Health Topics

Questions from Listeners

Andrew Schorr:

Welcome back to our live webcast as we discuss what are the problems when PKU is not treated effectively. Now Michelle has called into the studio. She's been holding patiently. Michelle, you have a child with PKU and have a story to tell I think?

Caller:

Yes, I was listening to your program today and I thought about my story and that it might be an appropriate time to share it.

Andrew Schorr:

Sure.

Caller:

I had my one and only daughter who was born in Monterrey, Mexico, three-and-a-half years ago, and we just had her, and they did the screening tests, but they only checked for thyroid and smaller issues like that. We had never heard of PKU, and it turned out that she did have PKU. She went undiagnosed until she was 13-months old. She did go through a lot of stuff, and I wanted to tell a little bit of her story if you guys will allow me to.

Andrew Schorr:

Sure, if you can do it briefly.

Caller:

Yes, of course. So my daughter was born normally. At about three months, she started regressing. She stopped using her hands. She stopped making eye contact, and then when she was about seven months old she started developing a seizure condition called West syndrome. As that started happening, she started regressing more and more until all she ever did was sleep and eat and have seizures. She was having about six seizures a day each lasting about fifteen-minutes long. Finally, we did do a lot of testing, and one of the last tests that we did was for PKU. She came out positive with a level of 18.

Andrew Schorr:

Whoa.

Caller:

That was with her eating already solid foods. We were feeding her chicken and things like that. They checked to see if she had a cofactor deficiency because apparently a level of 18 was not big enough to cause such a condition.She did not have a cofactor. We put her on the diet and about three to four months later her seizures stopped and she started coming back to us. She started making eye contact. She started smiling. At one year and a half, she started crawling. She walked a year ago, and now she's starting to say her first words ever since the diet was begun.

Andrew Schorr:

Yay. Thank you for sharing that story Michelle, and all the best. What's your little girl's name?

Caller:

Her name is Katherine.

Andrew Schorr:

Katherine, okay, that's great. I wanted to ask Dr. Arnold, so you hear this story and sort of a recovery like that, and maybe there are other things going on, but are you surprised or can just getting on the diet have that much effect?

Dr. Arnold:

Getting on the diet really can improve many people who are late treated. I think originally when PKU was discovered and they went back and started treating patients who were older, at first they were disappointed so people didn't really stress getting back on diet. Now we're finding particularly in young children that it can be very beneficial to go back on diet or just to begin the diet even if they've already suffered some brain damage or mental retardation.

Andrew Schorr:

All right. Question for Dr. Brumm. So related to getting back IQ, can we get back IQ or are we going to recover other things like mood, or some executive function. What can you get back when you sort of get with the program, if you will?

Dr. Brumm:

Right, well Andrew in Katherine's case she's such a young child, and there's ongoing brain development that's occurring, and this is hugely important, and different as Dr. Arnold pointed out in adults where you have a brain that's already formed. With little Katherine's catching up with her developmental milestones.It will be very important to watch her ongoing motor and mental cognitive development as she gets into her school-age years because she may have some learning difficulties as a result of her PKU. It would be important to monitor her closely with periodic evaluation of those skills so that we can actually track and see how she's coming along to really monitor her IQ and also the more specific cognitive functions. It's very difficult to say until she gets a little bit older because IQ in a very young child is not necessarily predictive of adult IQ.

Andrew Schorr:

All right, I do have one other question for you. So you're a neuropsychologist and one of the things you do is neuropsychological testing. At what point should kids with PKU have neuropsych testing, and what might come out of that? Should they be tested again at some point down the road or even as an adult for that matter?

Dr. Brumm:

Andrew, I think that's a very important question, and let me just refer back to little Katherine. I would strongly recommend that she be evaluated because she may, if she hasn't already. It would be very important to ascertain whether she needs early intervention for her motor or her cognitive skills to help her catch up as much as possible and help her reach her potential. For children with PKU, in general I think if they demonstrate any kind of a delay in reaching their developmental milestones, they should be evaluated. If there are any attention deficits or learning difficulties as they move into their school-age years, they should be evaluated, and depending on the level of severity of any issues that they may have, if there are problems with attention or learning or emotional difficulties, then they should be reevaluated every couple of years to ensure that they're getting whatever special support that they need, whether that's through special education in school or therapy if they're having any emotional issues.

Andrew Schorr:

Okay, and adults too?

Dr. Brumm:

Yes, and I was just going to add it's important that parents of children really communicate that information to their medical treatment team as well so that everyone has a really good sense of how the child is progressing.

Andrew Schorr:

And Dr. Arnold, you're in agreement with all that right?

Dr. Arnold:

Oh absolutely, absolutely. We probably at this point are not able to do a complete neuropsychology full battery on every child with PKU but particularly children who are having some performance issues. It can be very helpful. Sometimes the neuropsychologist can make recommendations for teachers or to parents that can kind of help them understand better the world as the child is experiencing it in ways that can help them.

Andrew Schorr:

We all know that there's sort of the grandfather in the medical management of PKU, and that's Dr. Richard Koch to whom I'm so grateful, and not only has he been on our programs but listens. He joins us now from Los Angeles, and I know Dr. Brumm you know Dr. Koch well because you worked with him at Children's in Los Angeles. Hi Dr. Koch. Did you want to make a comment?

Dr. Koch:

Yes I do because I've known Mary, the first patient you had on, since birth, and she has been very well controlled because of her family history, which you heard, and I think it's extremely important to point out that she had two severe mutations on the PKU gene, and theoretically should not be responding to BH4. I have found it to be true in several of my patients who had two severe mutations who originally were not in any of the studies for BioMarin because we didn't want to not show that there was no response. The important point is that it may be the emotional response you get to BH4 they in turn being much more important to success in life than some of the few points in IQ that we've been hearing about. I think Virdette would probably appreciate this point of view because the emotional makeup of a person a lot depends on how they do that and use it for success in life. I think especially in a marriage it's very important.

Andrew Schorr:

Right, we've talked about that. I want to thank you for calling in Dr. Koch and helping with any point of view you have on this, and I really appreciate it. So this is a great bit of information.

Dr. Arnold, I want to ask you a question. So often at a metabolic clinic, the thinking is well we need to manage the number, the Phe number, and the diet, and all these sort of clinical things. Is more of the discussion happening now on these subtle differences, mood, cognition? We've had parents on where they talked because Dr. Brumm was talking about processing in kids and just kind of how verbal they were and things like that. Is that something that's very much part of your conversations with family touched by PKU now?

Dr. Arnold:

Well, yes. It's part of a full understanding really of the lives of the children. We're quite interested in how they're performing in school and at home as part of the family and particularly attention deficits. We have suspected for some time that children with PKU have had more difficulties with attention. There probably are some biochemical reasons for that. Phenylalanine crosses into the brain using the same mechanism that the precursors for dopamine and serotonin, which are the neurotransmitters responsible for a number of things including attention and wellbeing. Phenylalanine can block the precursors of those chemicals from getting into the brain. Patients can have slight deficiencies of dopamine and serotonin that can affect the kind of executive functions that Dr. Brumm was telling us about, and also it can affect their sense of wellbeing. In fact most of the drugs that treat depression work by raising your serotonin. We suspect that people with PKU have a physiologic reason when their Phe levels are high to have a little bit less serotonin.

So, it's interesting now because it's getting more difficult to get PKU research funded because the answer is, 'Well, if they're not retarded any more, why do you want to get this grant and study their lives more?' And the answer is there's so much more to this than IQ. We want successful patients. We want patients that go on and become dieticians and who are successful in life, and so there's so much more to it than just IQ.

Andrew Schorr:

I have a question for you that came in from Jennifer in Shelby Township. I'm not sure what state that's in, but it sounds like a cool place, Shelby Township. She says, 'My daughter is 14-months old,' Dr. Arnold, 'and her Phe levels at 12 months were 3.2 on a completely unrestricted diet. My question is, how concerned do I need to be with limiting her protein intake, and what are the signs that she's getting too much Phe?' So with a little child, Dr. Arnold do you want to take that one?

Dr. Arnold:

That is probably a better question for the clinic where she was initially evaluate because I don't know what her Phe level was at that beginning. There's a little more information that I'd need to answer some of those questions. I would say that I would work with the clinic nutritionist as her dietary protein increases. Fourteen-month-old children are usually picky eaters. They're not eating double Big Macs, so the question is, is she able to maintain her phenylalanine levels on what she's eating now? The question is will that continue as she gets older and she starts to eat more protein. So at 3.2 certainly we would not restrict her diet, but I would stay in touch with her PKU program as her diet changes.

Andrew Schorr:

Okay. By the way we got a question from the Parazzo family and their three PKU children there. The oldest son, Anthony, had a question, and I think I know the answer. He wanted to know the total number of people in the world who are known to have PKU? The statistic I saw was 50,000. Does anybody know a different number? I think that's right. Hopefully, our research is right, but Anthony I think that's the number anyway, 50,000. You are not alone.

Here's a question for Dr. Brumm. Jean from Australia is listening. Jean wrote in 'I'm a 41-year-old adult with PKU. I live on my own and find cooking for myself difficult. We have very limited low-pro food options in Australia. I was taken off diet when I was 11-years old, and my general practitioner tells me that I just need to get back on a low-protein diet, but I can't and I'm tempted to give up. Do you have any advice for someone in my situation?' Dr. Brumm, any suggestions? We may ask Mary too, but do you have any suggestions?

Dr. Brumm:

Yes, and I'm sure Mary will be able to help answer Jean's question and give her some suggestions too. You know we have many patients who are in a similar situation. I think one of the things that is going to be so important is that Jean with her general practitioner get hooked up with a clinic that can help her really monitor and get back on diet and help her with all of that in a supportive way. I think it's crucial that she have support through a medical metabolic clinic, In addition, support from family and friends has been known to help individuals with PKU deal with this very important but difficult to achieve diet. Having a positive attitude about it and just really feeling that they feel the support and that it's something that's attainable has also been shown to be an important factor and making it manageable. Hopefully Jean will find a way in which she can work with her GP or like I said a specialist to help her come up with a regimen that's going to be manageable for her. I would defer to Mary to address those more specific issues.

Andrew Schorr:

Right, well let's ask Mary. Mary, you've been doing it all along pretty well, not perfect as you said, but you're going to have adults come in who are in situations like Jean and whether they're in an area like Australia where she feels they don't have a lot of options if that's true. What would you say, because it seems really daunting to try to go from not really managing well to managing it perfectly? You don't have to see it as climbing Mount Everest do you?

Mary:

No, and I know it is very difficult especially for adults who have been off diet for a long time. One of the major functions that protein has in our diet is it helps us to feel full after a meal to provide satiety. So if all of a sudden we take that away and they're on a really low-protein diet, that's one of their real struggles that I hear is that they're hungry a lot but yet they can eat a lot more food if they're going to stay on a low-protein diet. That's where some of those low-protein foods can be helpful.

I think another thing that's very helpful and would be important for her to be hooked up with a specialist or a metabolic clinic or resources that way is if she is taking a formula. Formula fulfills that function of the protein and it helps provide that satiety or helps her to feel full, so that would be a real important part of her diet. And there're lots of different formulas. Formulas used to be really nasty and they're still not that great, but there are so many more options than there used to be. If she could get hooked up with a metabolic clinic where she could try some samples or find a formula that works well for her. That was one of the biggest issues for my sister when she went back on diet after being off for years; she just can't stand the formula, she couldn't tolerate it, but there are so many more options now that she has been able to do really well.

The other thing is if there are not a lot of low-protein foods available, fruits and vegetables are wonderful things because they are naturally low in protein. They have a lot of fiber in them which also helps with people feeling full and satisfied like they were able to eat something. So, if there aren't a lot of low-protein foods available, I would just really encourage her to incorporate a lot of different fruits and vegetables into her diet.

Andrew Schorr:

Okay, very good point. Here's a question that came in via e-mail from Susan, and I think we'll have this go to Dr. Arnold. Dr. Arnold, this is what Susan writes, 'It has been conveyed to me from my son's genetic team that several weeks or more of Phe levels being too low would be cause for alarm. Are there physical and/or brain growth issues from this scenario? When do you sound the alarm?'

Dr. Arnold:

In a person without PKU low phenylalanine levels are what we expect because our body is processing it. In someone with PKU, we don't like the levels to get too low because phenylalanine is what we call an essential amino acid. It means your body can't make it. So if the level is too low, it means there might not be enough around for growth, body growth, brain growth. So on a chronic level, we wouldn't want to leave it too low for a long period of time. On a short-term level, particularly in children who don't always grow with a steady rate, they sometimes grow in spurts, and so sometimes if they're having a growth phase and using it all up, their level will drop down a little bit. So short term, we tend to not worry about it. A few weeks probably are fine. If it's stretching into a few months, you start to worry about it a lot more.

So this is again something that it helps to be able to talk about with your nutritionist. You get one level that's low you check it again, if it's still low you go up on the Phe, and then of course eventually the growth spurt or whatever was making it low will end, and then you'll have to readjust again.

Andrew Schorr:

Okay. Dr. Brumm, here's a question we got in from Jim. It's kind of long, but I think it's an important point. So Jim writes, 'I'm 45-years old. I have a BS and an MS in industrial environmental microbiology, and I've worked in the pharmaceutical industry for 20 years at midlevel management positions. I have classical PKU, and I've been completely off my diet since I was about 14 years old. At this time the only thing I consciously avoid is anything with aspartame in it or another artificial sweetener. I was treated and monitored until I was about 16 or 17 at Boston Children's by Dr. Harvey Levy. I've never had any of the significant cognitive or emotional problems or side effects that I often hear about when not being on the diet or not diligent about it.' So here's the question, from Jim, 'What are the long term effects of chronic elevated Phe as I age, and will there be issues that will manifest later in life?' Dr. Brumm, any thought about that?

Dr. Brumm:

Andrew, I think Jim's question illustrates the tremendous potential there is for people to succeed and do very well in life with PKU, and also the variability as Dr. Koch has always pointed out in his research. Jim has been off diet and has clearly been able to function very well and achieve many goals in life. So the question of what the long-term effects of chronic elevated Phe are as one ages is a research area that we're really looking closely at. We don't have data on the long-term outcome in adults. It's something that we're really still investigating. The issues that Jim might be faced with, as we all are to an extent with normal aging, would be the cognitive issues that we've talked about earlier tonight, which have to do with executive function, the higher level cognitive skills, processes speed and attention. Those are things which he may notice as he ages; he may notice that he's not thinking as efficiently or that his mental flexibility or speed of processing is not as good as it was in the past.

The fact that he hasn't had any noticeable problems up until now bodes well, but as we've talked about in the past hour a lot of times folks may not be fully aware of these subtle cognitive deficits. So I think it's important that Jim monitor and be aware of his cognitive functioning as he gets older. If he does have any issues that start interfering with his occupational/professional performance or his emotional wellbeing, he should talk to his treatment team about that.

That's a very good question because this is an important area of emerging research in the future.

Andrew Schorr:

All right. To be continued. I just want to ask one question of Dr. Arnold about research. So some people who follow this closely saw that there was a phase I study results of 25 patients that came out about sort of an injectable, longer-acting medicine. Now phase I is way off…any comment or is it just wait and see what happens with that because it seemed like it was positive but again it's a very early trial. Is that right?

Dr. Arnold:

Right, it's an exciting outcome to the phase I trial. Phase I is where a drug is tested for us to begin to understand what kind of dose is needed, how the body handles it, how the body gets rid of it. Then we move on to phase II which is where you refine the dose, refine information, begin to refine information about side effects, and then on to phase III which is usually the large clinical trial, and if people have the opportunity to be in a phase III trial I hope that they will be. So it's exciting. It's very exciting that we may be able to take a shot that will give you the phenylalanine hydroxylase enzyme. There are a lot of questions that are unanswered. How many people will be allergic to it? How big will the shot be? How many people will be willing to take a shot versus not? So I think that we have a lot to learn, but it's really a very exciting beginning.

Andrew Schorr:

All right. Well we have so much ground that we've covered. I want to thank you Dr. Georgianne Arnold for joining us from the University of Rochester and the Children's Hospital there; Bridget Reineking who joined us from the Children's Hospital of Wisconsin in Milwaukee; Dr. Virdette Brumm who joins us from Monterey, California; and I want to just have a last word from Mary Brown who's in Cedar City, Utah. So Mary you've heard all this and you've been living with it, and you have two siblings earlier with PKU, are you encouraged, and for people listening feel that they can have a long and successful life?

Mary:

I think it is encouraging. I think the research is moving in the direction that it needs to. I agree wholeheartedly with a lot of the comments that have been made. It's not just about IQ. My IQ has never been a problem as far as performance in school or ability to take and pass tests or do any of those kinds of things that we base a lot of IQ function on, but the places I started to notice, and it took awhile I think that there could be many adults that may not notice some of those more subtle effects. It took me a while to really think about it and think, hmm, could this be different? And it could. That was the exciting thing for me to find out is that it could be different, and I could maximize my potential to achieve even more in life. I think that that's probably the goal for every person or every parent who has a child with PKU is just to maximize the potential of that individual. I think the research is definitely trying to move in a direction that supports that.

Andrew Schorr:

Mary Brown, thank you so much for being with us and wishing you well and just congratulations on your success in life and really being an inspiration for so many people. Well we've covered a lot. I want to just thank some organizations that have helped you know about this program and their ongoing really partnership in what we're doing; the National PKU Alliance for spreading the word about the programs, and if you're not familiar with them their website is npkua.org; also the Georgia PKU Connect; and also the PKU Organization of Illinois.

Now, we're going to be doing another live webcast coming up right after the July 4th weekend on July 7th, and that is "How does PKU affect you and your relationships?" For a little kid birthday parties etc., we've talked about that a lot, adolescents for sure, and then what about adults? We're going to talk about that coming up on our next program. Always we welcome your comments and questions. Send them to PKU@patientpower.info. Thank you so much for joining us. Tell others about our programs and remember you can find them all at www.patientpower.info/pku. I'm Andrew Schorr. Remember, knowledge can be the best medicine of all. Good night.

Please remember the opinions expressed on Patient Power are not necessarily the views of BioMarin, our partners, or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That's how you'll get care that's most appropriate for you.