Who knew that amongst the quiet farms of Lancaster County, major medical discoveries are happening?
A few weeks ago, we were all fascinated by an impeccably researched dive into health care in the “Plain” (Amish and Mennonite people) community by Sara Talpos in Mosaic Science. Given our location in Pennsylvania, it’s a topic of special interest to us. What really stood out was the information about the Clinic for Special Children in the nearby town of Strasburg.
The Clinic for Special Children was founded by Holmes Morton in order to help children of the Plain community with rare genetic disorders. Due to their religious beliefs, these people have chosen to isolate themselves from the rest of the world. This keeps the gene pool from expanding and leaves the community plagued by genetic mutations uncommon in the outside world.
Holmes Morton worked for Children’s Hospital of Pennsylvania when he encountered a four-year old boy suffering from brain damage. After the boy turned one, his health took a sudden turn for the worse. Morton learned there were other children in the community with the same symptoms. For years, doctors had assumed these sick children had “Amish Cerebral Palsy.”
Desperate to ease the child’s pain, Morton traveled to Lancaster to study the community and this disorder. Morton discovered the children were suffering from GA1, a metabolic disorder. GA1 prevents children from properly breaking down certain proteins. As they get older, they may experience seizures, become non-ambulatory and lose the ability to communicate. He worked directly with the community and was able to develop a formula to treat the children.
Since then, the clinic has discovered several other genetic disorders. It continues to grow and expand services to help these children and the larger community. While these disorders are rare, the Plain community isn’t the only one that is affected. Patients from abroad, including Iraq and Puerto Rico, have traveled to Lancaster to be treated.
With a budget of $2.8 million, no reimbursements and quickly advancing diseases, the Clinic must utilize resources wisely. Inspired by the Mosaic piece, I sought out and met with Adam Heaps, the Administrative Director of the Clinic, to discuss their methods of discovering and treating new illnesses.
How are you able to maintain a relationship with the community and receive so much support?
I think our [founding] story is what creates a strong relationship. We aren’t “medical tourists” here. A lot of people come, take some samples, do their research and leave without even telling the community what they have learned. We are rooted in the community here and are treating our patients.
How does your limited budget make you different from hospitals like CHOP? Is it difficult to work around?
Our budget this year consisted of $2.8 million. A third of that money comes from benefits. The Plain community will host benefit auctions where they sell quilts, mugs, etc. Proceeds are then donated to us. $2.8 million may seem like a lot, but it really isn’t when we are trying to accomplish what we are doing here.
Another portion of our budget comes from interested outside professionals. We work with these professionals to use their resources for answers when ours may not have the capabilities to do so. We also aren’t in competition with the local hospital. We can still easily send blood samples to them and receive the answers we need.
We don’t use model organisms or cellular studies for research, but we can partner with places like Franklin & Marshall who will use students and grants to get the research done.
How do your methods differ from a large hospital since you work with the Amish and Mennonite?
We have to consider time, money and media. These people don’t have health insurance, so costs need to be low. We actually don’t accept health insurance because of it. Commercial organizations can be expensive. We can do the same tests for $75 and offer results within an hour. Waiting for results from a commercial institute could take up to a week or longer. With severe life threatening disorders, it’s crucial to treat patients immediately. The faster we treat them, the healthier they will be. This will also lower the chance of future hospital visits. Often, when treating cases like this, patients have to be checked twice a week. Our families may not even have a method of transportation and a taxi costs a dollar per mile. By being placed directly in the community, we can check them easily.
We’ve integrated advanced scientific techniques and have an advanced lab. But we have to be selective with the type of media we use. When taking blood samples, we ask patients to use filter paper. They can then drop off the paper to us and we can review the results. The filter paper is great because they can do it as soon as they get up in the morning. The paper tracks circadian rhythms. If we had to wait for patients to come in during the afternoon to have blood drawn, we wouldn’t be able to accurately see how the treatment is affecting them. By afternoon, they’ve eaten and started their day.
We practice Translational Medicine. We take what we learn from our research and translate it into patient care. With GA1, we are able to diagnose a patient in 40 minutes and start providing treatment right away.
Before treating your patients, you have to first discover and research these diseases. Is there a certain process you use?
In the past two years, we standardized our methods. Now we abide by a four-step flow chart. The first step is to evaluate the patient and determine if the child’s problems are from a genetic disorder. If not, they will begin treatment right away. If it is, we will look into the targeted mutation. We know of 200 genetic mutations within the community. If it does not match one of them, then we will do a cytoscan using microarrays. If we still can’t identify the disorder based on that, then we will use Exome Sequencing. All DNA is comprised of 3.5 billion base pairs. We receive one from our father and one from our mother, giving us 7 billion base pairs. Exome Sequencing allows us to review the 1% that encodes protein. This will signify which genes aren’t properly breaking down an enzyme. We want to add a fifth step to the process—whole genome sequencing.
Since we have been able to partner with outside organizations, we have found 32 new mutations of current disorders. That’s triple the amount we found last year. New could mean a new discovery or new to the Plain folk.
One of our greatest tools is using natural history studies and examining the current patient's family tree. Natural history studies look at the normal course of the disease. This gives us a baseline for being able to measure if treatment options have positively changed the “normal” outcome or not. Being able to communicate with and study a person’s siblings and cousins gives us great insight as to what DNA trait is causing issues.
After discovering a new disorder, how do you develop your treatments?
We conduct clinical trials. We will take a decent number of patients with the same mutation, then conduct interval trials. For example, when we began testing treatment for CAH, we used existing drugs on the market and studied how taking them at different times would affect that person.
We monitor the results based on the family’s report. This could be biased; everyone wants to believe their child is getting better. So we give them a chart to fill out. Are they getting more or less irritable? How effectively are they able to communicate based on this scale? Those types of questions. There is also, of course, the biochemical component of the treatment which is monitored closely.
Are there dangers in treating patients with existing drugs or diets?
Yes. When changing a patient’s diet to treat GA-1 and MSUD, you are removing a protein their body can’t break down. However, there is still a certain amount of amino acids needed to properly function. For example, when we tested CAH, patients used the two drugs on the market. One was short-acting and the other was long-acting. We asked patients to take the longer-acting drug in the evening. This pill protects against low glucose levels. A patient could go into a coma while asleep if their glucose levels get too low. For most people, these risks are worth the trials.
When GA1 was first discovered, 95% of patients died. They had suffered extreme brain damage. They would be victims of seizures and would never be able to communicate with loved ones again. Parents feel the reward is greater than the risk. And it is. Now, 0% of patients will die from GA1. The community understands these children have a very dim future. These disorders are so devastating. Trying anything is better.
Of course, we do take precautions. By studying the natural history we are able to predict how the drugs will affect that person. Studying the natural history, the clinical studies and forming effective treatments allows us to predict that person’s future. We can tell them exactly what they are going to face as they get older while helping to diminish the symptoms.
You spoke of having to always consider time, media, and money when treating your patients. Have you had to think out of the box when studying genes because of this?
Working directly with the community is what makes us unique. We have had midwives bring us cord blood in order to do research. By using this method, we have stayed true to the family's religious beliefs by not testing the fetus and can tell within 24 hours of birth if the child will need treatment.
Some of the more innovative things we have done is trying to treat all the symptoms accompanied with the disorders. We want this place to be a medical home for them. We have many different subspecialists who come to treat the patients. Our ortho surgeon even comes all the way from Akron, Ohio.
Hearing loss is often a primary or secondary symptom to these disorders. It can happen to the child as early as six months. Using the cord blood, and reviewing the natural history, we can predict if children will become deaf. The good news is that we now know they respond well to cochlear implants. We have audiologists come and help these children. We even have our own testing booth in the basement next to our lab.
We also teach parents how to deal with these complications. Many of these children have extreme mental health needs. 60-80% of disorders come with neurological issues. These children have seizures and can be developmentally delayed. We offer behavior therapy and try to give parents tools on how to care for their children and what to expect. Family days are held to address families with children suffering from the same disorder. These are huge social and educational events. They really help these families cope with the news.
How has your research impacted the larger community?
We have contributed to the basic science. We’ve provided a lens into how things work. We provide an insight into what happens in a person when you turn off a gene. This is what attracts so many professionals to helping us. Our research and the way we work with the patients makes them think about what it is they are doing.
These disorders aren’t exclusive to our community. We have had patients come from abroad. From the Caribbean to the Middle East, they do exist elsewhere.
The research that has been the most impactful is probably the paper we wrote on CASPR 2, a neurexin-related cell-adhesion molecule related to autism. It is essentially a genetic disorder which causes children to feel no fear. This spurred research into the genetics of autism. Kids with CASPR 2 will jump out of windows and run in front of a train because they don’t understand they should be afraid of it. Families can have as many as five children who suffer from this! We’ve researched the natural history, but we still don’t understand it. Some aren’t ambulatory who suffer from it. Others can walk. We try to equip parents with strategies, but there is much we don’t know yet.
What do you think the future is for this Clinic and research?
Adult care. The demographics of the Amish and Mennonite population is growing quickly. They stay in the Old Order church and the number of children are increasing without introducing new genes. Our biggest challenge will be to develop a strategy to think ahead. How do we help these children once they become adults? 31% of our patients are now 14 and up. We are all pediatricians. We aren’t trained to treat adult situations and we are running out of space. We will need to think about what the next move will be to accommodate them.