Series 3 episode 1. Mary Humphries: The doctor didn’t listen! A delayed diagnosis of MODY

Mary Humphries tells how her son Dan was diagnosed with diabetes aged 16 and it was assumed he had type 1 diabetes and treated with insulin.  On insulin he had terrible problems with low blood sugars frequently losing consciousness and not managing to concentrate at school or at home.  Mary was very worried that he was getting worse on the insulin and asked about genetic tests because she had recently been diagnosed with Type 2 diabetes and there was diabetes in all generations of her family.  She was not listened to; the insulin was continued, and Dan got worse.  Searching the internet for answers she found the Exeter diabetesgenes.org website which led her to talking to Andrew and Maggie. 

They were able to rapidly diagnose that this was Maturity-onset Diabetes of the Young (MODY), subtype HNF1A . with a genetic test.   Maggie  helped Dan to stop his insulin and get excellent control on a quarter of the sulphonylurea tablet called gliclazide.  Dan rapidly improved off the insulin and passed his A levels with flying colours going to Bristol where he achieved his life’s ambition to become a large animal vet.  

Transcript

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Welcome back to the One in Six Billion podcast. Today we're going to talk about familial diabetes of the subtype which is also known as maturity onset diabetes of the young or MODY. And this is genetic diabetes that runs in families being passed from one generation down to the next. And we're really delighted today that we've got Mary with us to explain her experience of being diagnosed with this type of diabetes.

So we're so pleased you could join us, Mary. Could you introduce yourself to our listeners? Hi, I'm Mary. I'm a wife, a mum, a granny, a retired nurse, and along with my son, Dan, we have Moody Diabetes. So thanks so much for joining us, Mary. I wonder if we could go back to the beginning when you and Dan were first diagnosed with diabetes. Could you tell us about that?

Yes, it's quite a long time ago now, but I was always aware of diabetes as most of my family had it. And it was always a case of when would I get it rather than if I would get it. And I'd had gestational diabetes in each pregnancy, but it was never followed up. And then I started getting very tired and I think just had a routine.

know, blood screening at the GPs and they found that my blood glucose was higher than it should be, but not outrageous. And I was diagnosed with type 2 diabetes and just started looking after myself, which is basically what I've been trying to do anyway. And then a few months later, our son, Dan, who was 16 at the time, he was very fit and active and well. And one day,

He'd been doing a summer job working in a field for a farmer and he phoned me at home and said, can you bring me a load of water? I'm really thirsty. So we took him three litres of water. And in the evening, when he came home from work and I was doing the family meal, I put a big jug of juice on the table for the whole family and he picked it up and drank the lot. So I said to him, I'm going to test your urine after tea.

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because I had urine sticks, which is what I'd been given. And his sugar levels just shot off the end of the stick, as it were. And that's when it all started, really. So it was out of hours, so I'm only out of hours GP. And they told me to take him to hospital, which we did. And they'd obviously been told a new...

Type 1 diabetic was coming in and they were quite surprised when this fit and healthy looking 16 year old just walked in. They did his blood test which showed his blood glucose was higher than it should be but sent him home again because he was so well and said just bring him back the next day. So we took him back the next day and they just said straight away well he's type 1 diabetic we'll get him on his insulin and then you can go home again.

And that was how it started. And what was your reaction to that?

Heartbreak that our son looked like he had this disease and knowing what it could mean and he'd just done his GCSE, smashed that, he was working towards wanting to be a vet and it just felt like everything was crumbling. But I was also surprised that he wasn't unwell.

And I was also surprised, they literally started him on insulin, showed him how to use the pen and after a few hours didn't even stay overnight, back home. And that was it. And at that point, were you or any of the doctors looking after him questioning the diagnosis of type 1 diabetes? Because I'm aware, as you say, you had a lot of diabetes in the family being passed down from grandparent to parent to...

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a child, so I'm interested in what stage you started to question whether this really was type 1 diabetes or something different. At that stage, because that all happened in less than 24 hours, it was mainly poor Dan, this is dreadful, and sort of trying to keep him going because he had his emotions to deal with. He'd just started sixth form college and really setting off on life and it looked like it was all crashing down.

A few days later, a diabetes nurse came to our house and I'd started to think about this and we'd already got a family tree with all the diabetics marked as it were and I asked her about genetic testing and she said, Dan is 16 now so I listen to him, I don't listen to you. And I thought that was horrible.

Days later we had an appointment with the consultant and said I was diagnosed as type 2 a few months before, Dan's been diagnosed as type 1, my father was diagnosed as type 1 and he said well that can't happen and showed him the family tree and at that stage nine out of eleven of us were diabetics, either type 1 or type 2.

seemingly depending on where we lived and who diagnosed us. And he just wasn't interested. That must have been really hard. You're in a very difficult, stressful situation anyway with your son being told he has a lifelong disease that will require him to take insulin for the rest of his life. Yes. And the kind of feeling that you weren't able to question anything or ask any questions that they weren't being listened to. Every question we asked

was shot down. At that stage, because it was still early days, Dan in himself was still very fit and active. But in a matter of weeks, the longer he was on insulin, he became ill and iller and iller to the point that he had to stop college. And we couldn't really leave him alone and he'd be passing out every evening. So when you say he was ill, the problem was that he was

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losing consciousness. Yes and he just wasn't himself, he just felt awful, he just wasn't done anymore and he was frightened and we were getting frightened. Our next visit to the consultant, he asked for a blood test which would show something that would see if he was type 1. Do you know the test I mean?

Yeah, so you're talking about the pancreatic antibodies which are usually positive in type 1 diabetes aren't they? Dan had that test and it came back that it didn't show that he had type 1 diabetes. So we thought at last but the consultant said he has, it's just slow developing and he wrote a letter to RGP and the

diabetes nurse actually stating this patient does not have moody diabetes. So that's fascinating that he'd actually considered it and said it wasn't there, although there was no supporting evidence saying it was type 1 diabetes. And I think Dan was ill because he was taking insulin and this was resulting in his blood sugar going low. And so the loss of consciousness and the change in how he felt.

was because his blood sugar was below normal values. So he wasn't needing the insulin. It was actually making him unwell. Yes. And yet there was still no room for listening or questioning. No, no. It came to a head very, very soon after that. David and I had to go out for about three quarters of an hour one evening. So we had to leave him and his brother was at home.

And we actually had fish and chips for dinner, which we don't normally have, and gave him a massive portion thinking he has to be okay on this lot. And gave George his brother Lucas aid and stuff and said, Ring, we're only going to be gone three quarters of an hour. And after 20 minutes, we had a phone call saying, can you come back? He's passing out again. And at that stage, I can remember saying to David, my husband,

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this isn't right, it isn't supposed to go like this. Because I had nursed new diabetics, know, type ones, and they were poorly, and they got better when you gave them the insulin. And all along, I thought the insulin wasn't right. I really wanted to take him off it, but I knew that was not the thing I could do. And I just thought, I've got to sort this out myself.

no one else is going to listen. So the next day I went online and put Dan's symptoms in and after a couple of hours an Exeter page came up and I read it and I thought that's Dan, that's him. And I rang our GP who was actually excellent and he went online at the same time and we're reading it together and he said yes that sounds like Dan. But then he said

but I have to be loyal to the consultant, my hands are tied, I can't do anything. By this stage we thought Dan was going to die. We really believed he was going to die.

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Wow, it just sounds so frightening and you were doing everything that you could as a mother to try and find the answer for Dan. Yeah. So what were your next steps? I think I asked my mother to phone and she spoke to Andrew because I was just having an intelligent conversation was beginning to beat me because my whole reason depth was to try and save Dan's life.

and Andrew then spoke to me and I told him about it and I think Andrew might have actually had some contact with some distant members of my family. I don't know if that's true or not. I think that is true. I think I'd known about another branch of the family. Yes, cousins who we weren't really in touch with and Andrew, you told me I'm

sure this is Modi and you told me what to do and sort of looked after us then. So how did you feel Mary having that conversation with Andrew? Massive relief, absolutely massive relief. I thought it would be okay we can sort this out.

you think your song's going to die and then suddenly someone's listening.

It's untold relief. And the actual test would have required a blood sample to be sent to us. How did you go about getting that? Was your GP happy to help with that? I think from what I remember, Andrew, you've actually phoned the consultant and had a chat with him and sort of said, this is Modi. And the consultant then phoned me and it was extremely nice.

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and said, you need a blood test, when would you like to come in and have it? We all sort of read carpet treatments and we'd done and I both had our blood tests on the same day. And then when we got the result, the consultant phoned up and said, would I like to go in and talk about it? And I said, no, no. I just remembered something which might be pertinent. Between ringing Exeter the first time, talking to Exeter,

and getting test results, the diabetes nurse rang and I told her I'd spoken to you and she was furious and really told me off and she said that just makes things very difficult for me what you think you're doing. But by that stage I didn't care I had to save my son's life and I know that sounds melodoratic but that's how it was.

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So you had managed to use the phone number which was on the website as a way of getting in touch. And were we then able to support you through the next bit? think Maggie was involved, wasn't she, with the decision? Because now we've got a firm diagnosis. We knew insulin was not required. But it's actually how you did those steps. Yes. Once I'd been in touch with Exeter and...

you told me what to do. I think I then met Maggie for the first time and blinging down off insulin and I was given phone numbers day and night for the next few days to be in contact with someone at any time if I was worried.

Dan sort of picked up within 24 hours, he was back to his normal self, well almost back to his normal self after coming off the insulin. So we stopped Dan's insulin and we'd started him on just a tiny dose of a self -annulure tablet called glycozide? That's it, a tiny tiny dose, yes.

And I remember Dan telling us how he tested his blood sugar 48 times over the first 24 hours because he'd been told he needed insulin to survive because of the original diagnosis of type 1 diabetes. So he couldn't quite believe that stopping insulin was going to be OK. And he wanted to check his blood sugar really frequently to make sure he'd be fine. Yes, he couldn't believe it. He went for a really long bike ride as well.

which he hadn't been able to do anything at all. So it's just like the world opened up again for him. He had a future, we had a future. I mean, obviously my test was positive too, but I managed on diet for quite a long while. But we were just giving our son back and he was giving his life back.

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And I remember when Dan had been on insulin and having these low blood sugars, the hypoglycemic events, he'd had to stop his driving lessons as well, hadn't he? He'd had to stop everything. He stopped college, he stopped driving lessons, he stopped sport, he stopped going out. He had to stop everything. So give us an idea of how Dan's life transformed once he started on the tablets. Well, he was basically Dan again.

which was brilliant. He had always wanted to be a vet since he was little. He'd worked with cows and he wanted to be a dairy vet. And he got to university, got to Bristol and succeeded in becoming a vet. He's now got his own dairy business. He's about to become a daddy, which is going to be the biggest shock ever to him. And life is good.

That's fantastic to hear and in fact I remember you phoned me up the day Dan got his A levels because you felt that he was going to fail college when he'd been given the diagnosis of type 1 diabetes and put on insulin. Do you remember that conversation? I know he thought because he'd missed so much he would fail and yes him getting the straight A's he needed it was tell everybody because you played such a big part in that.

I remember that conversation. fact, I remember telling that story at many conferences afterwards when I spoke about Dan and told his story so other people could be aware. And it always made me feel quite emotional, that story of, you know, he'd got through his A levels and got the grades he wanted to do, do what he wanted as part of getting that right diagnosis. I think I actually sent you a photo of him with his favourite cow. You did.

And I think this whole story really shows sometimes professionals are very bad at situations where they are outside their knowledge area. And rather than saying, I don't know, I will find out or that's interesting or that's unusual to become defensive, which is what you were dealt with. And, you know, thank goodness that you were able to use the internet because I remember when we put up that

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website. We said it was for patients, their families and professionals because we knew that things are changing, that we don't just get our medical information from professionals, we now get them from the internet and we thought that was really important because it was such an unusual diagnosis that that was available. I think there's a couple of things I'd like to say about that and I don't know if it's partly my

You should always listen to your patient's instinct, especially parental instinct. It shouldn't be ignored. I think you know your child particularly. I if you've even got the evidence like our family tree for that to be ignored. But I'd also like to say to medics, and I'm bunching you all together and I'm sorry about that, but if you have a patient,

and you start them on treatment and they become iller and iller and iller to the point that parents think they're going to die. Please be prepared to just think out the box for a minute. I think that's such an important message, Mary, and in fact very similar to the message we heard on our first podcast with mum Emma talking about her son Jack where she was convinced he had neonatal diabetes and had to go and talk to her consultant and try and...

persuade him that she knew it was different. you're absolutely right to flag that a parent really knows their child. And if a mother's concerned about their child, then really to listen to that parent is super important. I think that's the big thing we just weren't listening to.

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So Maggie, I think that was a wonderful description of the problems that people have of being diagnosed when they have a rare genetic form of diabetes. Yeah, absolutely. And I remember Mary telling me how she'd actually drawn out their family tree showing the diabetes going back four or five generations with the diabetes being passed down from grandparent to parent to child and still being told, well,

We're not going to do genetic testing. We'll never take him off insulin. What's the point? So what a struggle she had in terms of getting that right diagnosis. Yeah. And I suppose if we just think about the mathematics of it, if you're 16 and you have diabetes, then it's around a 98 % chance that it is type 1 diabetes.

So if you just say every case is type 1 diabetes, you'll be right 98 % of the time. The problem is when you're not in the 98 % and you're in the group who have majority -unset diabetes of the young or MoD. Yeah, and I guess if we think of some of the key characteristics that we find in patients with MoD, you'll typically see this what we call an autosomal dominant pattern of inheritance with the diabetes being passed from a parent in one generation to the next.

And typically many of them are diagnosed below the age of 25. So because of that age of diagnosis are often, as you say, assumed to have type 1 diabetes. And the other thing is that they will often be slim, unlike people with type 2 diabetes who when you're under the age of 30 would typically be very overweight. again, that makes people think it might be type 1 diabetes. The crucial difference as

Mary and Dan have shown is that they are not dependent on insulin, that they go on making insulin. And so what are the key tests that the doctors should be doing when there's a question? So Mary talked about the pancreatic antibodies, which we suggest, and in fact, NICE guidelines also suggest are done close to diagnosis. So testing GAD, IA2 and zinc transporter.

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which are typically positive in those with type 1 diabetes, which shows an autoimmune cause. But in MoD, we would expect those antibodies to be negative. So the other thing, when people are on insulin, you can't really tell whether they need it or not unless you do a test called C -peptide, which measures how much insulin an individual is making of themselves. And this test is most useful.

some years after diagnosis of diabetes, so probably three to five years after diagnosis, when people with type 1 diabetes are out of what we call the honeymoon period. And typically, those with type 1 diabetes won't have measurable C -peptide or have an extremely low level, showing that they're no longer making insulin of their own. Whereas our patients with MODY will continue having measurable C -peptide, showing that they're continuing to make insulin of their own and therefore don't need.

injected insulin. And so in fact the situation now with the national testing for genetic diabetes is that if you're diagnosed with type 1 diabetes and all three antibodies are negative and you're making insulin as shown by C -peptide then at that point you qualify for NHS testing.

And the other thing that people might find helpful is our, what we call our MoDI calculator, which is available on our diabetes genes website, where people can put in just eight basic criteria and click on calculate probability. And it gives them a score as to how likely this patient is to have MoDI or monogenic diabetes. Yeah. And that avoids needing to turn everybody into an expert. They can actually put in simple clinical data and that will say,

how likely it is to be moley and that can be extremely helpful. And a couple of things that Mary talked about in terms of Dan that are really key features of the gene that affects their family, the HNF1 alpha gene. We know that these patients tend to show sugar in their urine at a lower, what we call renal threshold. So they'll show sugar in the urine before there's even a problem with blood glucose.

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And when Mary did the test at home, she found really high levels of sugar in Dan's urine. And also the fact that he managed on just a quarter of a glycozide tablet. And we'll hear in subsequent episodes why patients with HNF1 alpha are particularly sensitive to really low doses of sulfonylureas. So again, those were elements that are particularly found in HNF1 alpha diabetes. Yeah. And this HNF1 alpha diabetes is

with the second commonest cause of MoDi after glucokinase. And interestingly, in previous episodes, it was the one that Tim Frayling and Sian Ellard were involved in setting up in Exeter very soon after the gene was discovered by Graham Bell in Chicago. I suppose just a final thing to say is if you've got any questions about could I have MoDi, the best place to go,

is our diabetes genes website, is diabetesgenes .org. And there you will find lots of information aimed at both patients and professionals dealing with all aspects of diagnosis and treatment.

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So it was just wonderful talking to Mary again after all these years about her and Dan with the diagnosis and really that all the emotion of that initial diagnosis and the frustration of trying to get the exact cause of Dan's diabetes recognized really came across, didn't it? Hearing Mary talk makes you feel as a professional how could people not listen when faced with that?

very clear presentation of the problems. But you just worry that as a professional, maybe sometimes you get stuck on a route and going down a particular road and stay on it when you really shouldn't. And I think actually it's okay as a healthcare professional to say, I'm not sure I'm going to go and find out some more, or I need to maybe listen to the family and hear their experiences and...

get some other ideas from colleagues if I'm really not sure what's going on here myself. Yeah, and I think that's such a recurring theme in rare disease. People can't use their experience because often they haven't come across it before, particularly when it's a relatively new discovery as this was at that time. So people hadn't been taught about it. They hadn't seen cases. One great thing was the way it all got sorted out.

And I think really through Mary's persistence that the insulin was stopped and thought the story of testing 48 times was lovely just to show how a thing that was going against everything that Dan had been told that he must stay on this insulin to stay alive and then to realize that that wasn't the case and the way it got controlled by just a quarter of a tablet. Yeah, and to hear the wonderful story of that transformation of Dan's life.

following getting the right genetic diagnosis and changing onto a quarter of a tablet and how he's achieved his dreams of becoming a vet with large animals and now very soon to become a dad himself. Yeah, and for us, Dan will always be important in our talks and almost every talk I give about Modi, Dan is there with his favourite cow. And we're so grateful to you, Mary, for sharing the story with us.

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So join us again in two weeks time when we'll continue the story about maturity onset diabetes of the young.

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