To mark Undiagnosed Children’s Day 2018, Sue Routledge, Rita Francisco, Amanda Riggs Rackerby and Eleonora Passeri have shared their own experiences of diagnosis and misdiagnosis. Their blog is split into three sections, each written by the different contributors. We would like to thank Eleonora for curating the stories and editing the final blog, and thank everyone involved for taking the time to write their experiences for us and the rare community.

Undiagnosed, misdiagnosed, underdiagnosed: So, what can we do? by Amanda Riggs Rackerby and Eleonora Passeri.

My journey on awareness started when I looked into the blue eyes of a young girl.  She looked like an angel with her curly blond hair.  This young angel had struggled against an “unknown devil.”  Her parents knew the name of her illness, their diagnostic odyssey was over.  They were one of the “lucky” ones.  As a scientist, when I was still working in the lab and dealing with biological samples of unidentified “subjects,” classified as having X or Y disorder, I never thought about being undiagnosed.  A few years passed and my career then took a different path and I forgot about these undiagnosed patients.  Then a mom reminded me of the existence of “In-Limbo-Patients.” Many people and their families perpetually continue their diagnostic odyssey.  I used to believe that getting a diagnosis would then lead to a cure.  I was young and very optimistic.  From talking with patients and their mothers here are some things I have since learned:

1. Undiagnosed: 1 in 20 patients are defined as undiagnosed and only 1 in 3 get a diagnosis after a genetic test.

2. Misdiagnosed: Misdiagnosed means that some patients get the wrong diagnosis. Time is precious when you are sick, so a misdiagnosis can have severe consequences for patients and families.

3. Underdiagnosed: Underdiagnosis happens when a person knows something is wrong, but it cannot be named.  Giving a name to a disease is crucial because you need to know what you are fighting against in order to win.

I would like to see science help these patients, so what can we do?  The first step is talking with them, they are the experts by experience, and they know the disease better than anyone else because they live with it 24/7.  Researchers, medical doctors, and healthcare professionals should take into consideration what the patients are saying rather than assuming nothing is wrong with a patient just because the problem cannot be seen.  Trust is integral in these cases.  I introduce to you below mothers and patients who are still searching for a diagnosis. Today I challenge scientists to take a radical step and use a bottom-up approach by embracing these patients and mothers of patients.  Start talking to them and listening with serious consideration.  If this approach leads to faster diagnosis and more effective therapies then how can this approach be ignored?

The misdiagnosed Pitt-Hopkins army by Sue Routledge.

40% of rare disease patients are misdiagnosed at least once.  For someone with a rare disease the mean average length of time from symptom onset to an accurate diagnosis is 4.8 years (from Shire report).

Parents need the correct diagnosis for their child.  Often there is no treatment but with an accurate diagnosis they can look for support groups and organizations that can help.  They can learn about what is common in others with the same condition and solutions others have found which might help their child too.  They may learn the possibilities of having another child with the same condition and can make an informed choice to have another child.  Pitt Hopkins UK, a registered charity, hopes to raise awareness of Pitt-Hopkins syndrome among medical professionals so more children will receive the correct diagnosis.

My son was diagnosed with Pitt-Hopkins syndrome when he was almost 16.  He was tested for a few syndromes but he was tested for one syndrome 4 times.  4 different doctors had tested him for Angelman syndrome, eventually concluding that he probably had a variation that could not be found by tests 20 years ago.  We didn’t accept the diagnosis as we were convinced it was not correct.

Pitt-Hopkins syndrome is an ultra-rare neurodevelopmental syndrome.  It is a differential diagnosis for both Rett and Angelman syndrome, which are both rare but not as rare!

A poll of the Pitt Hopkins UK group last year showed that out of 41 families replying, 33 had been tested for Angelman syndrome before receiving their Pitt-Hopkins syndrome diagnosis.  A recent poll of the UK and international group found that out of 60 that responded 39 were tested for AS with 6 receiving a clinical diagnosis and 32 had been tested for Rett syndrome with 6 receiving a clinical diagnosis!  Of course, these children are in families that now know their child was misdiagnosed.  We don’t know how many are out there are still misdiagnosed!

The winding road to a Congenital Disorders of Glycosylation (CDG) diagnosis by Rita Francisco.

(256 w) CDG are a family of rare metabolic diseases with over 130 different types.  As the name suggest, these conditions are caused by defects in the machinery that assembles, processes and attaches sugars to proteins and fats, converting them into glycoproteins and glycolipids, respectively.  Approximately 50% of all of our bodies’ proteins are glycoproteins, they are present and play various roles in all of our organs: This explains why most CDG types and patients have complex, multi-organ clinical presentations.  I have just been sharing the basics about CDG, but you can already see that this story has all the ingredients to make diagnosis difficult, confusing and full of setbacks – both for families and professionals!  But, what I haven’t told you yet is that, as it happens for many rare diseases, doctors don’t often think “Oh, we should test for CDG!”.  So, lack of awareness should be added to the top of the list of ingredients contributing to the underdiagnosis and misdiagnosis of these conditions.

There are 3 main tests – divided into 3 main stages – that can help diagnose CDG:

1. Screening: Transferrin isoelectric focusing – despite its long, complicated name it basically involves getting a blood sample and running a fairly simple assay;

2. Gathering proof: Protein/metabolite-based assay – to measure their activity/presence/amount;

3. Confirmation: Genetic tests.

This is my appeal to you: “Thinking it is metabolic? Think it could be CDG!” and run some tests. We might all be surprised by the number of medical mysteries we end up solving and the lives we give direction to.