Dr Simon Gibbs, amyloidosis specialist and chair of the Australian Amyloidosis Network, gives an overview of ATTRv, a rare hereditary form of amyloidosis. He explains its symptoms, describes the unmet needs around the condition and discusses the importance of holistic, multidisciplinary care

What is hereditary amyloidosis?

Amyloidosis is a group of diseases where proteins in our bodies misfold or kink, then stick together abnormally to make “amyloid fibrils”, a hard waxy substance, somewhat similar to dried bubble gum, or even concrete. These amyloid fibrils deposit in the organs of our bodies and can stop them from working properly.

The condition is hereditary in about 5% of amyloidosis patients—most commonly these patients have what we call “ATTRv”. The “A” refers to amyloid, the “TTR” refers to transthyretin, which is the misfolded protein, and the little “v” stands for “variant” because patients with this condition have a hereditary variant of the gene for making TTR proteins. Over 100 such variations exist and they make it easier for TTR proteins to misfold and make amyloid fibrils.

ATTRv, which is also known as hATTR (the “h” stands for “hereditary”), affects men and women equally, and it can affect younger people, compared to the non-hereditary forms. Because it is a hereditary condition, other family members can also be affected. That can be psychologically challenging for patients, because they’ve often seen a parent or relative become very sick and possibly die prematurely as a result of the condition. That deep fear of “will this happen to me” is often the first thing we have to address.

What are the symptoms of ATTRv and what impact does the condition have on patients’ quality of life?

Like the non-hereditary “wild type” (ATTRwt) form, ATTRv involves the patients’ heart and carpal tunnels, but it also is more likely to involve the nerves. This means that ATTRv patients are more likely to experience poor appetite, irregular bowel habits, dizziness and weight loss; as well as pain or cramping, numbness, “pins and needles”, burning and “electric shock” sensations in their legs.

When the heart is involved, it can usually still pump okay but it can’t relax properly. This leads to blood pooling back into the lungs, liver and legs, leading to shortness of breath, not being able to sleep properly, significant tiredness, decreased appetite and big swollen ankles.

As the disease progresses, some patients struggle with walking; they may need one or two sticks, or a walking frame. They may also lose muscle strength, become very thin, and have alternating diarrhoea and constipation. So ATTRv can have a great impact on your ability to work and have a social life—it can be really physically disabling.

Is there enough awareness of ATTRv for patients to get an early diagnosis?

Our big passion at the Australian Amyloidosis Network (AAN) is raising awareness of the disease, because without awareness there can’t be early diagnosis—if a doctor doesn’t think about ATTRv, they’re not going to test for it. There’s still such a lack of understanding of the different types of amyloidosis and how you diagnose and best treat the different types.

On some occasions, I’ve had patients come to me saying the first doctor they saw said they could have amyloidosis but there was no point testing because there are no effective treatments. This is completely untrue.

The AAN is about educating doctors, raising awareness that ATTRv is not as rare as you think, highlighting effective treatments, and making it clear that we have specialists who are very interested in this area.

Probably about 80% of people with ATTRv will have some cardiac involvement, so when we were setting up the AAN, we aimed to educate cardiologists about the condition and where patients can be sent for treatment. We gave them tips on diagnosing the condition too. Bone scintigraphy is a scan that picks up TTR amyloidosis in the heart, quite easily and cheaply. But if you don’t know that you can test for the condition in that way, then you’re not going to order it.

Today, when people search for “amyloidosis” and “Australia” on the internet, the AAN website is one of the first things that comes up, so our doctors can easily find information and see where to send their patients.

What are the unmet needs for patients in terms of access to treatment and genetic testing?

By far the most frustrating thing for me, and probably for patients, is access to effective treatments. We have drugs now that we know work—they’re not curative, but they slow things down. But some treatments come at an extremely high cost and patients can’t access them. This is a real cause of angst.

At the AAN we really advocate for our patients—this can be attracting good clinical trials to Australia, pushing compassionate access schemes, and working with pharma to ensure their drugs come to market at a reasonable price, or lobbying government to pay for the medications. Our motto is “Working together, seeking a cure”. When it comes to drug access, I think that working together is key; we need these newer drugs coming along, and clinical trials are really important.

Another unmet need in Australia is genetic testing at a reasonable price. Occasionally we have people saying they want to be tested because a family member had amyloidosis, but those requests are surprisingly uncommon. This might be because Australian patients have to pay for genetic testing themselves. It costs about 400 Australian dollars to test for the TTR gene, but if you know the mutation that your family has, it’s 250 dollars. So we need testing that is either cheaper or, preferably, free. The eight-week turnaround time for tests is another frustration for our patients.

If you think you have a hereditary disease, you want to start treatment yesterday. You want to get on, you want to feel better.

How is holistic care and multi-disciplinary care important in the care of patients, and how do you try and achieve that in your clinical practice?

So much of the management of this condition is about striking the right balance: trying to make the patient feel as comfortable as possible by managing their symptoms, while giving treatment that might slow the amyloidosis down; and that requires holistic, multidisciplinary care.

For example, if the heart is not pumping correctly, your blood pools in the lungs, which causes shortness of breath; in the liver, which can make you sick and puts you off your food; and in your legs, causing swollen ankles. So we need to get rid of any excess fluid you might have, through basic things like cutting back on salt, because salt will make you drink more, and restricting fluids to a maximum of 1.5 litres a day. But, if your nerves are involved so that you feel dizzy when you stand up, we don’t want to dehydrate you too much, because that will worsen the dizziness.

Specialists in amyloidosis are like conductors of an orchestra: you have the cardiologists in the brass section, haematologists in winds, gastroenterologists in percussion and neurologists in strings.

Amyloidosis specialists should have an overarching view, seeing what all the individual specialists are doing. We can advise our patients “here are the basics that you should try” and then refer them to particular specialists for a particular issue.

I always ask patients “if I had a magic wand, what would be the worst symptom for me to do away with?” Because I think you need to find out what’s the most important thing from the patient’s perspective, what’s the most disabling, what’s really impacting on their physical health, their psychological health, and so on, and then address that.

I work primarily at the Victorian and Tasmanian Amyloidosis Service at Eastern Health in Melbourne. We have a local multidisciplinary team meeting once a month where we talk about all of our new amyloidosis patients. We have a pathologist who looks at the biopsies to make sure we’ve got the right diagnosis and amyloid type. We have a radiologist reviewing the patients’ X-rays. We have haematologists, kidney specialists, neurologists, cardiologists and specialist nurses, all of whom contribute to managing the patients’ disease and symptoms as best we can. If we feel a patient would benefit from review by another particular specialist or allied health professional, like a respiratory physician or a dietitian, we’ll refer them on. And we’re increasingly trying to have different specialists attend our clinics. For instance, in our weekly clinic, we now have a dedicated cardiologist who is there especially for amyloidosis patients, helping to manage patients’ fluid problems and heart rhythm problems. That’s just been game changing.

Ultimately, the AAN wants an Amyloidosis Centre of Excellence in each state within Australia, so it becomes easier to know who you can go to if you get this awful diagnosis. And we want to have a multidisciplinary team approach in these centres. Really you need an army of specialists to look after ATTRv patients to achieve the best possible results.

Can you give me an example of an unmet need in holistic care?

One unmet need in holistic care is nutrition. It really is such a key. If the amyloid is infiltrating the nerves that tell your stomach to relax when you start eating, your stomach will never relax and empty fully, and you’ll fill up very quickly. Many patients find that they can you eat maybe most of their breakfast, but then have barely anything for lunch, and nothing for dinner. This is because half your breakfast is still in your stomach at dinner time—it hasn’t passed through as it normally should. So you actually slowly starve and lose muscle bulk. Eventually, you won’t be able to walk. So that’s a major issue and every ATTRv patient probably needs a dietitian to optimise their food intake to ensure that weight loss is minimised.

Patients may also need a gastroenterologist because patients with ATTRv can alternate from having severe constipation, causing pain, to severe diarrhoea. That can really impact on your ability to plan and have a social life. Looking for other causes of bowel problems, like bacterial overgrowth, can be important in managing this, and gastroenterologists are probably under-utilised in helping to manage these symptoms.

Another thing we need to improve on in delivering holistic care is the communication between the amyloidosis specialist, the patient, the carer and the other specialists. That finding came out of a survey of ATTRv patients we did with the help of Mrs. Pat Neely, our patient advocate on the AAN board. Effective communication is about taking the time to talk with patients and being available for them, but it’s also about good communication between the many specialists involved in a patient’s care. A patient might have me as an amyloidosis specialist but also have a neurologist, a cardiologist, a pain specialist, a dietician, and an occupational therapist or a physiotherapist.

What unmet needs are there around psychosocial support?

In Australia we are probably underserved for genetic counselling before or following a diagnosis of ATTRv. It’s a life-changing diagnosis that can be very scary, so there is also a need for psychologists to work with patients and their families.

One of the goals for our network if we had the time and money is that we would like to improve psychological support. Maybe in the future the AAN could employ psychologists one day a week to speak to newly diagnosed patients, or patients and carers in distress.

Part of holistic care is you look after not only the patient in front of you, but the carer sitting beside them. They may feel guilty or worried about passing the gene onto their kids, or who may need to tell siblings that they need to have a test for the condition. Carers often feel really upset that their loved one is so unwell and may feel helpless. We have to acknowledge that this disease also has a profound impact on families.

We need support groups for patients with ATTRv in Australia. Patients benefit psychologically by getting support from each other, and they can also tell us doctors what works and what doesn’t.

We’re encouraging all our amyloidosis patients to become members of the AAN. Then we can communicate more easily about medical breakthroughs, tips on how to manage your symptoms and when we need to advocate to drug companies and to the government. Being a cohesive group can and will make a big difference.

Do you have any final thoughts to share with our readers?

I just want to reinforce the idea of good supportive care often being as important as having access to expensive drugs, at least initially. I will often get newly diagnosed patients to speak with our specialist nurse and with Pat Neely, who is an amazing support to our patients.

I’d say learn about the condition, because knowledge is power; you will feel better if you know a little bit more about your condition, and more in control. However, I direct newly diagnosed patients to reputable websites like ours, or the Amyloidosis Research Consortium (ARC) or the National Amyloidosis Centre in the UK, rather than “Dr Google”. A lot of stuff on the internet is outdated or not relevant to that patient. Patients should also know that they’re absolutely entitled to get a second opinion if they’re not happy or confident with their specialist. Don’t be embarrassed to ask for one.

I would urge patients to get involved and meet other people with this condition. It’s really important to realise that there are other people like you around—you’re not alone.

I would also say that I really think that within 10 years the entire landscape of amyloidosis is going to change. Patients often ask me, “should I test my kids”, and I tell them I’m not so worried about their kids, because I think, in time, therapies will be much more available. I tell them that I’m more worried about their siblings who might be two or three years younger. They’re the ones who should be screened for the gene and if positive, perhaps we need to start treating now, before they actually start showing the symptoms.

Lastly, I would like to reinforce to patients to practise self-care and look after yourself. Don’t be too down or hard on yourself, but reach out for the support that is available, and don’t be afraid to try out new things until you find what’s right for you. Working together with your family, friends and health care professionals in a positive and respectful way can achieve terrific outcomes.

Acknowledgements 

The image of the bone scan is reproduced with kind permission of the National Amyloidosis Centre, London.

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This digital spotlight has been made possible with financial support from Alnylam Pharmaceuticals. Interviews and writing included in these articles have been independently conducted by RARE Revolution Magazine. All opinions are those of the contributors. RARE Revolution Magazine retains all copyright. RARE Revolution Magazine and Alnylam Pharmaeuticals are not responsible for the content of external sites linked to within this article.

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