My life with Dutchype CAA

Last week I was asked to contribute to a Alnylam's seminar about 'patient perspective'. Could they kick off the meeting with me telling my story? About my life with Dutchtype CAA? The words 'patient's perspective' means something different in the context of a genetic disease. Sporadic diseases happen to you, genetic diseases are predictable and influence your life long before any symptoms show. So, I wrote a part of my story, and my motives for advocating for DCAA family members, down. And then I thought since one of my goals is to raise awareness, I should use it. It is hard to capture all the complexities of DCAA in a short story, but I tried. Here we go.

My parents started the DCAA patient association in 2007 after my mom’s test result came back positive. During her psychology master’s program, she interned at the clinical neurology department at the Leiden hospital and witnessed the importance of patient associations for other neurological diseases. She wanted to use her experience as a psychologist and her lived experience to improve the lives of all DCAA family members.

For those who don’t know: the mutation for DCAA originates from Katwijk, dating back to at least 1700, and most DCAA family members still live there. People from Katwijk are what we call ‘honkvast’ (they tend to stay in the same place) because Katwijk is a great place to live, and most of my family members still reside in the town. There are also a number of families in Scheveningen, the next town over, which is also a fishing town with close connections to Katwijk.

So, most families live in Katwijk or Scheveningen, but we are aware of families all around the Netherlands and the world. During and after World War II, several families moved to other parts of the country and the world. To Australia, for example. That’s where the Plug family lives; they migrated from IJmuiden in the ‘50s and referred to the disease as ‘the Plug thing’ for a long time because they didn’t know anyone else with Dutch-type CAA. It's also where two other families live. Who knows how many are out there we don't know of, yet? People moved, and men from Katwijk travelled places being fishermen...

DCAA was ‘discovered’ by a GP from Katwijk, Timmers, and a neurosurgeon from the Leiden hospital, Professor Luijendijk. They noticed that many people from Katwijk died of brain hemorrhages and decided to study family trees. From my ability to visit the archives at the Leiden hospital, I learned that my grandfather participated in that first study that described his (my) family.

My grandfather, Cornelis de Vreugd, came from a family of 10 brothers and 1 sister, of whom at least 8 died of a stroke. Considering their offspring, my family alone accounts for dozens of patients and deaths.

My grandfather died in 1967 when my mother was 7 years old, at the age of 53. By that time, he had been sick for at least two years and had been sleeping downstairs. My mother lived with other family members for a significant part of her youth. She was with the neighbors on the other side of the street and realized her father had died when she saw the curtains being closed in the middle of the day.

Although my mother and her siblings knew that there was probably something genetic going on, they did not have the awareness we have today. At that time, people were afraid but also felt there was nothing to be done, and most were not focused on being at risk.

That changed when, in 1995, my oldest aunt Corrie died suddenly at the age of 55. By that time, awareness had also grown because they had identified the mutation causing DCAA, and genetic testing was now available. My mother’s other three remaining siblings, along with her and my aunt’s kids (who were the same age as my mom), began to truly feel the grim reality of potentially suffering the same fate.

My aunt’s death and not having a grandfather meant that by the age of 5, I was very aware of the disease in our family. My life has always been affected by it.

When my mother reached the age of 45, she decided to get tested for several reasons. My older sister was getting married, and she wanted her to start her life possibly free of fear. She also felt that her fear of becoming a patient was weighing heavier than the hope of not becoming one. She knew her father had only been 53 and her sister 55 when they died, and she wanted to live her life differently if she also had a few remaining years to live.

While she was waiting for her result, my aunt’s daughter, a few years younger than my mother, suffered her first hemorrhage in her early 40s and was on the verge of death. When that happens, multiple things occur simultaneously. You worry about your family member, feel anger because DCAA strikes again, and are automatically confronted with a future that might be yours. The dynamics of a hereditary neurodegenerative disease are very hard to explain.

Unfortunately, my mom’s test came back positive, which meant a huge life shift for her, my father, the four of us, and our partners.

We were not allowed to tell my grandmother, who was over 90 years old at the time, that my mom was a gene carrier. She had already experienced too much sorrow in her life, having survived three of her five children (my aunt died of DCAA, my uncle died of a heart attack, and my other aunt’s cause of death was unclear). Being the partner of a gene carrier (as my grandmother was) and losing your partner and children is incredibly difficult.

We have always been close as a family, but we started to enjoy life with each other more. We did the things my mother always wanted to do, saw the northern lights, and made sure everything that needed to be said was said.

It was also very scary. I was 16 at the time. Would my mom make it to my high school graduation? Would she be there for my bachelor’s, my master’s? Would she be there for my wedding, for having kids? I panicked every time I heard an ambulance in town. I once searched the house when her car and pushbike were there, but she was nowhere to be found. It turned out she had gone to the supermarket on foot. I called my father in a panic at 4 AM because he had called me a few times. It turned out I had been butt-dialing him the whole night while being slightly drunk.

Going back to the patient association and our ‘why’: DCAA has been known since the ‘60s, but there was a lot of misinformation and taboo surrounding it. Additionally, research pretty much stopped after the ‘90s because we turned out not to be ‘a model study for Alzheimer’s.’

When we started the patient association in 2007, it began with a small article in the local paper announcing a meeting for DCAA family members. 45 people showed up. Our goals were to provide better information to families, to eliminate the taboo (one factor influencing the taboo was the story circulating that the disease was a result of inbreeding), to organize peer support groups and expert meetings, to help establish better healthcare, and to initiate research (and find a treatment).

A few years after our initiative, DCAA became ‘a model for sporadic CAA,’ and we started working with Professor Greenberg at Harvard. Although we were very happy that this opened up new opportunities, the enthusiasm about ‘being a model for sporadic CAA’ was sometimes hard to process. We hated being a model for anything. We hated DCAA and everything it did to us.

My mother was our chairwoman for over ten years but felt her health declining. She also had to leave her psychology practice, which ended in a (financial) conflict with her colleagues and was very stressful at the time. There was no goodbye party, no retirement drinks—just conflict. A few days later, she had her first major stroke.

She woke up feeling strange and had trouble speaking. She tried to hide it from us so as not to worry us, but it was very obvious that something was wrong. She went from someone who had very strong verbal skills to someone who had trouble finding words. The speech therapist who started helping her sent her home after a few sessions, impressed by her remaining vocabulary.

Although we could see signs of cognitive decline, she did not have any major events for a long time. She visited the neurologist every year or so and participated in natural history studies to help advance science. Two more major bleeds and many microbleeds were detected on scans, but we were never in a crisis situation.

By this time, she has far outlived her family members. We were surprised to see her reach 60 and will celebrate her 65th birthday in a few weeks. Over the years, we have seen her change from a smart, confident, independent woman to someone who gets overwhelmed in social situations, sometimes forgets how her phone works, has trouble doing simple things like cooking a meal, and occasionally becomes angry and frustrated. Her world is getting smaller and smaller, and it is sometimes hard for her to maintain her self-worth.

My role as a daughter has changed as well. I try to help as much as I can, although she is very proud and finds it hard to let others in or show that she needs help. The past two weeks, we had no other choice.

Two weeks ago, my father woke up to my mother screaming in pain. She was cramped and unconscious. He immediately called emergency services, who guided him through what to do (opening up airways, etc.) and were there within 5 minutes. They suspected an epileptic seizure—and they were correct. A medicinal treatment through IV brought her back in the next hours, and she was allowed to leave the hospital.

I moved back in with my parents for a while to help care for her. She would have episodes 8 times a day, forgetting how to do things like showering and brushing her teeth. For the first few days, she didn’t remember anything we told her.

It was a glimpse into a possible future of the disease claiming her and us. It is one of her worst fears, and ours. Sometimes we feel it would be better to die all at once than to slowly decline into someone who depends on others for everything.

Fortunately, now that she has been on medication for a week and a half, she is gradually getting back to her old self, even being a smartass about things my dad and I forget from time to time.

That doesn’t take away from how scary the disease is and what the future may hold. Being part of the patient association and being a family advocate means meeting many, many DCAA family members and hearing their stories. Although I love being able to support them, it can also be confronting and frightening.

The disease takes so much away—so much freedom and joy. The chance of retiring and doing all the things you wanted to do, the chance of seeing grandchildren grow up. And then there’s the possibility of becoming "a burden" on your partner and children. There's also guilt over passing the gene to your children...

I think about undergoing genetic testing a lot, but until now, it hasn’t felt right. There are many intellectual considerations that can go into the decision to get tested or not (money, partner, children, preparation, health management), but for me, it is mostly a gut feeling. Right now, I live my life as if I carry the gene, not postponing anything I really want to do or accomplish in life. If I happen not to carry the gene, I will enjoy my “bonus years” as much as I can. The possibility of a “bonus” comes closer as I get older. I am 36, and some family members had their first stroke in their early 40s…

So, I continue to fight for all DCAA family members. We have come such a long way, and yet there is so much more to accomplish. I hope to one day look back and see how much it was worth spending my precious time. And who knows, I might turn our story into a book. I might find the time.

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