As the gastroenterologist wrote up orders for bloodwork for my infant son, whose liver function was out of the normal range, she said, “Don’t worry too much. If he has one of these disorders, it would be like getting struck by lightning twice.”
In about a week, we got the lightning-strike results: My son not only has cystic fibrosis but also another rare genetic disorder — alpha-1-antitrypsin deficiency, or Alpha-1. That means his father and I are both carriers of the Alpha-1 mutation. While many have probably never heard of the disorder, it’s estimated that some 23 million people in the U.S. are carriers, and an estimated 100,000 people have Alpha-1 itself, meaning they have two copies of the mutated gene that causes the disorder.
People with two mutated genes have low levels of the alpha-1-antitrypsin (AAT) protein, which is made in the liver and protects the lungs from inhaled irritants like tobacco smoke and damage caused by inflammation. The mutations result in a protein that is misfolded and can’t leave the liver to circulate in the bloodstream. Thus, abnormal protein builds up in the liver, which can cause liver disease.
People with Alpha-1 can also accumulate lung damage from smoke or other inhaled toxins over time. Many develop COPD as adults, even in the absence of a smoking history.
As we met with pulmonologists and gastroenterologists, we learned that, unlike cystic fibrosis, even carriers of Alpha-1 have a slightly increased risk of health problems related to the deficiency. Still, most people with either one or two Alpha-1 genetic mutations are walking around with no symptoms at all, nor any clue that they have the potential to get emphysema or cirrhosis of the liver, even if they never smoked or drank to excess.
As we met with pulmonologists and gastroenterologists, we learned that, unlike cystic fibrosis, even carriers of Alpha-1 have a slightly increased risk of health problems related to the deficiency.
Most pulmonologists associate Alpha-1 with very sick patients who have severe deficiencies in an advanced stage, so they may miss patients in early stages who are just starting to have lung damage and whose symptoms may be nonspecific, like asthma or recurrent lung infections.
The only specific treatment for Alpha-1 right now is an infusion of the AAT protein from the plasma of healthy human donors. This weekly intravenous infusion must be continued indefinitely and can cost $150,000 per year or more. Most people on the therapy have already sustained long-term lung damage.
But what if people knew their status and could start treatment before the damage began? What if parents knew their children’s status and could make lifestyle modifications that could reduce their chances of lung damage, like avoiding second-hand smoke exposure, staying indoors during ozone alerts, and avoiding occupations that would expose them to particulate matter, such as firefighting or construction work? We wanted to know, so we got our other child tested for Alpha-1 as well.
A few years ago, I purchased the 23andMe test for my children and me. At that time, the direct-to-consumer genetic testing company wasn’t offering health reports, only ancestry data. But when I logged in a few months ago, I learned that the company had relaunched its health reports, including one for Alpha-1. Immediately I thought of all the carriers and people with Alpha-1 itself who would be finding out about their genetic status. What would they think? Would they get the information they needed to follow up with their physician? Would they take it seriously? Would they be grateful they’d learned about their risk, or would fear of the disease rule their lives?
Curious, I asked Terence Flotte, our son’s pulmonologist at the University of Massachusetts Medical School, what he would tell someone who’d found out via 23andMe that they have Alpha-1.
“Anyone who has an abnormal finding, even carrier status, should ideally be seen at an Alpha-1 clinical center,” he told me. “That’s my personal advice, and it may be more prescriptive than some. But I think we should be careful calling [people who have one gene mutation that lowers alpha-1] ‘carriers’ — they’re technically carriers, but their risk for COPD is two to two-and-a-half times greater with environmental exposures. They should get more information and speak to a professional [about] their own health, lifestyle issues, and genetic counseling for future generations. While the primary interventions we have right now are lifestyle ones, they are critical lifestyle choices that I think people make differently when they know they have [or carry] Alpha-1.”
He also says that sometimes the data can be confusing, so additional testing through an Alpha-1 center can help pin down the diagnosis. And sometimes the Alpha-1 center can collaborate with the person’s primary care physician to do extended testing.
Right now there are roughly 10,000 people in the U.S. who have been diagnosed with Alpha-1, and an estimated 100,000 to as many as 500,000 people who are carrying two variant genes that cause a severe deficiency. These numbers mean that more and more people are going to find out via direct-to-consumer testing that they have Alpha-1 or carry one mutation for it.
I spoke with Kristin Platt, a 42-year-old woman who lives in Houston. She had purchased a 23andMe test primarily to research her ancestry, but also because she had a family history of Alzheimer’s disease. While she was relieved when she found out she didn’t carry the mutation that puts her at higher risk of developing Alzheimer’s, she did learn that she has severe Alpha-1.
“At first I thought that if I haven’t heard of it, then it must not be that bad,” she says. “Then, when I read on the 23andMe website that most people with two variants develop emphysema, that stopped me dead in my tracks.” Platt had just finished several rounds of antibiotics and steroids for bronchitis that wouldn’t go away and had been diagnosed several years earlier with adult-onset asthma (which Flotte says is a fairly common diagnosis for alphas).
Platt saw a pulmonologist, who confirmed the diagnosis and told her it was good they’d caught it in the early stages. Usually, the earlier the treatment begins, the better the outcome. She decided to start AAT protein augmentation therapy right away.
“That was a big decision,” she says. “I went from having a lingering cough from bronchitis to getting an IV once a week for the rest of my life.” But, she says, she feels good about her choice and is reassured to know that she’s doing all she can to prevent further damage. “When I first found out, I was in a really dark place. I had to face that fear that, dear God, this could kill me, and more than likely, this is what’s going to kill me someday. I had to do some deep searching and I finally came to the conclusion that this diagnosis was a great gift.”