Monday 26 October 2015

ESPKU conference extras! An interview with the President of ESPKU!

Eric Lange is the President of the ESPKU society and while waiting in the airport for our plane back to London, I was able to ask a few questions! 

Do you or your children have PKU?

My daughter who is 30, has classic PKU.

What was the reason for joining ESPKU?

I joined the UK's NSPKU in 2009 and went to ESPKU conference. It was amazing to meet people from other counties with different perspectives, NSPKU is the oldest association 43 years.
Mainly my interest is in executive functioning, so this really excited me.

Have you ever tried the PKU diet/drinks/food for yourself?
If so, what did you think?

I haven't tried the diet but I've tried all the mixtures except the newer ones. 
I thought I'm glad I don't have to drink them regularly! 

How do you feel the conference went?

Excellent! I wouldn't expect anything less from the ESPKU.

What are you most excited for when you organise these events?

I'm excited for the new speakers and to see how the country reps have done in the last 6 months or a year. It's interesting to see the reps spark off each other in discussions. I thought the video of the undiagnosed is good for the scientists to see, to see that this is the reason we are all here. It's amazing to have the range of speakers and great to have the American PKU's. 

What were you nervous about?

I was nervous about the opening speech, you've got to show everyone you're human!

What do you hope the PKU's got out of the conference this weekend?

They can learn from other PKUs from other countries how they monitor their intake of Phe and that they can learn recipes - although that should be a given! That they can swap ideas what they can do in their own county meetings. I also hope they can create life long lasting friendships. 
I also hope they learn more about the history of PKU! 

What do you hope the parents of the PKUs get out of the conference?

Knowledge and empowerment!
Supporting them with advocating PKU in their local area.


Are you excited or wary about the new potential treatments for PKU?

I'm always excited and I'm always wary!

What words of encouragement would you give a parent with PKU or a person with PKU themselves?

"Don't worry, be happy!"




ESPKU Conference Conclusion

This has been an amazing weekend for me and it's been such a roller coaster ride. From the emotional meeting of the relatives of the people who's discoveries saved my life; to the complex and interesting studies of the potential future treatments of PKU. I have met people that have such passion and love for their families, their patients and for the improvement of their own lives. 
The theme of the conference was building bridges. Many permanent bridges have been built for me, I have made friends with so many wonderful passionate people and I have met many companies who design and produce the food I am eating every day and are always striving for new products. 

At the end of these conferences I like to think to myself, what have I learnt? What will I take from this experience and put it into my life back home?

What I've learnt is that there are people even now still fighting my corner for a better quality of life. I have learnt that even though the low protein food situation in the UK is not ideal, I am very lucky with what I do have and what I can eat. I've learnt that Germany is a beautiful country which I would happily go back to in a second! 

What can I take from this experience?
I can take home the feeling of knowing that I am not alone in this, that there are people who can support me and go through the exact same feelings I do. I've taken home a few more ideas for food and recipes and maybe, just maybe the thought that I can always do better with my diet. There is no more excuses for not eating properly, it just isn't worth it, I will try harder as I know and I've always known it's what's best for me. 










ESPKU Conference, Final day - Part 3

PKU in the next decade
Speaker: Prof. Harvey Levy

The therapy for PKU works to reduce the Phe level in your body.
We are now looking at the two ways of treating PKU, diet and co factor.

Diet
- is the standard response to the disorder of PKU
- it applies to all PKUs

Co factor (Kuvan, PEG-PAL etc)
- usually works on mild/moderate PKU's
- only rarely works with Classical PKU's



European study showed that when PKUs were treated with Kuvan
Very mild PKU's out of 178 tested, 77% were almost certain to respond
Mild PKU's out of 112 tested, 44% around half responded 
Classic PKU out of 267 tested, 6% responded meaning barely any responded.



So what was learnt was Classic PKU's rarely responded and even when they did respond, complete response is very rare. 
Most responders have mild PKU so do not even need treatment to begin with.

PKU treatment in 2025 we can predict: 
Diet will still be here
- Co factor
 - Kuvan will still be here
- Alternative enzyme therapy - peg pal
- Enzyme replacement therapy - maybe?! 
- Gene therapy - ?
- Gene editing - ?

In more detail: 
Diet
- will it be needed? Properly - some may still prefer diet compared to drugs!

Cofactor (Kuvan) 
- it will be there 
- Will be preferred with those completely or almost completely as this will be the only alternative that can be taken orally, others you'll have to inject. 

But the main point is in 2025 you'll have the choice!

Alternative enzymes therapy 
- will it be available? Yes!
- May be replaced by the real enzyme therapy 
- they may give a form of the enzyme replacement

Peg pal 
Metabolises Phe in a different way, it creates NH3 and trans-cinnamic acid
It does look very promising and will hopefully be approved within the next couple of years


"Real enxyme therapy"
Like current treatment for the lysosomal disorder - gaucherie disease 
It will reduce the phenylalanine hydroxylase 
The problem is phenylalanine an unstable enzyme outside of the body.
They have not yet been successful in stabiling it outside the body, so it can not be put into a test tube so it can be replicated and injected into the body. 
In the next few years it could be stabilised to then it could be replicated and fabricated.
So what will happen is the future is that we'll be able to replace the mutated enzyme with a working enzyme.

Gene therapy
It's been talked about for 20 years, but there is still no ability to replace the mutant gene 
- There will still be no safe gene therapy 
- It has to produced as a virus so w have to know it is safe before we do it 
- it is Improbable this will be there in the next 10 years

PAH gene editing
This is an exciting prospect!
This can be used for editing the gene mutation in the body by putting it back to the normal state. 
This process is called CRISPR. 
The process of this that is a nucleus that cuts into the gene. The NRA guides the cutting protein to the proper portion of your DNA where the mutation is located in the DNA it then allows the nucleus to cut into that point it separates the double DNA then it injects the normal base into your DNA. You change the abnormal mutation in the gene into a normal gene. 
If you imagine it is like editing a book, you are replacing one letter in a whole book to make the book work.
Will it be available in 10 years time?! Maybe!

2025

- Diet will still be present
       - for who? The first 2-4 years diet will still be on diet.
       - adolescent and adult years will be trying out alternative therapies

- Enzyme gene therapy 
       - Will not be used in the first years of life.
       - After ages of 2-3-5 therapy can be used.

Gene editing if it is safe and effective then it can be used by everyone of all ages!

"50 years I have been involved I've never seen a more exciting time for the treatment for PKU."

What really excites me about all these talks about the future of PKU, isn't just the potential of new treatments, the personalisation of the diet and the growing of social media to reach new people and different counties. It's the fact that these scientists, dietician and other professionals are still working hard every day to make a better life for PKU's. They aren't giving up, they aren't just happy with an 'okay' diet. They want the best for us and they are always looking for new ways to make our lives that little bit easier. Most importantly they have given me hope, hope for the future and hope that maybe one day I will be able to live my life everyday without worrying about my next meal. 




ESPKU conference, Final day - Part 2

Prof. Rani Singh: 
What will change in nutritional management in PKU?

What does the future hold?

Nutritional therapy and adjective therapies (kuvan, Peg-PAL etc)

"Let they food be thy medicine, thy medicine be thy food" -Hippocrates 

It is important to remember that no matter how many drugs come in the future, diet will still be the most important thing.

Some roles of groups and sciences in development of nutritional management of PKUs:
- Medical science/laboratory science
- Food science/laboratory science
- Nutritional science/dietetics

The lessons that have been learned over the years:
Initiating screening early 
Life long diet is necessary

Deficients 
There is a lack of adequate supplement with vitamins and minerals in medical foods for infants, this is an issue that still needs to be dealt with.

The PKU diet is proven an effective treatment, but what health risks persist?
- weight gain/obesity 
- bone mass reduction
- nutritional problems
- neurocognitive deficits 
- growth retardation
- Neuropathy 



The prediction for the future is that we are going to see a more personalised diet for each individual PKU.

As a PKU and a consumer of the products our challenge is:
- do we know our diet?
- do we know what our food and amino acid drinks contain? Are we lacking in vitamins?
- we should be challenging our dietician to look at our diets and telling us what is missing

It's important that diet is personalised so we do the get nutrients that may be missing from our diet if we do not eat the correct things.
We need to focus on the gut as well as the brain.
In the future when choosing a medical food and personalised therapy it becomes very exciting and critical to PKU's wellbeing

The dream is one day is that we will have global guidelines! 
Social media empowers us to question our diet and lives compare to others around the world. 
The main point is even though lots of drugs come out, don't forget how important the diet is. 


ESPKU conference, Final day - Part 1

After sleeping in (oops!) and scoffing down even more sausages for breakfast, we went to the final meetings of the conference. The main theme being the future of PKU, where will it be in 10 years time?

Phenylketonuria - Pathogenesis driven treatment strategies
Speaker: Pro. Dr. Francjan van Sponsen

The future of PKU
in the future they are looking at more Pathogensis driven PKU treatment. It was agreed from the research that the diet is amazing, and it should not be forgotten that PKU is the first metabolic disorder that is able to be treated with a diet to help stop mental retardation. No other metabolic disorder had been treatable before PKU. 
However, are we just satisfied with the diet?! The answer is no!


The issues with the diet are:
- There are still problems with IQ and EF 
- The behaviour and social aspects
- the quality of life is still poor for some PKUs
- Bone density is still a problem
- with the elderly we still do not what will happen in the future!
- with young adults there is still a lot of issues and the diet is very socially demanding.

Other treatment options.

All the alternative treatment being studied now are focusing on the blood concentration of the Phe in the blood, but not towards the brain. With PKU we question why is the brain the only organ affected, the only symptoms and signs of PKU are in the brain. 
However, what is really confusing is that there are some untreated PKU's out there who do not suffer any brain damage, even though they've been on a high Phe diet all their lives. We are still not sure why this is. 

Blood Brain Barrier (BBB)
We know the amino acids travel up the spinal fluid and when it gets to the blood brain barrier, it stops too many amino acids getting through to the brain. However the problem is because there is already too much Phe in the brain, the Phe gets through the BBB but no other amino acids can, creating the side effects some PKU's feel (concentration problems etc.) because the white brain matter is disturbed. 



Trying to find the correct treatment

There are three ways of treatment
Myelination
- Neuromatter synthsesis
- Brain protection by nutritional compounds 

Myelination
We know these things:
Lowering blood Phe - lowering brain Phe
Lowering blood Phe - increasing other Large Neutral Amino Acid (LNAA) 

Brain neurotransmitter 
This is the same as myelomation, we know: 
Lowering blood Phe - lowering brain Phe
Lowering blood Phe - increasing other LNAA
By giving BH4?
Giving more BH4 gives the brain more protection by lowering the blood Phe, it then lowers the brain Phe. 

Brain protection by nutritional compounds 
This is protecting the brain Phe levels by having a low Phe diet.

BH4 works on the Phe but not on all patients, it only works on around 30 - 40%.
And unfortunately peg pal is not being studied in Europe yet.

At the moment all research is based on:
Knowledge of yesterday 
Facts of today
Dreams of tomorrow 



What I've really found fascinating with my PKU experience is the older I get the more I am learning about what PKU is, not just a diet and a drink to have every day but a genetic disorder that affects my body in different ways at a cellular level. It's so wonderful to come to these conferences and learn even more about the science behind PKU.




Friday 23 October 2015

ESPKU conference, Day 2 - Part 4

There was quite a few talks from PKUs who had travelled all around the world and it was fascinating to hear their stories of what they struggled with and what they found easy. It's really great to hear stories like this, because it encourages me that just because I have a restrictive diet, it doesn't mean it limits me in what I can do with my life and where I can go, the world is a lot more accepting and understanding place and I am lucky that w have so many good products around the world that are easy to travel with and buy when I get to those countries. 

Today is now finished but it's been so insightful into the struggles the first diagnoses and how far PKU has come in all those years. Going around the stalls its exciting to see all the new products out there and that people are making from across the world, from biscuits to puddings to pasta! 
Of course it is just so nice to be around people that are of similar mind, that have faced the same struggles as you and have had the same experiences. PKU can be a very lonely diet if you aren't in contact with anyone, so you always feel like you are different and 'weird' compared to everyone else. To sit and talk with people who have the drinks, who eat the food really makes you feel, even if for only a small time, like you are normal. 



ESPKU Conference, Day 2 - Part 3

So I've been to a lot of small meetings, so I'll try and do a small summary of each one!

Geir Ivar Elgjo Følling: How my grandfather discovered PKU

So the grandson of the person who discovered PKU talked a little bit about his life, the man of course is Ivar Asbjorn Følling. For this reason PKU is also known as Følling's disease. 
He had done many studies earlier in his life in chemistry but later he discovered PKU as a mother came up to him with her two children, both had healthy births but as they grow they steadily declined mentally and physically. They also had a strange oder on their bodies, that was giving their father bad asthma attacks, which is the reason why they came to Følling. Følling studied them and found they were very restless, they had very fair skin and very bad eczema. When he studied and tested their urine, it was found when he put iron chloride in the sample, the urine would turn bright green in colour, which turned out to be an excess in phenlypyruvic acid, which is what blocks the enzyme that breaks down Phenylalanine. 
The grandson talked about how he remembered his grandfathers one time working with 20 litres of urine to study and test!
In 1962 he received the John P Kennedy Jr award for his work in discovering PKU.
The grandson said a very touching quote Følling said.

"I don't like the phrase Knowledge is not power, I would say Knowledge is humbleness."  






ESPKU Conference, Day 2 - Part 2

Newborn Screening
Patricia S. Guthrie: My father's journey to screening

We then had a talk from the daughter of the man who invited the newborn screening of PKU's - Robert Gruthrie. 
She talked about her fathers passion for getting the screening out to doctors and hospitals, as a father of a PKU child, the only tests that were done was at the age of 2, which by then was far too late to stop any of the affects of brain damage on PKU's. When he discovered that PKU can be detected through a test of the blood of a newborn, he was passionate about making sure every new born was tested. In America in this was very difficult to do as the doctors did not want to be told what to do, even though the parents weekend fully supportive of the screening, as they had already had children with the damaging affects of untreated PKU and they knew if they had another one, the same thing could happen again.
Robert travelled the world making sure every government saw that this new born screening was vital to every child born. 
When he died in 1995 a scholarship was made in his name, supporting young people who wanted to learn.
This was an incredibly touching talk as Patricia said when her father was researching and travelling the world, she never really knew the affect he was actually having as it was all normal to her and nothing out of the ordinary. 
She said coming here, she saw a young child running around having fun with his parents and she realised her father was the reason that child was healthy. 
At this point I was in tears as this made me realise the personal impact this man had on my life, this woman's father was the reason that I am now a functioning happy adult, he is reason I am not heavily brain damaged and I can cope and understand my diet from a young age.   


ESPKU Conference, Day 2 - Part 1

I woke up this morning still not believing that I was in Berlin! I went to breakfast and to my shock I was sitting there having a full English! The sausage is from Germany and tastes like sausage! It was amazing. 


Presentation of the European Guidelines
Speaker: Prof. Francjan J. Spronsen 

We then had our first talk about European guidelines for PKUs, it was very interesting.
They were explaining they had been writing up and researching guidelines for the last 2-3 years. The stronger the evidence they got, the higher the evidence mark they achieved and it would make the research more valid. The lowest mark is a D and the highest is A. The guidelines overall achieved a B mark. For such a rare disease that is a really good mark, we could never achieve an A because there just isn't a big enough sample sizes and PKU is so complex. 

They then discussed the key recommendations from the guide.

Key recommendations 

Initiation treatment 
- If children tested have a level higher than 360 then they need to be treated.

Life long treatment

- RECOMMEND TO ANY PATIENT WITH PKU, this is such a great thing as the question of whether PKU is 'diet for life' has always been ridiculous for me, as I always feel the full affects when I'm not following my diet properly.
- Research found when diet is discontinued thee are poor outcomes such as concentration problems.
- The report showed the was neurological complications when PKUs weren't diagnosed.
- Improvement in mood in adults when they go back on diet (quality of life)
- There no evidence that it is safe to stop diet.

Life long follow up 
- All adults should have life long support in specialised metabolic centre

Target Phe levels
- Up to the age of 12 the levels should be between 129 - 369
- 12 and older including adults 120 - 600
- There is very unclear evidence of what happens with Phe levels in adult and adolescents compared to what happens with children. 

Target Phe levels in pregnancies 
- should be 120-360
- if levels are kept low evidence shows that there are no affects on children, so there is no heart problems or IQ.

Nutritional follow up
- there should be an annual nutritional review for those on a restrictive low portion food

Bone density 
- Measure once when PKU's are 12, when BMD is abnormal the measurement should be repeated next year
- Evidence found that early treated PKU's had low bone density but still healthy range

Neurocogantive follow up

- The question was at the beginning should we be measuring it? The researched showed that it definitely should be tested.
- Evidence showed neurocogantive problems is the main outcome of PKU
- We should be measuing it at ages 12 and 18
- It should also be measured if parents, teachers or doctors are concerned about development.

Transition 
- All patients should be supported in a specialised metabolic centre. 

As I said earlier, the confirmation of this reports are very comforting to me especially, that it is diet for life, that there is no evidence to support it is safe to go off diet, so it gives me less excuses when I do cheat.  


Thursday 22 October 2015

ESPKU Conference, Day 1 - Part 2

So we arrived at the conference hotel earlier than the expected time, as people who worked with Nutrica all around the world wanted an introduction session to welcome us.
I then met a wide range of PKU's, it was very overwhelming! I was shaking hands with people from, Croatia, Spain, Portugal, Ireland, France and of course Germany! I had never been with such a wide range of people in all my life! But everyone was friendly, I think everyone was excited to see more PKU's across the world.
The cooking section for the welcoming party was how to make low protein Sushi.
Needless to say I was sceptical! How can you have sushi without fish?! Is that even possible? 
The chef showing us was from Germany and he explained you can use the low protein rice, the seaweed wrapping you can still use as its low in protein and instead of fish you just use different selections of vegetables, cucumber, pepper, radish, carrot etc.
The chef made it look effortless, using the rice, vegetables, seaweed sheets and using the bamboo mats to roll it all together. He finished with a beautiful product of sushi.
However... When it was our turn it was a different story! It really is amazing how someone can make something look so easy but it's only when you try it yourself, you can see the real skill needed to end with an amazing product.
Either way, everyone agreed the sushi tasted delicious and I'm shocked to say I will definitely be trying this at home! It's simple, healthy, delicious and actually a lot of fun!

 



I've met lots of new people and have already made friends with a few of the people from Ireland, which is really lovely, as I do have family roots there. I look forward to tomorrow, when the conference starts properly and the talks begin!

ESPKU Conference, Berlin, Germany. Day 1 - Part 1

I was contacted in July by Nutrica about the possibility of coming to the ESPKU conference in Berlin, all expenses paid!
I had previously written an article for their website piece on "How do you PKU?" I wrote my article about fitting a PKU diet around a working life in the office.
Of course, as soon as I had read the email I knew I wanted to go! For me, this is a great chance to go to another county, learn a new culture and go to a conference for specifically for and about PKUs, an international conference at that!
There is an annual conference for people in the UK, but living down in the South East of England, they are usually too far away for me to travel, so I do feel I have really been out of the loop of what's been going on in the PKU world.
So here I am, sitting on a plane to Berlin! I feel very excited.
I'm really looking forward to learning if there is any new updates in technology or the study of PKU in people (I dare not say the word "cure"!)
I am definitely looking forward to the food! Most hotels I find have really loved the challenge of having to cater to a new diet and having to use different products and methods. The food I've had previously has been shocking how delicious and "normal" it looks. When I've gone with my mother she usually prefers the PKU options over the normal high protein selection!
Ironically, the only complementary snacks available on this flight were a Danish pastry or a ham and cheese roll! Even though I'm hungry, I realise I'm probably surrounded by people who are all going to the same conference so all know what PKU is! I had better behave myself!
One thing is for certain, I have a very exciting weekend to look forward to!

PKU (Phenylketonuria)

Hello everyone, in this blog I'm going to talk to you about my PKU life, but as its so rare I know a lot of people won't have heard of it, so please see below for a quick introduction to PKU. If you want to know more information, please comment your questions :)


Introduction 

Phenylketonuria (PKU) is a rare genetic condition that's present from birth (congenital).

The body is unable to break down a substance called phenylalanine (see below), which builds up in the blood and brain. High levels of phenylalanine can damage the brain.

PKU is treated with a special low-protein diet, which reduces the levels of phenylalanine in the body and prevents brain damage.

PKU doesn't usually cause any symptoms if treatment is started early. If PKU isn't treated, damage to the brain and nervous system can lead to:

  • learning disabilities 
  • behavioural difficulties 
  • epilepsy  

High levels of phenylalanine can also cause eczema.  

Read more about the symptoms of phenylketonuria.

Phenylalanine

Phenylalanine is an amino acid (a "building block" of protein). The phenylalanine in your body comes from protein in your diet, particularly high-protein foods, such as:

  • meat 
  • fish 
  • eggs 
  • cheese 
  • milk 

What happens?

The body takes in phenylalanine from the digestion of protein in the gut. Once it's entered the body, phenylalanine is either used to make proteins or removed by an enzyme (protein) called phenylalanine hydroxylase.

In people with PKU, phenylalanine hydroxylase doesn't work properly due to a genetic mutation (alteration in their DNA). As a result, phenylalanine levels in the blood and other tissues rise. 

Read more about the causes of phenylketonuria.


(Information taken from NHS Choices website http://www.nhs.uk/Conditions/Phenylketonuria/Pages/Introduction.aspx)