Refsum: A rare disease hiding in plain sight

Sharon Burstin is on a mission. For 51 years she lived with a disease she didn’t know she had, as it slowly and irretrievably stole her health.
 
At age 54, Sharon is now legally blind and walks with a white cane. She has hearing loss, has endured severe osteoarthritis and subsequent knee replacement surgery. She also lives with paraesthesia, polyneuropathy and anosmia.
 
It is with a combined sense of urgency and frustration that Sharon now speaks about Refsum disease, the condition she was finally diagnosed with in 2022, at the age of 51.  
 
‘No one has [heard of Refsum] and that’s something that just drives me crazy,’ she tells newsGP.
 
‘It’s basically what has motivated me to really push for awareness because there’s a lot you can do if you’ve got Refsum to slow down the progression.
 
‘I could have slowed down the progression sooner, and that would have made a really big difference to my life.’
 
Refsum disease is a rare metabolic disorder. It affects around one in a million people in the United Kingdom, but its prevalence in Australia remains unknown.
 
It is caused by several faulty genes that prevent the body from metabolising phytanic acid, allowing it to build up to toxic levels in the body’s nerves, blood and tissues.
 
Phytanic acid is found in many foods, including dairy products, red meat and fatty fish. It is also derived from phytol, a component of chlorophyll in green leafy vegetables.
 
In a person with Refsum disease, the effects of phytanic acid build-up in the body can be catastrophic and irreversible.
 
Refsum can affect a person in different ways, but retinitis pigmentosa (RP) is the most common symptom. Other symptoms can include lack of pupil dilation, deafness, cataract, ataxia, anosmia, ichthyosis, peripheral polyneuropathy, general weakness, heart problems such as cardiac arrythmia, and skeletal dysplasia.
 
Sharon ticks the box for nearly all of them.
 
So, for most of her life, she saw myriad specialists to treat her many ailments, such as ophthalmologists for her loss of vision, audiologists and ear, nose and throat specialists for hearing loss, ear pain and anosmia, and orthopaedic surgeons for her skeletal dysplasia.
 
All the while, as separate clinicians treated Sharon’s conditions in isolation, Refsum disease was hiding in plain sight.
 
‘There was definitely anger that no one had joined the dots sooner, seeing as I had so many of the symptoms,’ she said.
 
Although it’s not a symptom that affects all people with Refsum disease, Sharon had the first signs of it the day she was born – skeletal dysplasia.
 
The first and last digits on her hands and toes were abnormally short compared to the middle three.
 
She had corrective surgery when she was 11 to reduce the length of her second and third toes to make walking easier, but they remain much longer than the rest.
 
‘When I went for the operation on my feet, [the surgeon] didn’t say, “is there anything unusual about your sense of smell or your vision, or your anything?”,’ said Sharon.
 
‘He just saw these feet and said, “they’re unusual, too many bones here, not enough bones there, we need to play around with it, blah, blah, blah”.’
 
From her late 40s, Sharon saw many more orthopaedic surgeons for the severe osteoarthritis she had also developed, but still none thought to further investigate why she had developed the disease without any of the usual causes such as overweight or injury.
 
Around the same time as her foot surgery, Sharon was diagnosed with RP, a group of inherited eye disorders that can cause various types of vision loss, from night blindness and loss of peripheral vision to total blindness. An incurable disease, it affects about one in 4000 people worldwide.
 
RP is also a key symptom of Refsum disease. But no one knew to investigate further.
 
‘If I would have had a phytanic acid test done then, that would have been very helpful,’ says Sharon.
 
And in a cruel twist, the recommended diet for people diagnosed with RP can be toxic for those with Refsum disease – phytanic acid-rich fatty fish and leafy green vegetables, especially kale.
 
Sharon’s childhood diet was, in short, a Refsum wrecking ball.
 
In addition to the RP diet she was following, she was also consuming high amounts of dairy products – which are also rich in phytanic acid.
 
‘I basically was a milk and cheese girl,’ she said. ‘I was quite a fussy eater at that age, and all I liked was cereal with milk and sandwiches with cheese. I was having so much dairy – my favourite thing was pizza with double cheese.
 
‘If I had have known then to cut out dairy … but I didn’t until I was 27.’
 
Sharon must now follow a strict diet that governs not just what she eats, but when, to prevent her body from producing phytanic acid.
 
‘I had put myself on a superfoods diet when I was 27, to try to stay as healthy as possible,’ she said.
 
‘Unfortunately some of these superfoods are terrible for Refsum, but at least I was used to following a restricted diet. I just had to adapt it.
 
‘What was harder for me was changing the way I eat, like eating before exercise, and eating regularly throughout the day.
 
‘It’s important that you’re not burning fat at any stage of the day, because that’s what makes your body produce phytanic acid. So, you’re not supposed to ever get hungry.’
 
Last year, Sharon was the subject of a research paper, titled Forty-year odyssey to Refsum disease diagnosis.
 
Part of the research includes a retrospective review of 23 patients with the condition. The patients had an average delay of 11 years between initial presentation to an eye care practitioner and receiving a diagnosis of Refsum’s. And all 23 had RP.
 
It is RP that should be a red flag to any GP to warrant further investigation for Refsum disease, which can be as simple as an initial blood test for phytanic acid levels, said Sharon’s GP, Dr Vicki Kotsirilos.
 
‘As GPs, if we’ve got patients with [RP], we should suspect Refsum’s and have it tested,’ Dr Kotsirilos told newsGP.
 
‘It may not be the case [that Refsum’s is present], but it could be, and it was the case with Sharon.’
 
Sharon’s diagnosis finally came after she was referred to take part in the VENTURE study at the Centre for Eye Research Australia, in an effort to find the cause of her RP.

After the genetic findings, a genetic counsellor confirmed a diagnosis of Refsum disease, and then referred Sharon to a metabolic doctor at the Royal Melbourne Hospital. She has been under their care ever since.

It is a source of frustration for Sharon that a simple blood test after her Refsum diagnosis confirmed what had been there all along.

‘Blood phytanic acid levels are meant to be 0–3.5. My first one was 450,’ said Sharon.

‘If only I had had that blood test when I was first diagnosed with RP, my whole life trajectory would have been completely different.’
 
Dr Kotsirilos is one of Sharon’s biggest supporters, helping her to raise awareness of Refsum disease – which, like most GPs, she had never previously heard of.
 
‘In medical school, we were only taught about common genetic disorders, like Down syndrome, Turner syndrome, trisomy, cystic fibrosis, but we were never taught about Refsum disease,’ she said.
 
‘The symptoms are often not recognised as being part of a genetic disorder, so they’re often treated on their own, but when you start to piece it together, it’s like a jigsaw puzzle, it all then starts to make sense.
 
‘Had the condition been detected earlier and she was placed on the [correct] diet, that could have actually slowed down the progression of the disease.’
 
Sharon’s diagnosis has united her with a small but passionate global Refsum community. Earlier this year, she hosted a webinar with the US-based DARE Foundation (Defeat Adult Refsum Everywhere).
 
It was the first time she had spoken in public about the disease – and she nailed it, said Dr Kotsirilos.
 
‘It just came naturally, Sharon explained everything so articulately,’ she said.
 
‘This is why I’m so proud of her, because there’s a part of her that understandably feels a bit angry … she’d been seeing different specialists for her different conditions. This is even before she saw me.’
 
Sharon said she is ‘channelling the energy I’ve got around that anger’ into raising awareness of Refsum disease.
 
She wants all GPs to know that a diagnosis is within their scope of practice, through a simple blood test for phytanic acid levels.
 
She also urges GPs to watch the webinar she did with the DARE Foundation, and spread awareness through their networks of specialists about Refsum.
 
‘I’m hoping that my awareness raising does help people,’ she said
 
‘I could have had a completely different life. But I basically thought, “what a difference it would have made to get an early diagnosis, and what a difference that could make to other people”.
 
‘Awareness will raise the chance of diagnosis exponentially, and ensure people get the life they deserve.’
 
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acid anosmia blindness disease disorder genetic hearing loss metabolic phytanic rare Refsum vision