Wednesday, September 3, 2014

The diagnosis

August 22, 2014 - I was getting in the car to drive to our nearest temple which is 2 hours away. Brad was planning on staying home with the kids, so he had already left to go to the park. As I sat in the car ready to leave, I thought about the fact that by the time I got to the temple and did my service, it would be 7:30 or 8:00pm and I was feeling very tired. I wondered if it would be a good idea for me to go and drive home when I was already feeling so exhausted. I changed my mind and decided I would schedule a time to go early in the morning with less risk involved.
I came back inside and started to clean my house. Shortly after, Dr. Aleck (a biochemical Geneticist we had seen in Phoenix, Arizona) called me. He said "I have a diagnosis for your two boys, but it isn't too good." I felt excited that we would have a diagnosis and then, "but wait, not Evan too?" He told me they had Gm1 Gangliosidosis late-infantile type, based on the age of onset, probably not the juvenile type. He had to spell it for me as I wrote it down. He explained to me that it was a genetic disease that would only manifest when both parents had the recessive gene and passed it along to their children. With each pregnancy you have a 1 in 4 chance of a child manifesting the disorder. He said Laya was most likely a carrier. He told me that Eli is unable to process a certain Enzyme, so his body stores that enzyme in the spinal chord and brain. Over time it builds up and causes nerve damage.
I asked him what it all meant. He said, "In terms of prognosis, it is unlikely that he will make it to adulthood." I paused and my heart sank. He told me he was so sorry that he had to give me this news over the phone. He explained that he thought Evan had it as well and told me we would need to prove it through DNA for both of them, although he was confident in his diagnosis about Eli.

 I proceeded to search the internet and cry and search the internet and cry. Here's some of what I found. 

GM1 Gangliosidosis falls under the following categories: 

Lysosomal Storage Disorder
Genetic Brain Disorder
Inborn Error of Metabolism and Metabolic Disorder

What is it? GM1 gangliosidosis is an inherited lysosomal storage disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. Some researchers classify this condition into three major types based on the age at which signs and symptoms first appear. The three types include: classic infantile (type 1), juvenile (type 2), and adult onset or chronic (type 3). Although the three types differ in severity, their features can overlap significantly. Because of this overlap, other researchers believe that GM1 gangliosidosis represents a continuous disease spectrum instead of three distinct types.

Some Signs and Symptoms of Type II Gm1 Gangliosidosis which begin between the ages of 1 and 5.
* Ataxia (Uncoordinated movement is due to a muscle control problem that causes an inability to coordinate movements. It leads to a jerky, unsteady, to-and-fro motion of the middle of the body (trunk) and an unsteady gait (walking style). It can also affect the limbs.)
* Seizures (Eli has had no seizures that we know of)
* Dementia, (Dementia is a loss of brain function that occurs with certain diseases. It affects memory, thinking, language, judgment, and behavior.)
* Difficulties with speech (One characteristic of the late-infantile verses juvenile is that the late-infantile usually don't develop speech, juvenile can often speak pretty well, but then lose that ability. Both Eli and Evan have not developed understandable speech)
* Type 2 typically presents at age 1-2 years with progressive psychomotor retardation.
* Little visceromegaly (is enlargement of the internal organs in the abdomen, such as liver, spleen, stomach, kidneys, or pancreas)
* milder skeletal disease are present compared to the infantile form.

What causes Gm1 Gangliosidosis? Mutations in the GLB1 gene may decrease or eliminate the activity of the β-galactosidase enzyme, which means that the GM1 ganglioside cannot be broken down. As a result, it accumulates to toxic levels in tissues and organs, particularly in the brain. This accumulation then leads to the destruction of nerve cells in the brain, which causes the features of the condition. How is it inherited? GM1 gangliosidosis is inherited in an autosomal recessive manner. Affected individuals inherit 2 mutated copies of the disease-causing gene, one from each parent. Carrier parents (with 1 normal copy and 1 mutated copy) typically are unaffected and do not have any signs or symptoms of the condition.

Likelihood of manifestation:
* When 2 carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% risk to not have the condition and not be a carrier. (it has equal sex distributions between male and female)
* It is important to note that GM1 gangliosidosis is type-specific within families. This means that individuals with a family history of the condition are generally only at increased risk for the specific type of GM1 gangliosidosis in the family.

How is it treated? There is currently no effective medical treatment for GM1 Gangliosidosis. Symptomatic treatment for some of the neurologic signs and symptoms is available, but does not significantly alter the progression of the condition.

* Patients with Gm1 gangliosidosis are at risk for aspiration pneumonia and recurrent respiratory infections resulting from neurologic compromise.
* Congestive heart failure may result secondary to cardiomyopathy (Cardiomyopathy is a weakening of the heart muscle or another problem with the heart muscle. It often occurs when the heart cannot pump as well as it should, or with other heart function problems. Most patients with cardiomyopathy have heart failure.)
* Atlantoaxial instability - Atlantoaxial instability (AAI) is characterized by excessive movement at the junction between the atlas (C1) and axis (C2) as a result of either a bony or ligamentous abnormality. Neurologic symptoms occur when the spinal cord is involved. AAI can develop because of abnormally shaped cervical vertebrae. (We know Eli has abnormally shaped vertebrae because of an MRI we have of his spine). If this occurs, patients should be monitored, and they eventually should undergo surgical stabilization to avoid the risk of spinal cord injury.

*Type I - Infantile - Type 1 will usually manifest within the first 6 months of life: Death usually occurs during the second year of life because of infection and cardiopulmonary failure.
* Type 2 - Late Infantile/Juvenile - The late infantile type usually manifests within the first 2-3 years of life, often around 18 months. The juvenile form will usually manifest after age 3 to 5. Type II progresses more slowly than type I, but still causes a shortened life expectancy. People with the late infantile form typically survive into mid-childhood (6-12 years old), while those with the juvenile form may live into early adulthood.
* Type 3 - Adult - Phenotypic variability is marked, but progressive development of neurologic sequelae usually leads to a shortened lifespan.

I reacted to this news by feeling sad, stressing out by searching the internet trying to find answers late at night, crying and over-analyzing. I couldn't think about much else for days. I was hoping and praying that Evan wouldn't have it, but told God that I would accept whatever happened. I didn't have to wait long for my answer.

My Mother's cousin's wife :) Lori Kunzelman is a radiologist and his been helping me tirelessly for the last month and a half trying to help me get this diagnosis for Eli. She helped me get in to see Dr. Aleck months earlier than what we were scheduled for. She told me about a Clinical trial for this disease going on at the University of Minnesota. They are doing Stem Cell Tranplants for children who could possibly benefit from them.  She encouraged me to email Dr. Aleck and see what he thought about it. I emailed him and instead of emailing me back, he kindly called me later that day to speak with me.

He told me that Dr. Narayanan, a Neurogenetecist in Phoenix who has been conducting a study for families and children with rare genetic disorders, had called him that day. Dr. Narayanan's office had all of our family's blood (we went and saw him back in February), except Laya's and was performing a full DNA genome sequencing study on them, and many other families. He had called Dr. Aleck to tell him that the DNA has proven that Eli and Evan both have the disease. Dr. Aleck told me he was sorry that he had to continually give me bad news over the phone. He encouraged me to look into the stem cell transplant so that we could get all the information we could and then make an educated decision about whether the possible outcome would be worth the risk or not. He proceeded to call Lori Kunzelman and tell her the news as well.

The following days I continued to feel depressed and exhausted emotionally and physically. I continued to tirelessly look up information and ask questions to people who were in a Gangliosidosis Facebook group. It was helpful to have a few long conversations with Brad, family and friends. It helped to write my feelings down and pray and accept. It was helpful to think of how I could make the most of this time I have with my boys and help others who may be in this same situation in the future. I feel now that I have accepted it and am ready to be happy again. I want to enjoy every moment. I know the road will be long, we will have heartbreak and sadness along the way, but we can also be happy. I hope that we will do all we can to stay close to each other and to God. 

Laya: Brad and I told Laya that Eli and Evan both have this disease. All we said was, "Evan has GM1 Gangliosidosis just like Eli and in the future he will become a lot more like Eli." She thought about it for a minute and then said, "Well maybe Evan won't be quite like Eli." We again reiterated the fact that Evan would indeed lose the skills and abilities he has. She then said, "Why do boys always have to have that kind of stuff?" (She was also thinking about another boy in school who has some intellectual disabilities). We explained it wasn't just a boy thing, but she quickly changed the subject and was back to her happy-go-lucky self again.
She doesn't know anything about the fact that her only two siblings will both most likely be gone from us before she reaches adulthood. We won't share that with her until it becomes very apparent and she is older and better equipped to handle these difficult things.

Here is a picture that was taken on Eli's 5th birthday, March 31, 2014.

He came home from preschool with this cute birthday crown taped to his helmet :)

The following pictures were taken very recently, but before the diagnosis. August 16 - Evan's 2nd birthday! 

 Enjoying his chocolate cake!

 Laya told us that we all had to wear our red reunion shirts for Evan's birthday, she set them all out for us the night before. Looking back at the matching pics, I'm glad she arranged our wardrobe for us. :)