I’m Heidi Edwards, President and Founder of Sisters’ Hope Foundation, a non-profit organization supporting those affected by adult-onset leukoencephalopathy with axonal spheroids and pigmented glia.
My family has been affected by ALSP for over 20 years. Our ALSP journey started with my Aunt Ruth who was living a normal life of work and family, until one day my family noticed that she started acting differently and exhibiting behavioral changes that led to severe outcomes in her personal life. Her marriage ended, she got divorced from her husband, she couldn’t hold down a job or manage her finances. She ultimately became homeless, wearing torn and tattered clothing, which was totally unlike Aunt Ruth who always presented herself well. Before these changes, Aunt Ruth was a successful sales professional, but during this time in her life she couldn’t hold down an entry-level position. Her life was spinning out of control and none of us could figure out why. It took us two years to get any type of diagnosis, which is not unusual for a rare disease. In the rare disease community, where so much is unknown about the thousands of undiagnosed rare conditions, patients and their families can often spend years meeting with various doctors and other healthcare professionals before zeroing in on an accurate diagnosis.
After experiencing a lot of trial and error, we finally received a diagnosis of Pick’s Disease.
We had never heard of it nor were any of my family members ever diagnosed with it. We were also told that the disease was not hereditary and would not affect any other family members. After her diagnosis our family did our best to care for her at our various homes, but the emotional outbursts and severe mood swings made it too difficult for any of us to offer the type and quality of care that she needed.
Aunt Ruth went to live in a group home care facility, but when her condition became too much for the staff to handle, she went to live in a nursing home until she passed away in 2005, three years after being diagnosed. She was only 56 years old when she passed. We decided to donate her brain to the University of Pennsylvania Brain Bank, and they discovered that she did not have Pick’s Disease, but Binswanger Dementia – yet another disease that none of us had ever heard of. Although we felt that we had a more accurate diagnosis of my aunt’s dementia, we still did not understand why she got sick with the disease and died from it. The doctors reassured us, again, that this disease was not hereditary, none of the other family members would have to worry, and the disease would stop with my Aunt Ruth.
A few years later we started noticing personality changes in my mom. She had become very aggressive, easily agitated and, at times, downright mean. We also began to notice that she had difficulties walking and her walk had been replaced by a slow, shuffling gait. My son, at the age of 4 had started questioning the changes in his grandmother. Not only had her walk changed, but her ability to play with him the way they always did. What he did enjoy were the naps they were now taking together as she was becoming increasingly tired, watching more television so she could relax more often and the extra candy she would give him. My mom would hide the candy from the adults and only give it to the grandkids, secretly, when she thought we were not paying attention. My mother not only hid candy for the grandkids, but potatoes under her bed, tissues in her pockets and pain relievers like Tylenol.
It was at that point that I decided to take her to the doctor at UPenn. Although we were told that the disease Aunt Ruth had was not hereditary, my mom’s illness looked very much like Aunt Ruth’s. The doctors were now certain this was a hereditary condition but uncertain at the type of disease we were dealing with. They did acknowledge that although she was presenting a little different from her sister, they likely had the same affliction. My mom was diagnosed with another condition none of us had heard of and for which there were no treatments or cure: cortical basal degeneration. Mom passed away less than three years after her diagnosis, at the age of 57.
We still had so many questions: Were the diseases, my mom and aunt succumbed to, actually the same disease or different? Hereditary or not? Would other family members be susceptible?
We donated my mom’s brain to the same Brain Bank and upon examination, we were told that she had a type of Alzheimer’s.
In the final stages of my mom’s illness, her brother, my Uncle Chuck, began to have unexplained memory lapses, and became lost driving to work; a route he had driven for 32 years. He had worked for the same company as a mechanic for those 32 years and drove the same route five days a week. All of a sudden, he couldn’t make the trip. He also began to forget how to do many of the functions of his job, a job that he had actually written the “how-to” manuals for. One day on his way to work he pulled his car over to the side of the road, called his wife and told her “I don’t know where I am, I don’t know where I am going. When this happened, we all felt certain that he had “the disease.” By the time we took Uncle Chuck to the doctor he was exhibiting many of the same symptoms as my mom and Aunt Ruth: severe memory loss, confusion and he was often irritable. This disease changes a person’s personality, and the changes are seen very early on. Later on in the disease, he also began to shuffle instead of walk, and like my mother and Aunt Ruth, totally lost the ability to walk. At this time, we were told all three siblings had three different diseases, but at the end of each of their lives, the disease looked very similar. Uncle Chuck’s initial diagnosis was Lewy Body Dementia.
What made Uncle Chuck’s situation emotional was the fact that he had watched this disease take the lives of his two sisters and knew now that it would likely happen to him as well.
I cannot imagine what it must have been like for him knowing that there was a good chance the end of his life would be so horrific. We all knew what he was thinking and could see the anguish on his face and his behavior. At the age of 55 he passed away of this disease, just about the same age as my Aunt Ruth and my mother.
The doctors at UPenn agreed that the similarity in the symptoms across the three siblings made it hereditary. It was definitely a type of dementia, and they were challenged to understand which of the 32 dementias known to the medical profession this was. The fact that it was perplexing to the doctors at UPenn made it even more puzzling to my family.
Shortly after my uncle’s death, the UPenn neurologists who had been following my family’s story requested a family meeting. They informed us that Uncle Chuck’s autopsy had identified the mutated gene affecting our family: the CSF1R gene. The doctors reexamined the brain tissue of my mother and Aunt Ruth and determined that they, too, had the CSF1R mutated gene like my Uncle Chuck. This mutation pinpointed the condition as Hereditary Diffuse Leukoencephalopathy with spheroids, now known as ALSP. We finally had an exact diagnosis.
CSF1R is an autosomal dominant gene which means that a child of a parent who has the gene has a 50% chance of inheriting the gene and contracting the illness. My mother has nine siblings and 3 of the 9 became symptomatic and passed away from the disease. I am one of three sisters. I have always been one to believe that knowledge is power. Therefore, after learning about the CSF1R mutation, I chose to get a predictive genetic test and it was negative. I was relieved but also felt a giant sense of responsibility. My older sister Heather and my twin sister Holly chose not to get tested. Unfortunately, both of my sisters started exhibiting symptoms shortly after my Uncle Chuck passed away.
I started noticing my sisters’ minor symptoms first and I documented them. By the time their symptoms became obvious, Heather could no longer hold down a job, was unable to manage her finances and would overspend. She also exhibited something that was unique to any of the other family experiences and was unable to translate her thoughts or words into a logical text message. The words would come out of her mouth just fine, but what she would text was jumbled and would read as gibberish. She also began to exhibit problems with her balance and showed perception difficulties when she tried to drive the car. This became acute when she mistakenly put the car in reverse instead of forward; nearly putting her car, boat, trailer and family into the water.
Around the same time, Holly was beginning to decline too, and she was mixing up words and transposing letters from one word to another. Unlike Heather, who could talk, Holly was losing that ability. As dire as this situation was, I guess you could say that there was a silver lining in all of this. Living through what my Aunt Ruth, Uncle Chuck and Mother experienced, we understood what was happening with my sisters.
We were presented with an investigational treatment option of bone marrow transplant, and we chose to pursue it for my sister, Heather. Since I was the only sibling with a negative confirmation from genetic testing, I was tested to see if I was a match. I found out on my birthday that I was a 100% match for her: my sister’s genetic twin.
Since the bone marrow transplant occurred during the pandemic, we were not allowed to visit Heather during her hospital stay at the University of Minnesota or on the day of my sister’s transplant. All of us watched Heather receive my bone marrow over a Zoom call and were excited at the prospect that this might just help my sister. Unfortunately, our hope was short-lived as 15 days after the transplant Heather suffered a heart attack. We were told that the chemotherapy plus transplant would progress the disease before halting it; which it did despite Heather’s overall good health and strength.
The incident put her into the ICU where she was placed on a ventilator, had a feeding tube inserted and lost the ability to move and speak. Despite the complications we were still hopeful that she would be able to accommodate the bone marrow into her body. Unfortunately, Heather began to reject the bone marrow which meant that she needed to receive platelets every two days while continuing to remain in the hospital. Her condition continued to worsen and Heather’s husband, Eric, decided to put her on hospice for whatever time she had remaining, which as it turned out was not long. Heather passed away in August 2020 at the age of 45.
Meanwhile, Holly had a seizure during this time and was diagnosed with ALSP. Her condition continued to worsen, and she began to show signs of an advancing dementia. By this point, we could not understand the words she was saying. Right before Heather’s death, Holly was scheduled to begin her own bone marrow transplant. At this point she had lost much of her ability to function physically and is in a steep cognitive decline. Our concern, as her family, was that she would experience the same challenges as Heather and in the end all that pain, frustration and anguish would be for nothing.
As a family, it was important that we helped Holly make the best decision possible, but because of her condition it was almost impossible to have her understand the complexities around these end-of-life decisions. Of course, when you live through multiple losses of life due to a rare disease that had been fatal with each person, these types of conversations with family members who are not ill, are fairly commonplace. We knew quite well what Holly’s wishes were and it wasn’t to die alone in a hospital, 1000 miles away from home.
We decided to cancel Holly’s procedures and brought her home to live out the rest of her days surrounded by her family. Holly passed away on July 20, last year at the age of 44.
During her final days our family and friends made lovely memories with her. Nothing was out of the question and whatever she wanted to do; we did. We took her on road trips to the beach and carried her onto the sand so she could be close to the water, we held celebrations at her house and enjoyed each remaining day.
I started the Sisters’ Hope Foundation to honor my sisters, raise awareness and education of ALSP, and to connect people affected by this devastating disease. Since there was so little information available about ALSP for my family, it is important to me to link patients and families with expert neuroscientists who understand the complexities of this disease and to give them hope that they are not alone in this journey.
I encourage you all to share your story. Every story is important and should be heard. You are not alone in your journey with ALSP.