Episode 61: Phenylketonuria - Purple or Green?!? - Anatomy Of Illness

Episode Transcript
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(00:00):
Your gorgeous little boy Sam is just four months old. An age full of wonder and discovery. When he

(00:05):
was born he seemed nothing short of perfect. A beautiful bundle of joy whose laughter painted
your world with happiness. However, lately he has begun to exhibit some odd symptoms
that are concerning. A strange musty smell has begun to cling to him. An unsettling reminder
that something might be awry. And despite having all of his needs met, he often lets out a painful

(00:27):
cry that you just can't seem to fix. Additionally, he doesn't seem to be very present when you try
to play with him, which has raised some alarms. Because of these symptoms, you decide it's best
to bring it up with his pediatrician. Hello and Welcome to Anatomy Of Illness.

(00:56):
Today's episode is about phenylketonuria. Before we get into the condition, we are going to start
with the history. So why do we know phenylketonuria exists? Throughout the episode, I may refer to
this condition as PKU. We begin in 1934 with Dr. Ivar Asbjørn Følling in Norway. He was a
pediatrician at the time. He was examining a pair of siblings that had mental disabilities. The

(01:18):
mother of these two children had been persistent in trying to find the cause of these children's
disability, which eventually led her to Dr. Følling. He examined these children thoroughly,
even testing the children's urine for ketone bodies to reassure the mother. He did this by
using ferric chloride. Now, normally the urine would turn purple using this. However, this would

(01:39):
not be in the history section if the urine turned purple. Instead, it turned green, which is weird.
Before becoming a doctor, Følling was a chemist. So interestingly enough, Dr. Følling was able to
identify the cause of the green colour. Phenylpyruvic acid. This had never actually been
found in nature before. He concluded that it had been derived from phenylalanine from the diet.

(02:00):
He called this condition oligophrenia phenylpyruvica. Not long after the condition
would be observed by Jervis in the USA and in Britain by Penrose and Quastel,
who would give the condition a new name, phenylketonuria. Penrose suggested that the
mental disability and abnormal urine chemistry were caused by the same gene, but were too
independent effects. So they were not actually related. However, Vulliamy and Woolf would disagree

(02:26):
with Penrose. They instead would suggest in a paper that would be published in 1951,
that the mental disability would be a result of the high levels of phenylalanine. Essentially,
due to the high levels, it was causing an intoxication of phenylalanine. If you could
find a way to reduce the phenylalanine, you could find a way to relieve the symptoms. One
of their suggestions, which was dietary restriction of phenylalanine proved to be effective. Dr. Wolf

(02:50):
would propose an interesting idea, an artificial diet. This consisting of proteins with phenylalanine
removed, vitamins, minerals, carbohydrates, and fats. He had before worked at a drug company that
made protein hydrolysates for IVs. So theoretically it could be done. He suggested this to the
hospital. However, they were not as excited about the idea, telling him the condition was incurable

(03:14):
and he should focus on diagnostic tests rather than crazy treatments for incurable diseases. But
would this be the end? Thankfully, no. In 1952, Dr. Woolf was visited by a colleague
by the name of Dr. Bickel, who asked if there was any possible treatment for a patient he had that
had deteriorated so badly. So Dr. Woolf suggested it, telling Dr. Bickel he needed just enough

(03:37):
phenylalanine for normal growth, minerals, essential fatty acids, vitamins, essentially
making her a perfect balanced diet that would not cause a buildup of phenylalanine, considering her
body would not be able to break it down. Dr. Bickel initially thought the idea could never work,
but decided to try it because he had no other options for his patient. And with this,
she started to get better. There was a dramatic improvement in her behaviour. After seeing the

(04:00):
successes in the patient, the hospital, Great Ormond Street, would start to trial this and see
improvements in their own patients. This would also lead to the testing of the first infant,
as most children in the hospital would be between the ages of one to 12 years old when they first
presented with their symptoms. One of the children had a newborn sibling in 1958 who they tested the

(04:20):
urine of at 17 days old and found she also had PKU. Because of this, they were able to start her
on treatment from a very young age and she never developed symptoms. With this, it led to the 1961
large-scale screening program in Britain, which initially used the children's urine to test for
PKU. This would later be replaced by Guthrie's blood spot test, which was even more reliable.

(04:43):
If you have been enjoying this episode, don't forget to share it with a friend as it helps us
grow. What causes phenylketonuria? PKU is caused by a genetic mutation. This is in the phenylaniline
hydroxylase gene. Normally, this gene creates an enzyme that processes an essential protein
known as phenylalanine. But in the case of those with PKU, they have a lack of the enzyme or

(05:04):
reduced function in the enzyme that causes a buildup in phenylalanine. But how is this
condition inherited? So phenylketonuria is an autosomal recessive condition. This means that
both parents need to carry a copy of the faulty gene for the child to display symptoms of the
condition. The parents will not display symptoms as they are carriers of the condition. What can
cause phenylalanine to build up in PKU? When a person with phenylketonuria eats protein-rich

(05:29):
foods like nuts, meats, cheeses, or milk, or grains like pastas and bread, or even aspartame,
which is an artificial sweetener, this can lead to a dangerous buildup of phenylaniline in the body.
Speaking of body, if you want some comfy clothes to put your body in, don't forget to check out
merchantatomy.com for the coolest clothing options. So how do we test for phenylketonuria? Well,

(05:49):
in many countries phenylketonuria is actually screened for in the first few days after birth.
This is through a heel prick test, which is the same test we mentioned back in episode 2
talking about cystic fibrosis. This test is done after the baby is at least 24 hours old
and the baby has had some sort of protein. In this test, a nurse or a lab technician will
prick the baby's heel and collect a few drops of blood. This gets taken to a lab to test for a

(06:13):
variety of metabolic disorders, including you guessed it, phenylketonuria. With PKU,
this test will lead to future testing to confirm a diagnosis. These include things like blood and
urine testing. There may also be genetic screening done. This is to check for specific gene changes
causing the symptoms. We will get right into symptoms and presentation right after this little

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break. If you have been enjoying this episode, don't forget to check us out on buy me a coffee.
What symptoms might your child have if they had phenylketonuria? Now newborns don't initially have

(06:55):
any symptoms. However, with time and without appropriate treatment, children begin to develop
symptoms. These symptoms may include a mossy odor in the breath, urine, hair, and skin. This is
caused by a buildup of phenylalanine, neurological issues like seizures, skin rashes like eczema,
an unusually small head, this is known as microcephaly, intellectual disabilities,
behavioral, social, and emotional problems, lighter skin, hair, and eye colour in comparison

(07:19):
to their family members. This is due to the phenylalanine not being able to transform into
melanin, which is a dark pigment in the skin, delayed development, and mental health disorders.
What should a doctor be aware of when it comes to phenylketonuria? Some things a doctor should
be aware of when it comes to this condition are the types of PKU. These include classic PKU. This
kind is the most severe form of phenylketonuria. This is where the enzyme needed to break down,

(07:44):
phenylalanine is either missing or severely reduced. This then leads to high levels of
phenylalanine in the body, leading to severe brain damage. Less severe forms of PKU. This is the mild
or more moderate forms of phenylketonuria. So with this, the enzyme involved still has some function,
so the levels of phenylaniline are not as high. This leads to a lower risk of severe brain damage.

(08:07):
What are some complications a doctor should be aware of when it comes to this condition?
The complications a doctor should be aware of include irreversible brain damage and significant
intellectual disabilities. These occur within the first few months of life if left untreated.
Neurological problems such as seizures or tremors, major health or developmental issues,
behavioural, social and emotional problems. These are found in older children and in adults. Again,

(08:30):
all these problems occur if the condition is left untreated and undiagnosed. This is why
early detection through things like the heel brick test are very important.
So how do we treat phenylketonuria? Well, it is more about managing the condition as it is a
lifelong condition without a cure currently. So how do we currently manage it? Through early
intervention, you can prevent any intellectual disability and any major health problems that

(08:54):
PKU can cause. With this, it is mainly avoiding foods that are high in phenylalanine as the body
is unable to break it down, taking a PKU formula. This is a specially formulated nutritional
supplement that is used through the entirety of someone's life to provide enough essential
nutrition and proteins without high levels of phenylalanine. It has just enough of everything

(09:14):
that is essential for a person's growth and general health. There are some medications
that may also be used when it comes to phenylketonuria. However, these will not
work for everyone. These medications include sapropterin. This medication can be used in
combination with a PKU diet or for some people taking this medication can allow them to follow
a normal diet. However, this medication will not work for everyone. Pegvaliase-pqpz. This is an

(09:40):
enzyme therapy. It is used for adults who have PKU, but their current therapy does not adequately
reduce their levels of phenylaniline. This one is very uncommon due to side effects. So
usage has to be monitored. Are there any famous people with phenylketonuria? Yes, there is the
Irish actor, Mark Lavery. You may know him from the Foundation or Handsome Devil. He has PKU and

(10:03):
has previously talked about his experiences with the condition in interviews, being unable to eat
85% of foods due to phenylalanine. He has also discussed how lucky he is due to the more recent
discovery of the association between the diet and the condition and the early testing. So he
and his brother are able to live relatively symptom-free with their special diet. Is there
anything you can watch that features phenylketonuria? Yes, there is a short

(10:27):
documentary on YouTube called For Katy. This video highlights the importance of newborn
screening. As Katy did not receive this, it took 13 months for her to get a diagnosis.
Because of this, she had a buildup of phenylalanine, which caused some brain damage.
This documentary was made by Kevin Alexander, who was a filmmaker with PKU. He is an advocate for
newborn screening to allow for early detection, which provides the opportunity to prevent symptoms

(10:51):
from ever occurring due to early access to treatment. He also has a blog, podcast,
and Instagram where he discusses a lot about PKU, newborn screening advocacy, and rare disease
awareness. I will link his blog in the resources along with his Instagram and the For Katy video,
as I recommend checking these out to learn more about why it is important to provide newborn
screening. If you want to check out a foundation for those in the US, there is the National PKU

(11:15):
Alliance. Their mission is to improve the lives of people living with PKU. They help to expand
research into PKU and hopefully one day find a cure. They also provide education and support
to those living with the condition and their caregivers. For those in the UK, there is the
National Society for PKU. They provide reliable dietary guidance, support research and host events
throughout the year to allow for those who have PKU to have a community. They also disseminate

(11:39):
information about the condition. For those in Australia, there is the Metabolic Dietary
Disorders Association. They provide support to those who have been diagnosed with an inherited
metabolic disorder like PKU and their families. They help to provide connection with others
with similar conditions or the same condition and they provide education about these conditions.
If you want to check out the sources, social media links or any other links, you can head to

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anatomyofillness.com. If you enjoyed this episode and would like to hear more, subscribe to be
notified about our latest episodes. If you would like to join our community, we would love to see
you over on Discord or Instagram. Otherwise, stick around for the next episode.

(12:21):
Did you know there are hundreds of proteins in nature? However, your body only uses around 20,
with phenylalanine actually being considered one of the essential proteins.

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Episode 61: Phenylketonuria - Purple or Green?!?

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