I'll tell you what I want, what I really really want!

The other day I listened to my daughter as she picked up the phone, dialled her bank and started to explain what she wanted done for an automatic payment to go to into my account.  She was polite, completely engaged and knew exactly what she wanted.  I have to say that I was impressed. 

She explained that she had special needs and that her benefit covered so much but that she wanted to make sure an extra $5.00 went into her Mum's account so as she could pay back the money she borrowed. She knew exactly what to do and how to do it.

It started me thinking about all the things our kids know how to do and how so many manage, to get by in the world.  There is so much they can do and understand, but the potential for failure and the potential for being misunderstood, not to mention the potential for fallout from unthought-out consequences is high.  Which means that someone in their lives must be one step ahead the whole time. 

My daughter likes to go shopping, wants to have lay-bys, wants to buy presents for everyone,  The consequences don't matter to her because she lives in the here and now.  Warnings about  running into a lot of debt simply pass her by because there's always another payday, The idea of saving money is an anathema to her - what good is putting money aside to spend later when you can spend it today?  Her idea of saving money is to buy from op-shops (and who can argue with that)!

The concept of something unforeseen such as a vet fee for the cat, an unplanned visit to the doctor, a need to go to the dentist, or to make sure there is catfood in the cupboard at the end of the week, is as absurd to her as water-divining.  Much better to rush out and buy the boyfriend a Valentine's Day present in the hope of getting something in return!

She's quite happy that her bank balance comes in as zero each month as it's better to owe money in lay-buys, or 'next month' for the doctor, than to see money resting fretfully in her bank account.

It's difficult to argue with mainly because she will agree with everything I say... then go out and do exactly as she pleases.  And, I have to say that I am fully expecting the $5.00 per week to be uninstated any time now!

There's always another day...

Exciting new bloodspot screening

(The following is a summary from James O'Brien, IPWSO Board member, from Australia, who attended the recent IPWSO Conference in Toronto)

A Novel FMR1/SNRPN methlation test for Fragile X Syndrome and chromosome 15 imprinting disorder screening of symptomatic children and newborns.

By David Godler, Cyto-Molecular Diagnostics Research Laboratory, Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Australia.

David Godler spoke about his research into newborn bloodspot screening over the past 18 months, primarily into Fragile X diagnostic. Recent funding from the Foundation for Prader-Willi Research, USA, has enabled David to expand his work with fragile X to include the Chromosome 15 imprinting disorders: Prader-Willi Syndrome (PWS), Angelman Syndrome and 15Q Duplication Syndrome.

The presentation was about David’s two new methods of testing blood collected in a tube and blood spots from adults, children and newborns. A newborn blood spot is the tiny spot of dried blood on blotting paper that is already taken through a heel pin prick for almost all newborns within the first few days of life in many countries. The tests currently performed on this material identify 30 or so conditions including phenylketonuria, hypothyroidism and cystic fibrosis, but not PWS.

Initially David and his team developed a new Methylated Specific Quantitate Melt Analysis (MS-QMA) test for Fragile X. To enable him to test 100,000 newborn bloodspots he also developed technologies to automate the process and to confirm positive findings. He is now able to test 100 samples in 90 minutes rather than the old 2 to 3 day turnaround for each test. At the same time his team developed new software to monitor both the results and accuracy of the test, and this method had been published for Fragile X. Accuracy of this test appears to be nearing 100%.

The beauty of his new test is that it can be performed on blood spot material left over from other routine testing. This means that the babies suspected of PWS would not be required to undergo collection of another blood sample required for more traditional diagnostic methods. It would also mean that the PWS babies that may not be tested for PWS and initially missed because they may be premature or may not have typical PWS, would be picked up by this new test. This would be because newborn blood spot testing reaches virtually all babies born irrespective of symptoms, but current PWS testing is only performed on babies that show symptoms that are recognized by doctors to be associated with PWS.

David’s first step in PWS test development was to analyse blood DNA samples from patients that had PWS symptoms, with only 9 patients confirmed to have PWS by standard DNa testing. From the first 30 symptomatic referral samples tested, his MS-QMA test confirmed 100% agreement for samples positive by standard testing. In addition to these  3 previously undiagnosed cases of PWS were identified. In order to prove that his new test was not simply showing false positives, David needed to develop an even more accurate second line confirmation test.

His second test he has called CINQ Droplet Digital PCR, which looks at individual methylated and unmethylated chromosomes suspended in miniature droplets. Exact details of how this new test works (or what the letters even stand for) are not yet published, however, its accuracy appears to be much higher again than standard testing, able to detect abnormal methylation down to an unprecedented less than 0.1% in the PWS deletion group. Furthermore, the new test has confirmed positive MS-QMA results missed by standard testing, and is showing that a number of previously diagnosed Uni Paternal Disomy (UPD) individuals may actually be Triasomi 15. The unexpressed male 15 chromosome appears to be hiding in the background rather than showing up on previous more traditional tests.

Furthermore, a new group of Mosaic PWS is likely to emerge. David is doing some further work on this subset. (With mosacizm PWS may not be present in every cell in the body. Depending on which cells in the body have the PWS variations may result in changes in how the characteristics of the Syndrome present, especially in UPD).

So, what does this mean for children with PWS?

• ·       David and his team have come up with two new and seemingly very accurate methods of testing for PWS using blood spots and other sample types.

• ·       The tests appear to be picking up previously unconfirmed cases of PWS.

• ·       A new subset of T15 within the UPD group seems likely.

• ·       A new phenotype of Mosacizm is possible.

• ·       Bloodspots can be taken at newborn or at any age, resulting in a less invasive, more accessible and sensitive method of obtaining a PWS DNA test than is currently available.

 Where to from here?

 In 2015 David and his team have been awarded a large NHMRC grant to test 100,000 newborns for fragile X (the world’s largest fragile X prevalence study), and is hoping to use the remaining materials and expensive infrastructure initially developed for Fragile X, for PWS testing. Funding is currently an issue for this larger project, and David is now applying to multiple granting bodies to make this possible. In a less expensive project, over the next 3 years David and his team has started recruiting and assessing PWS patients to perform analysis of how the low level mosaicism identified by his two new tests related to variation in severity of PWS, especially in UPD. Concurrently, PWSA Australia has commissioned a Health Economics Report to analyse the financial benefit of early diagnosis. If the test is proven accurate, David and PWSA Australia will approach State or National Newborn Bloodspot Screening Programs with his two tests and our Health Economics Report to apply for the inclusion of PWS in their testing programs for all babies born in Australia.

If admission to the NBS programs is successful:

·       We should start to see a diagnosis within a few days of birth avoiding unnecessary multiple tests and prolonged family stress when waiting for a diagnosis.

·       Doctors, specialists and scientists will be able to develop a more detailed understanding of the various phenotypes of PWS, possibly enabling better targeted clinical interventions.

·       Testing of all babies will give a definitive answer regarding the prevalence of PWS live births in Australia.

David cited individual colleges that are assisting in the research from Cyto-Molecular Diagnostic Research Group, Victorian Clinical Genetics Services, Royal Children’s Hospital, Victorian and New South Wales Newborn and Metabolic Screening laboratories, Genetics and Learning Disabilities Services (Newcastle and The Children’s Hospital (Westmead, Sydney).

David also acknowledged assistance from a number of organisations including VCGS, Royal Children’s Hospital Foundation, The Marion and EH Flick Trust, Australian Government, Thrasher Research Fund, and Foundation for Prader Willi Research

Note: This report is James O’Brien’s understanding of David Golder’s presentation and may contain inaccuracies in its interpretation. 4 August 2016

I was a Conference Virgin

I was 38 years old and still a virgin - a conference virgin, that is.  My third child, diagnosed with PWS, was already 4 years old, but the shock of this diagnosis had not worn off, in fact she was not diagnosed until she was 3, so all our lives were still in a state of flux.  Life was definitely not fair.

In the 80's there was very little information on PWS available in our country then, and certainly no Association or support.  My information came via rather ancient printed copies of the USA "Gathered View" which the only other person I knew who had an older child with PWS had kept stored away in her garage.  Somehow I heard the news that there was to be a conference in Perth, Australia and the speaker was to be a Professor Vanja Holm (known then as the Godmother of PWS in the States).  I was determined to go to a corner of the world I'd never been to before, to listen to people speak on a topic I'd never heard of before, and... fly there.  I hated flying and had loathed it ever since my first flight on an elderly DC3 which shook and bounced its way under and through the clouds and fairly close to the mountain tops.  My mother said she'd come with me. 

Dr. Vanja Holm (front) the first physician to be involved with Prader-Willi syndrome in the United States. Front: Dr. Vanja Holm. In back left to right: Dr. Hans Zellweger, Dr. Gene Deterling and his wife Fausta (founded of the Prader-Willi Syndrome Association-USA), Dr. Andrea Prader and Dr. Sam Beltram, the first Prader-Willi Syndrome Association (USA) president. Taken at the national conference in 1984. Source: Prader-Willi Syndrome Association (USA)

Nervously I boarded the plane.  Confidently, my mother did the same.  She appeared to enjoy the inflight entertainment and certainly enjoyed her meal.  I couldn't eat.  I couldn't concentrate.  I felt every air-pocket for 9 hours.  I was nervous about the conference, I was nervous at leaving the children at home and I was surely nervous about the flight.  We landed, collected our bags and found our way to the hotel.  It overlooked a pedestrian square which was full of people going about their business, shopping, going to work, enjoying the Perth life-style.  Not so confident was their overlooker.

My mother didn't come with me to the conference, so I was completely on my own.  It was like diving off the high dive board into water so deep I couldn't touch the bottom.  I could barely make it to the surface before I sank again into a very watery world full of questions and answers that seemed to float by, but I could never seize.  I went from room to room; I listened to lecture after lecture - delivered by confident specialists who seemed to know what they were talking about.  It seemed so concrete as they imparted fact after genetic fact, rule after rule, warning after warning.  I thought of my small daughter back home, with her smiling face and lovely warm hugs.  I felt her tiny arms around me, saw her own determination to survive in this unforgiving world, and it was only by remembering her boundless love for life that I managed to get through those three days.

After the conference, my mother took me on a bus tour to see the wild flowers of Western Australia.  It wasn't quite the right time of year for it, but I do remember seeing a field of the most vivid purple and exclaimed in delight at what, to me, was beauty and perfection.  The bus-driver overheard my comments and turned on his microphone so that the whole bus could hear..." Yeah, well, that field over there?  That's full of 'Patterson's Curse'.  It's a weed."  He paused for effect, so I felt suitably cowed.  "However," he went on, "it's also known as 'Salvation Jane' as it can be a food crop in the drought."

Under my breath, I said to my Mum, "well, it's probably the prettiest thing I've seen yet".  She firmly agreed.  And I've thought about it often.  How weeds survive.  They're strong.  They don't give up. They are always there, no matter how much you try to weed them out!

Anyway, since that first nervous conference, I've been to many, many more.  I went to the first IPWSO conference in The Netherlands, I've been to places I would never, ever have been to - Taiwan, Romania, South Africa.  I've learned to separate the factual lectures from the child or adult with PWS, because everyone is different.  I've learned to enjoy the company of other parents, and how easy it is to talk freely with them.  I've learned that the knowledge passed on by specialists is something we parents are privileged to share at this level, and I've made good friends with many of our professionals.

First-time conferences are never easy.  I've learned to recognise the lost look on parents' faces, and to sit and talk and share my own experiences.  I've learned to laugh out loud at the things our kids do to try to win the day and have been bent over in hysterics on many an occasion.  I've raised a glass and sung many a good song.  I've also wept and cursed the unfairness of life, but I've learned such a lot about life as well.

If our 9th international PWS conference is going to be your first; be encouraged by what you are going to learn, be uplifted by the friends you are going to make, and, above all, learn to be strong.  To be a 'salvation Jane'.

Dietary Management in PWS - the absurdity of it all!

By MH

I recently had the great pleasure of interviewing a group of parents about dietary management in PWS.  The interviews were recorded for a training film and were designed to find out the practical actions that parents take to manage food. 

The commonalities in both problems faced and management strategies applied were striking.  One speaker after another spoke of stress being caused by peas rolling off plates and the need to have replacement peas close at hand!  Surprisingly to me, grandmothers came in for particular and consistent criticism for giving inappropriate food to people with PWS. 

Many parents, I am delighted to say, were able to laugh at the absurdity of it all.

Of course, this all led to me reflect on what I (a parent of a son with PWS) do and, in particular, led me to think about some of the odd things that I could never have imagined when I first heard of PWS.

For example ...

My son refuses to use a knife.  I'm pretty sure it's because he knows that he is not allowed to put his knife in his mouth and is terrified at the prospect of some food sticking to his knife that he will then not be able to eat.  So, I either cut his food for him (which he doesn't like as he considers himself too old) or he laboriously attempts to cut it himself using the side of his fork.   

I increasingly find myself not finishing the food on my plate until my son has finished his own meal.  Why?  It's in case some mishap occurs to an item of food on his plate that I then need to have a immediate replacement for. Most of the time I'm not even conscious of doing this.

I "sneak" food.  When I find myself hiding in my utility room (which isn't visible from any other part of the house) eating a piece of fruit, I usually don't find anything odd about my behaviour.  But every now and again, I am reminded that this is all slightly RIDICULOUS.

I have concluded that I cannot give my son a full apple, not even a very small one.  Why?  Because he invariably eats the core and then becomes upset.  I know that he doesn't intend to eat the core, but worries so much that he may leave an uneaten piece of apple behind that inevitably he swallows everything and then starts to worry.

I regularly find myself having to call my son repeatedly when his meals are ready.    I assumed that my son's interest in food would rapidly propel him to the table for each and every meal, but no, this is not what happens.  Rather, if he is in the middle of another activity his desire to finish the activity is usually greater than his desire to come to the table.  As a result, at least every other day I find myself repeatedly calling him while the rest of the family sit waiting.  This was not what I expected PWS to look like.

I regularly lie about food.  In fact, lying is probably one of the strategies I employ most frequently in dealing with dietary management in PWS.  So, if my son asks (for the 3rd time!), if I checked the expiry date on his yoghurt, I will lie and claim that I did.  If he asks what I have been doing in the utility room, I will, without any guilt, invent a story that has nothing to do with food.

I felt privileged to have an opportunity to listen to other parents talking about how they manage food.  Hearing what they did made the absurdity of it all even more obvious to me.  It also made me feel proud to be part of a group of people who have found ways to cope with what is a supremely difficult task and, sometimes, even manage to laugh about it.

*** 

I always remember a mother of an adult son with PW being called out of the house by her neighbour just as the roast dinner was ready.  She hid the full roasting pan in her husband's wardrobe...  Editor