….……….7
2.5
Screening………………………………………………………………………8
2.6
Treatment………………………………………………………………………8
2.6.1
Diet……………………………………………………………………….……8
2.6.2 Amino acid mixture……………………………………………………………9
2.6.3
Kuvan - An other way of treatment?..................................................................9
2.7
Maternal phenylketonuria (MPKU)……………………………..……………10
3
Life with Phenylketonuria – A case study…………………………………10
3.1
Introduction……………………………………………………………….…..10
3.2
Diagnosis………………………………………………………………..…….11
3.3
Diet - Learning by doing……………………………………………………...11
3.4
Amino acid mixture – drink or tablets………………………………………..12
3.5
Problems because of PKU………………………………………………….…12
3.6
School - job – future………………………………………..……………....…13
4
Conclusion…………………………………………………….…..……….…14
Bibliography………………………………………………………………………….15
Attachment...................................................................................................................16
3
1
Preface
The story, how I had the idea of writing my term paper on Phenylketonuria (PKU) is a
very simple one. I actually already had a topic for my term paper, but I wasn’t satisfied
with it. One day, however, my mom gave me a book to look at. It was a recipe book for
people with PKU. I knew at once, that that was the topic I had been waiting for. I was
anxious to find out more about the disease, that I had never heard about before. My
mom told me, that the woman, who wrote the recipe book, has a son, who is affected by
PKU. In that account, I kept wondering about how this boy’s life differs from mine, if
he has to face many problems in his daily life and how normal his life can be in the first
place.
PKU is the most common hereditary metabolic disease. Affected people are not able to
break down (metabolise) the amino acid phenylalanine (phe), which then accumulates in
the body and causes severe damage, especially in the growing organism of a child.
My mission of this paper is to answer the question, “Is it possible to live a normal life
with PKU?” Apart from that, something else is very important for me, that doesn’t have
anything to do with my main question. This paper should also help making PKU more
known in society, so that people like me, who have never heard of it before, get to know
this disease and will be able to understand it more easily.
The main section of this paper is divided into two main parts. In the first part I
concentrated on the general information of PKU, for example, how PKU was
discovered, the cause of its emerge and how it can be treated. The second main part
shows a case study, which explains the information given in the first part. The reason
why I made use of a case study is the fact that I believe it is much more vivid to explain
how one can life with a disease, when a concrete example is used.
The information for my research were not easy to get. The books I found in various
libraries were not on the latest state of affairs, so they only gave me general information
on PKU. On the internet I also didn’t find the information I needed to answer how one
can live with PKU. For that reason, I got in contact with the woman, who wrote the
recipe book, which gave me the topic for this paper in the first place. She and her family
didn’t only give me books and all the other information I needed for my research, but
also told me the details of their life with PKU.
4
2
Phenylketonuria
2.1
Discovery of phenylketonuria
Not that long ago phenylketonuria (PKU) was unknown. Today, there are normal
children who are successful in school and grow up to normal adults, despite their basic
metabolic disturbance. The discovery of PKU is a very interesting one as to the story of
a very observant Norwegian mother who discovered her two little children mentally
retarded. The two children showed the same symptoms: both seemed normal until a few
months after their birth, when they lost interest in their surroundings. Also after a year a
slowing of their development was noted and they had problems with learning to walk
and talk. The most significant symptom was the musty odor which clung to them from
their early infancy.1 According to the persistent searching for medical advice this
woman came in contact with Asbjörn Fölling, who in 1934 took a closer look at the four
and seven year old children.1
In order to find the reason for this distinct clinical picture Dr. Fölling worked with
complete dedication for the problem. After many tests he to his surprise discovered the
urine to turn green with the addition of ferric chloride. This fact didn’t seem to be
random, so he analyzed the urine to find a connection with the not discovered disease.
Already after five months Dr. Fölling was able to publicize this new metabolic disease,
which he called “imbecilitas phenylpyruvica”. Dr. Fölling had discovered that
phenylpyruvic acid is responsible for the disturbance in the metabolism of the amino
acid, phenylalanine, which is the same irregularity causing the retardation. Due to Dr.
Fölling’s discovery, scientists all over the world became engaged with the disease,
which was later called “Phenylketonuria”.2
1
Cf. Lyman, 1963, p. 3-5
2
ibid. p. 6-7
5
2.2
Genetics
PKU is an autosomal-recessive inherited metabolic disease. The “wrong” genetic
information is passed on by both parents. In the case of the parents a “right” genetic
information covers up the “wrong” one, so that they themselves are not affected by the
disease. They are called „silent carriers“.
“When two carriers conceive a child, there is a one in four (or 25 percent) chance for
each pregnancy that the baby will have PKU (Picture 1). The incidence of carriers in the
general population is approximately one in fifty people, but the chance that two carriers
will mate is only one in 2500.”3
parents
father
mother
children
normal
carrier
PKU
healthy
affected
carrier
-
healthy
healthy
Picture 1: Inheritance of PKU4
The error in the genetic information affects the metabolism of the protein module
phenylalanine, an essential amino acid, which is normally in the liver turned into the
amino acid tyrosine. In the process of biosynthesis the “wrong” amino acid is
assembled, as a result from the mutation. This leads to a missing or lacking activity of
the enzyme which turns phenylalanine into tyrosine. The surplus of phenylalanine
accumulates in blood and tissues and causes a brain damage. In this case a severe
damage in the mental and movement development can already be seen in infancy.5
3
cf. www.pkunews.org (02.03.2009)
self-made
5
cf. Wachtel, 2007, p. XI – XII
4
6
2.3
Visual nature
PKU patients are born as apparently healthy children. Pregnancy and birth as well as the
birth weight statistically doesn’t differ from the norm. The body development is
delayed, but remains otherwise inconspicuous. To the most frequent occurrences counts
the light complexion of the patients. More than 90 percent have blond hair and blue
eyes. The pigment lack is referred to the repressive effect of the phenylalanine on the
oxidation of the tyrosine, through which the creation of melanin is disrupted.6 The skin
of the often handsome seeming PKU patients is normally delicate, soft and sensitive.
About a third comes down with eczema primarily in the face. The musty, as mouse-like
described, odor that surrounds the patients is ascribed to the phenylacetic acid that is
excreted by the sweat.7
If PKU isn’t identified early enough, severe mental disorders can be noticed. In this
case, the affected child doesn’t seem to recognize its surroundings and isn’t able to walk
or talk. It is completely mentally retarded. If, on the other hand, PKU is diagnosed early
enough and the treatment is kept strictly, the symptoms can be improved or even
reversed.
2.4
Occurrence
In earlier days scientists figured that the disease occurs in every part of the world and
doesn’t seem to favour any race in particular.8 But newer researches have found that the
incidence of PKU varies a lot throughout the world. It is interesting to see that “the
incidence in Caucasians is about 1 in 10,000 and 1 in 200,000 in African Americans.
Also, in Chinese, it is 1 in 15,000 but in Japan it is 1 in 100,000. In Turkey, it is 1 in
2500 due to intermarriage. In Ireland it is 1 in 4,000 and in Poland, it is 1 in 7,000.”9 In
the past, when the first statistics were released, a lot of PKU cases were described in
North and Central Europe and North America, which was without a doubt due to the
intensely research made there.10 Moreover, in 1963, 2000 PKU patients were calculated
6
cf. Grüter, 1963, p. 16
ibid. p. 17
8
ibid. p. 11
9
www.pkunews.org (02.03.2009)
10
cf. Grüter, 1963, p. 11
7
7
in Germany, whereas today the numbers lie at 5000 to 6000 people with PKU living in
Germany.11
2.5
Screening
In Germany and many other countries a „Newborn Screening“ for PKU is carried out
within the 3rd to the 5th day of life. Unlike in the early days of research when the urine
was examined, nowadays with the help of a special test procedure the blood gives a fast
diagnosis if the baby is healthy or affected by PKU. In a suspicious case, follow-up
examinations immediately take place, and treatment is instructed.12
2.6
Treatment
2.6.1 Diet
At the beginning of the 50th, the German paediatrician Prof. Dr. Horst Bickel for the
very first time found out that PKU can be treated with a “phenylalanine-reduced diet”.
In his studies, he diagnosed, that in an untreated PKU, the high phe levels are the reason
for the occurring damage. To this, for the paediatrics momentous achievement, an at this
time two-year-old girl had a great impact. Sheila Jones (1949-1999) was the first PKU
affected child that was treated with a phe-reduced diet.13 PKU affected people, as well
as every human being, need protein, fat and carbohydrate. But protein contains
phenylalanine, which bears serious problems for these people. For that reason it is very
much necessary for a PKU affected person to know the protein-concentration in their
food. Fat and carbohydrate on the other hand can be taken in without any limitation.
One differentiates between three groups of food containing different amounts of protein.
In the “Red Group” you can find every food, with a high phe concentration, for example
meat, noodles, milk and milk products. If possible the concerned person resigns from
this food completely.
The “Yellow Group” contains food with a medium phe
concentration, for example potatoes, rice, some vegetables, bananas or cream. In this
case, you have to calculate the phe concentration, to find out how much you are allowed
11
cf. Awiscus, 1998, p. 21
cf. www.dig-pku.de (02.03.2009)
13
cf. Wachtel, 2004, p. 16 – 17
12
8
to eat a day. The food in the “Green Group” doesn’t have to be calculated because it
contains very few or no protein, for example butter, oil, a lot of fruit or jam and nearly
every kind of drink. Furthermore, special products, produced especially for PKU
affected people count in this group. For example, low protein bread, low protein flour or
low protein pasta.
There are so called food composition tables that can help you calculate your daily meal
accurately. This table became necessary, because every now and then, uncertainties with
the calculations occurred in families. This composition table is revised regularly and
accompanied scientifically.14 To calculate your food correctly, it is necessary to know
how much phe your body can tolerate. Because this factor is different in each person,
your individual phe-tolerance has to be determined by a blood test. The phe-tolerance is
the factor that shouldn’t be exceeded or under-run in your daily PKU diet.
2.6.2 Amino acid mixture
Every human being needs a certain amount of protein per day. It is estimated, that a
teenager normally needs about 0.7 to 1.2 grams of proteins per kilogram bodyweight.
As to the phe-reduced diet, a PKU affected person has to observe, a definite amount of
protein is missing in their daily necessity. To satisfy this demand, an amino acid
mixture was developed especially for PKU patients. The daily amino acid demand has
to be taken in, in three to five portions a day with the meals. When the daily dose is
taken in at one time, the amino acids can’t be transformed properly in the body. This
amino acid mixture is not a drug but a protein substitute containing vitamins and
minerals. The costs for the product are covered by the health insurance.15 Due to the
amino acid mixture, the PKU diet becomes a healthy and complete nourishment.
2.6.3 Kuvan - An other way of treatment?
Unlike for diet treatment, where there are nearly 50 years of experience, there is no long
term experience with other ways of treatment, for example for drugs, that lower your
blood phe levels. However, researches have been made and until December 2007 the
new drug named Kuvan was the first treatment besides the PKU diet to be effective.
14
15
Attachment, p. 16
cf. www.comidamed.de (03.03.2009)
9
“Kuvan, produced by Biomarin Pharmaceutical Inc., is a drug that, in some people with
PKU, can enhance enzyme activity and lower blood phe levels. Kuvan is a form of the
cofactor for the phenylalanine hydroxylase enzyme, called tetrahydrobiopterin or BH4.
When given in sufficiently large doses, it can cause whatever residual enzyme activity
exists to work harder and thereby reduce blood phe levels. In rare cases, someone on the
diet has been able to discontinue the diet entirely; but more typically, use of Kuvan has
resulted in greater tolerance for dietary phenylalanine while the diet is still
maintained.”16 Of course, this drug doesn’t work in every person with PKU. That’s why
there still have to be long-term tests made, to find out whether every person with PKU
is responsive to the drug or if there are long term side effects.
2.7
Maternal phenylketonuria (MPKU)
As we already know, it is possible for a person with PKU to live a normal life. Women
however have to deal with a very special situation, which bears some problems.
During a pregnancy, the phe concentration in the mother’s blood always has to be below
5 mg/dl, otherwise the unborn child will be harmed severely. For that reason, a couple
needs to prepare themselves thoroughly for the pregnancy. Before the mother decides to
get a baby, she should make sure, that she is able to control her phe levels extremely
well, because the phe level in the mother’s blood is essential for the health of the child
from the very first day of pregnancy. If the diet is kept under control for the whole
pregnancy, there is a large probability, that the child will be healthy and normal.
3
Life with Phenylketonuria – A case study
3.1
Introduction
At the top of my research, I was very lucky to have the opportunity to talk to a family,
whose child has PKU. Family J. was very nice and invited me over to their house to talk
to me about how they, as a family, and especially how their son manages to live with
PKU.
16
www.pkunews.org (02.03.2009)
10
Jan J. is a normal boy at the age of 18 years. He goes to High School, plays sports, goes
out to party at the weekend and does all the things every other boy at his age normally
does. The only matter that makes him different from other teenagers is when it comes to
his diet.
3.2
Diagnosis
It wasn’t always certain, that Jan would be healthy and normal, as his mother explained
to me. Ten days after their son’s birth, the parents J. got a call from the hospital, that
some of their son’s blood levels were not normal, but the doctor assured them that it
was probable just to be a mistake. The paediatrician unfortunately couldn’t make sense
of these results either, whereas in a different hospital many extensive tests were made
with the little baby as fast as possible. The young mother had to stop breastfeeding, at
once, and the baby’s food was changed to a mixture of glucose, oil, mondamin (starch
flour), amino acid mixture and water. The result of the tests was: their son had
Phenylketonuria. This diagnosis was a great shock for the young family, mostly due to
the fact that they didn’t know much about this very rare disease. After a lot of research,
however, Mr. and Mrs. J. knew that their son wouldn’t die and that, with the help of the
right treatment, it was possible for him to live a normal life.
3.3
Diet - Learning by doing
Thereupon, parents J. did everything to educate themselves with the topic of PKU.
Naturally, from the moment when the diagnosis became clear, the most important thing
in their lives was their son’s health. If they didn’t calculate his food right, or didn’t pay
attention to what he was eating, it would have had bad consequences for the small child.
As he was growing up, Mrs. J told me, Jan already had to help his mom cook and learn
what he was allowed to eat at an early age.17 For Mrs. J. it was important, that Jan was
prepared for the future, when his parents are not going to be there to make him food.
For this purpose, the family tried different ways for all of them to learn what it was to
observe. They showed me for example a game, manufactured especially for PKU
children. In this game, the cards showed in which phe-group a kind of food belongs, so
17
Attachment, p. 17
11
there were red, yellow and green cards. It was very interesting for me to see how much
food contained a lot of phe, which I didn’t even expect there. To make this clear to
myself, I put cards showing food with a lot phe and cards showing food with reduced
phe, next to each other.18
Today, Jan knows the phe concentration of nearly every food and only rarely needs to
look up a phe level in his food composition table to know how much he is allowed to
eat a day.
3.4
Amino acid mixture - drink or tablets19
To cover his daily demand of protein, Jan has to take in all the amino acids that he
doesn’t get through his diet. Therefore, different firms like SHS, Milupa and Nestle
produce a special powder, which can be bought in pharmacies or over the internet.
Because Jan doesn’t really enjoy drinking this mixture, due to its musty taste and smell,
he is the only one with PKU in Germany, who takes in all of his amino acid demand,
through tablets. This means, that he has to take in 180 pills a day. During our
conversation, Jan had to take his lunch serving of amino acids, 60 pills. I became
witness of Jan swallowing 30 pills in one gulp. Family J. holds that, every person, who
learns about PKU, once in his lifetime needs to try the amino acid drink. So, Jan
prepared one portion of the powder-water mix for me. As I tasted the drink, I knew why
Jan bothered to swallow 65,700 pills a year.
3.5
Problems because of PKU
To my question, which problems the family had to deal with because of PKU, Mr. J.
told me that, in the heads of many educated people, the picture still remains, that people
with PKU are retarded and are not able to go to a normal school. As he told me, even
Jan’s teacher was convinced that he had a mental disorder, even though, he obviously
stood there normal as any healthy boy. Moments like these, result from a great lack of
knowledge and in Mr. J’s mind there still has to be done a lot of educational advertising.
Other complications arise, for example when the family wants to go out to eat. As Mrs.
J. told me, “You could always be sure about the surprised and questioning looks on the
18
19
Attachment, p. 18
Attachment, p. 19
12
faces of other guests, when we put our weighing machine in the middle of our dining
table.” Naturally, because the family has a lot of experience with PKU, they can go out
to eat in every restaurant without a weighing machine. By now, even in some
restaurants, like for example Mc Donald’s, the phe levels of each food is written on the
menu.
On class trips some arrangements had to be made beforehand, but Jan also is so used to
the whole process, so that he is normally able to stay away from home for a few days
without any complications or risks for his health. Once in four weeks, Jan’s blood levels
have to be tested by a doctor. That’s why he has and always will require medical care.
3.6
School - job - future
Jan doesn’t have any worries in school, but he says, that it is a challenge for example, in
class tests, when, often as a result of stress, the phe level rises and he has problems to
concentrate. By now, especially before a class test he takes care of his phe levels very
thoroughly and keeps a very strict diet in order to prevent these concentration problems.
The phe level in the blood can always be affected by different, abnormal burdens, like
for example stress, sickness or physical exercise. Also at home, Jan’s parents sometimes
notice, when his phe blood levels are too high, when he is annoying, impatient or pushy.
However, this is normally an exception to his behaviour.
As far as jobs are concerned, there are only two jobs a PKU affected person can not
major in: racing driver and pilot. Apart from that, Jan already knew which job he wants
to be working in, in the future and that he wants to go to university to achieve this goal.
For his future every door stands open for him and this especially is a result from the
persistent caring and encouragement by his parents. At the same time, they were also
active outside their family. Thus, since 1992 Mr. J. is in charge of a support group for
PKU in his region in Germany. Mrs. J. regularly hosts baking and cooking weekends for
members of the group. 2007 her first recipe book was published. This book is a result of
her over many years collected recipes for the nutrition of her son. Due to their son’s
disease, the family’s life has changed for a great amount. To make the lives easier for
other families with PKU, they try to help where they can.
13
4
Conclusion
The key question phrased in the introduction, if one can life a normal life with PKU,
can be summarized like this: PKU is a hereditary metabolic diseases, which can be
diagnosed through a quick test, called newborn screening. If in this test PKU is
diagnosed, the right treatment is begun at once. From this point on, the child needs a to
his age appropriate PKU diet and a permanent medical attendance through a doctor and
a dietetic counselling. If this diet is maintained, the symptoms of the disease don’t set in
and the organism is able to develop normally. Indeed, I had the proof, that this is true,
when I got to know family J. Due to the parent’s commitment, Jan is able to live his life
independently and nearly without any complications and was able to develop a good
self-confidence. During my research, it has become clear, that when a PKU child enters
a family, it is indispensable, that from the first day on its parents treat the disease the
right way. To handle the daily life as easy as possible, there are organizations and selfhelp groups in Germany, who affected people should definitely contact.
After I dealt with this topic thoroughly, there are still questions open to be answered. On
the one hand, it would be interesting to know, if there are ways to diagnose metabolic
diseases, especially PKU, in poorer countries and if there are already organizations,
which care for these people locally. On the other hand, there is still disagreement with
scientists today, of who, how long and how strict, the diet should be maintained. I am
curious when the time will come, that enough experiences are made, for this question to
be answered.
14
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Heilbronn: SHS Gesellschaft für klinische Ernährung mbH, 2002
Awiscus, D. u.a.: Mit PKU gut leben!. Ein Buch für Jugendliche mit Phenylketonurie.
4. Aufl. Heilbronn, 1998
Grüter, Werner: Angeborene Stoffwechselstörungen und Schwachsinn am Beispiel der
Phenylketonurie. Stuttgart: Ferdinand Enke, 1963
Lyman, Frank L.: Phenylketonurie. 301 – 327 East Lawrence Avenue, Springfield,
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http://www.comidamed.de (03.03.2009). comidaMed – Institut für Ernährung GmbH
http://www.comidamed.de/metabolics.htm
http://www.dig-pku.de (02.03.2009). Deutsche Interessengemeinschaft
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pku 2009 vom 02.03.2009
http://www.metax.org/Events/snowfunpku/tabid/142/language/de-DE/Default.aspx
http://www.pkunews.org (02.03.2009). National PKU News
http://www.pkunews.org/news/news.htm
15