Bigfork resident working to get screenings in Montana for rare deadly genetic disease

Bigfork resident Steve Shapero remembers when his brother was diagnosed with X-ALD in the 1980s — a genetic disease that later led to loss in his mobility.

At the time, it was considered improbable to be a carrier if you had no symptoms. Shapero would later find out that’s not true.

“I knew my brother had inherited it from our mom and that each of us had a 50-50 chance of getting it,” Shapero said. “Since I had no symptoms they didn't check me when my brother was diagnosed, so I unknowingly passed it to my daughter, who then unknowingly passed it to my now 9-year-old grandson.”

In the fall of 2020, Shapero was surprised to learn he had inherited X-ALD.

Now, Shapero is working to get the disease that’s full name is X-linked Adrenoleukodystrophy as part of screenings that occur at birth through the Montana Department for Public Health and Human Services. Currently, Montana is one of 21 states that doesn’t test for X-ALD as part of its newborn screening panel. The United States Department of Health and Human Services includes X-ALD as one of 35 rare diseases in their ‘Recommended Uniform Screening Panel.’ Last year, the Montana State Legislature passed a law that would call for the creation of an advisory committee for the state’s Newborn Screening Panel. This created an avenue for citizens to voice their concerns and rally for certain diseases to be added to the list of mandatory screenings.

Shapero created the Bigfork Independent Film Festival but recently announced he is taking a step back to focus on solidifying X-ALD on the state’s screening panel through this new process.

“Hopefully by the end of this year or next year they'll be able to consider it. You have to provide a lot of information on the metrics of the disease, how frequently it pops up and how they can test for it. But, I've been talking to them about this since early 2021, just before the bill went through, because I wanted to get on their brainwaves. I want them to be aware that I'm pushing for this,” Shapero said.

With symptoms similar to other neurological diseases like multiple sclerosis, X-ALD is caused by a mutation of the ABCD1 gene found on the X chromosome. Because it is linked to the X chromosome, severe symptoms are much more common in males than in females. There are four different X-ALD phenotypes that come with different symptoms: Asymptomatic, Adrenal Insufficiency, Cerebral ALD and Adrenomyeloneuropathy.

Adrenal Insufficiency can destroy the body’s adrenal glands where they can no longer produce the steroids cortisol and aldosterone. While usually nonfatal, an untreated acute adrenal crisis can become a dangerous medical situation. Adrenomyeloneuropathy is the most common and impacts males around the age of 30. It’s caused by demyelination of the nerve tracks in the spinal cord which impacts the lower extremities and leads to impaired balance and loss of use in the legs. Cerebral ALD, or CALD, is the most deadly, primarily impacting boys between the ages of 4 and 10. The disease creates an inflammatory response in the white matter of the brain which leads to lesions and nerve cell death. CALD is highly progressive and if left untreated results in a vegetative state or death within a few years. If diagnosed early, it can be treated with stem cell transplant. New gene therapy also shows promise for boys that don’t have a matched sibling or an available and willing unrelated Human Leukocyte Antigen, or HLA matched donor.

Shapero said his grandson James must go get a brain scan every six months to ensure he hasn’t developed CALD.

“We had a scare last December with my grandson because his doctor found a couple spots on one of his MRIs. He lives in Oklahoma and we had to fly him back out to California three months later to be tested. Fortunately, it went away, they don't know what happened to those spots but they're not there anymore. So, it's something you really have to watch carefully,” Shapero said.

While it is primarily a hereditary disease, 20% of X-ALD cases spontaneously occur — meaning it can show up in a gene pool and unknowingly get passed down. Particularly with CALD, time is of the essence when it comes to diagnosis and treatment.

The response, if something is found, is extensive so it’s important to catch anything as early as possible, he notes.

“If they do see something they don't like, they have to find a bone marrow match, and if they don't have a full-blooded sibling that can be really hard to do,” he said. “ It can take many months. You have to find someone willing to donate their bone marrow.”

Although severe symptoms are more rare in women, Shapero’s daughter also suffers from X-ALD in its adrenal insufficiency phenotype. She has to take medication three times a day for her adrenal glands, much like her uncle who has AI as well as Adrenomyeloneuropathy, which has slowly taken away his mobility.

For reasons he and his doctors don’t understand, Shapero hasn’t developed any symptoms.

“I'm kind of a true oddball, an outlier for this disease, because there's only a handful of us known to exist. For some reason we have a sort of protective mechanism in our bodies that keeps all this damage from happening,” Shapero said.

The toll the disease has taken on his family has been a rollercoaster of emotions. From feeling sympathy for his brother, to relief that he doesn’t have it, to the news that he does have it and has unknowingly passed it down to his children and grandchildren. The experience has driven Shapero to focus on preventative measures to ensure other families don’t have to be left in the dark.

“This thing can happen spontaneously, like it did in our family. We don't have a long line of relatives or ancestors that had this, it just happened to my mom. If you're not aware of it, you don't know it exists and you can think of something else.”

“If you wait too long, before diagnosing it, then it's too late,” he adds. “You can't really do anything and the child will die. So that's the main reason why I think we need to be testing babies in Montana, because if we can catch it early enough, then they can keep an eye on it, then it almost guarantees that they're going to survive.”

Anyone interested in learning more about X-ALD can find support and information through ALD Connect on Youtube and the ALD Alliance. Shapero said anyone who wants to aid in his effort to get the disease added to the Newborn Screening Panel in Montana can reach out to the state’s Department for Public Health and Human Services.