The Adelaide based Rare Find Foundation, created by bereaved parents Anna Pak Poy and Marc Coupar, is on a mission to fight Tay-Sachs and Sandhoff diseases, rare genetic diseases that until now have mostly gone unnoticed by families until it’s too late. UniSA journalism lecturer Dr Ron Hoenig uncovers the consequences of this devastating disease that primarily affects young children, who have tragically lucked out of the genetic lottery.
By Ron Hoenig | @ronhoen
The home page of the Rare Find Foundation (RFF) features pictures of beautiful children, their faces marred by little plastic tubes running up into their noses, with bandages sticking the tube to their faces.
At the extreme right is a cherubic little boy with reddish curly hair and clear, searching bright blue eyes. He is Sebby, the son of Anna Pak Poy and Marc Coupar.
Sadly, Sebby is now dead. He died at 22 months in March 2019.
He is a victim of Tay-Sachs, a genetic disease that is killing children very early in their lives – against the odds.
“He would touch people in the most extraordinary ways,” Anna says.
At his funeral, Anna’s sister said: “Sebby went around just collecting people like they were treasures and putting them in his pocket and that’s where they stayed.”
Anna is the founder of the RFF, which supports parents whose children have died from Tay-Sachs and Sandhoff diseases, for which there is currently no cure.
The diseases are buried in parents’ own genetic history – and in many cases, they have no idea where or how. Most affected parents have never heard of the diseases before but will never forget them once their child becomes a victim.
Anna’s guarded eyes only once give way give to the terrible sadness of losing a very young child. An experienced interviewee, she says she usually toughens up.
“What I have to do is take off my Sebby’s mum hat and put on like an almost a commercial hat because I can’t just sit here in tears every time I talk about it,” she says.
Not this time. This time she weeps.
We’re on the rooftop garden on the upper floors of the city office building which houses the office of the foundation as well as two head-hunting consultancy businesses Anna runs.
We’ve both bought coffee, but she is not drinking. There’s a fair breeze blowing, so she speaks loudly, quickly and precisely as if she’s dictating it against the wind.
We both know grief has a way of breaking through the cracks in conversation. I am here asking how it is to be the mother of a child who has died of a “brutal”, rare, incurable genetic disease and she knows I am dealing with the grief of recently losing my wife of forty years.
“When you talk about it in certain situations and particularly one on one without a television camera or a microphone, sometimes it is very personal, so and it brings it to the surface…”
There’s a lesson here for me, too – not only about grief.
Tay-Sachs is named after the ophthalmologist, Warren Tay and neurologist Bernard Sachs who described the disease in the late 19th century. Sandhoff is a German biochemist who recently described the disease process.
Tay-Sachs and Sandhoff are very similar, but there are very strong ethnic connections in Tay-Sachs whereas in Sandhoff that don’t seem to be any ethnic connections and the liver swells. Both diseases attack the nerve cells in the brains and spinal cords of very young children. Think of the nerve cell as a system which does vital communication work in the body but creates junk as a by-product. The junk is called gangliosides or GM2. If GM2 isn’t cleaned away, it accumulates and eventually overtakes and destroys the cell.
Typically, an enzyme called the Hexosaminidase A (Hex-A) breaks down the GM2 in a cell. Hex-A is created outside of a cell and is normally absorbed into it, but Tay-Sachs and Sandhoff sufferers don’t produce enough (or any) Hex-A enzyme. The GM2 then accumulates in a place in the cell called a lysosomal storage area (LSA) and eventually destroys the whole cell.
As a result, children’s development regresses at about six months and they suffer infantile dementia, becoming unable to roll over, move or crawl. They then suffer seizures, hearing loss and eventually die.
The most common form of both diseases is infantile when the symptoms hit between the third and sixth month of the baby’s life. In the juvenile form, the symptoms hit later in children’s development and children die sometime between 10 and 15 years old. The diseases may also have a late onset when the person is in their mid-30s. Then it’s not usually fatal but it is very physically debilitating.
Like many people on a mission, Anna has severe issues with work-life balance. She actually has four jobs – running two businesses, driving the fundraising and support activities of the foundation and now mothering Layla, her second child, who represents a rare win in the roulette wheel of odds for parents who are carriers of these genetic diseases.
When two carriers produce a child, they have a one in four chance of creating a child who will be stricken with the disease, two chances in four of giving birth to a carrier of the defective gene and one chance of a child with no copies of the defective gene at all. A CVS scan of Anna’s placenta when Layla was in utero showed she had no copies of the gene at all and she was born perfectly healthy in August last year.
The diseases are considered rare because they occur in one in 180,000 births or in the case of Sandhoff, one in 300,000. In the general population, the number of carriers is one in 250 people and the chances of a carrier having a baby with another carrier are reassuringly small – but not impossible.
In the case of Tay-Sachs, however, if you belong to certain ethnic groups – if you happen to have Amish, Irish-American, Cajun or French-Canadian genetic inheritance – your chances of being a carrier increase six times to one in 50.
But if you are an Ashkenazi (central or eastern European) Jewish person, as I am, your chance of being a carrier increases again to a concerning one in 27.
Like Anna and Marc, I have taken the 23andme genetic test because my grandparents on both sides were killed in the Holocaust and I want to track down lost family members, particularly on my mother’s side. The test involves spitting into a tube and sending it off to the US-based personal genomics and biotechnology company for processing. According to the results, I happen to be 99.7% Ashkenazi Jewish.
In Britain, where Anna and Marc took the test, and many other countries, the commercial firms ask you if you want to know your genetic health history.
Anna asks me if I requested information about genetic health. “I opted out,” I say, and she says that at first, so did she.
Actually, I didn’t opt out. I had no choice. 23andme does not provide a genetic health testing report in Australia as it does in the UK. I recently asked them to provide a genetic health scan and they responded: “regulatory bodies in your region may have requirements that prohibit or fundamentally change specific reports or products”.
Then Anna tells me how she and Marc found out that that they had lost out over some very high genetic odds. I sense she’s told the story many times.
Both of them have very diverse backgrounds. “I’m like part Chinese. I’m part Jewish. I was born in Australia. I was living in the UK. I knew I had Scottish. I knew I had Irish. My husband: he’s Scottish-born and he’s a quarter Nigerian. He’s got French … so purely for genealogy intrigue, we did the test with 23andme.”
Marc opted to receive the health report.
The test revealed he was a carrier for Tay-Sachs, but he’s in the general Caucasian population, which meant that he had a one in 250 chance of being a carrier.
“So we didn’t know what Tay-Sachs was and we looked it up and we saw that actually it affects children. Symptoms start to show when the child is six months old. And we’ve got a six-month-old boy and then we also saw that actually it has a higher frequency rate in Jewish populations. And we knew categorically already that I did have Ashkenazi Jewish (background).
“I then, of course, changed it to see my health report and then I saw that I was a carrier as well, which then meant that Sebby had a one in four chance of being affected.”
Anna and Marc went to a genetic centre in London and had to replicate the tests, which confirmed they were both carriers and then they tested Sebby, knowing that he had a one in four chance – “and sadly, and I’ll never forget this day – it came back showing that he was affected”.
“So, statistically, it went from being something we never knew about to … Marc then was a carrier (he’s got the least chance of being a carrier but he was a carrier) and then me being a carrier. It just got slimmer and slimmer until we found out that Sebby was affected.”
I can’t help reflecting. Genetically, I am almost completely Ashkenazi Jewish. Am I a carrier? I’m 70. I’m not planning to father any more children. My wife was half English and half Irish. But my daughter is 37 and has two beautiful children beyond the age when Tay-Sachs usually shows up. What about my grandchildren? Are they carriers? Could they meet someone in the future who is also a carrier? Their dad belongs to the general Caucasian community. One in 250 versus one in 27 in my case. What are the odds?
Anna had lived in the UK for 10 years but was originally Adelaide-born. Marc was born in Scotland. For family support, geographic convenience and global expert medical care from Dr Nicholas Smith, the current head of Neurophysiology at the Women’s and Children’s Hospital, Anna and Marc decided it was time for their little family unit to come to live in Adelaide. They arrived in April 2018, when Sebby was 11 months old. He had just started showing symptoms of reversal.
“If we were to look back at the silver lining on receiving the diagnosis in the way that we did, it’s that we were able to locate back to family and support and to be close to globally-acknowledged expertise,” Anna says.
It could have been very different. If Sebby had not hit developmental milestones and shown symptoms, they would have waited and investigated and then have gone through the process of elimination up to genetic testing much later.
“It would have been anywhere between unrealistic and cruel to have relocated,” she says.
The Rare Find Foundation aims to help affected families to know there is support for them. Anna is its chair and its board includes Dr Smith, former ALP member Kate Ellis, CEO of Parkinson’s SA, Olivia Nassaris and long-time charity worker Kristen Alderson.
“I’ve spoken to a lot of bereaved families in Australia and sadly there’s many similarities in how they’ve received their diagnosis because there was no existing charity here,” Anna says.
RFF’s first priority is to develop an information pack – in hard and soft copy.
Hard copy, she says, will save couples reading in clinical language what their children will face.
“We’ll be providing them with information instead of them being given a piece of paper with Tay-Sachs or Sandhoff written on it which leads you down a rabbit hole of academic research papers with blunt prognoses and symptoms.
“It’s horrible,” she says. “That’s not a way a family should discover that they’ve got a child that’s going to die.”
Parents will be able read through the information at their own pace and will also find more detailed information within the online resource that the foundation will create.
The pack will include a signed letter from the foundation offering support.
“It’s so when you walk out of the metabolic or neurologists specialist room or the genetic counsellors in the children’s hospital in your state you’ve got something there with a signed letter from the foundation so that you know that there’s people standing next to you.”
Parents can also share “clinically correct but sensitively toned” information with family members who may not be technologically savvy.
Anna says in some ways people diagnosed with Tay-Sachs or Sandhoff disease are worse off in Australia than if they were diagnosed in another developed world region.
Up until last year, there was no charity and there is still no disease registry, which is the foundation’s next priority.
No one knows how many Tay-Sachs or Sandhoff patients there are in Australia because there is no disease registry. Without a disease registry, there are no pathways for children’s health centres in the states to reach out to one another.
Not having clear numbers and knowledge of patients across the country means that children can miss out on life-altering research.
“When there are clinical trials globally, patients here miss out,” Anna says. For example, currently, in the US there are two children that have been dosed with gene therapy for trials and of course they have to fit specific criteria. “But because there is currently no national disease registry here we don’t know if we have anyone who fits the criteria.”
The foundation will also be helping to fund research.
“We’re in the year 2020 and of all the remarkable technologies that are available and that have been developed,” she says. “… and my child has just died from a disease that has been known about for a long time and that is absolutely devastating.”
Anna points out one of the disconcerting repercussions of the 21st century’s more diverse multicultural world. In the past, people tended to have children with people of the same or similar genetic inheritance. As a result, there were some diseases, like Tay-Sachs, that were limited to particular ethnic groups. But now, people are meeting and finding love with people whose genetic inheritance is vastly different from themselves and people are less likely to know the full details of who their ancestors were.
She advocates genetic testing for everybody. Now that genome sequencing is relatively cheap and generally available, and people are making “informed and responsible choices” about when in their lives and careers they are having families, she thinks “a crucial point in being responsible in procreating is having a genetic test”.
The foundation is also hoping to raise awareness among GPs of genetic testing of pregnant couples.
A $20 million government genetic testing initiative started this year spurred on by McKenzie’s Mission, a movement started by a parent couple, who lost their child to SMA (Spinal Muscular Atrophy) at the age of seven months.
As part of a pilot program, there are now 10,000 free genetic tests available to couples in Victoria, Western Australia and New South Wales. If it’s successful, the program will then open in other states and territories.
What will couples do who find out they are both carriers? They will have to make huge choices.
“At least they will have information,” Anna says.
Meanwhile, I am continuing research to find out if I am a carrier.