Solving riddles of genetics
For nearly 30 years, a Lancaster County clinic has specialized in diseases affecting Amish and Mennonite children, writes Art Petrosemolo
When the first Amish and Mennonite families reached Pennsylvania in the 1700s, they brought along genetic mutations that, when passed to their children, could result in infant death or lifelong debilitating conditions.
The pain and suffering felt by this culturally bound group is much diminished these days. Their children now can lead normal lives thanks to groundbreaking treatments by the Clinic for Special Children in Strasburg, Lancaster County, working with regional medical partners including Children’s Hospital of Pittsburgh of UPMC.
These rare genetic disorders are observed even today (12 generations later) in Amish and Mennonites. One disease — GA1 (Glutaric Acidemia Type 1) — originally was identified in the 1950s but at the time not connected with the Amish. Another disease — MSUD (Maple Syrup Urine Disease) — is observed in the Mennonite community. Both diseases affect the body’s ability to process amimo acids, which are the building blocks of protein. Without treatment, high amino acid levels can cause brain damage. Children with GA1 face severe physical disabilities while those with MSUD can suffer both physical and intellectual problems. Children affected with either disease require the use of wheelchairs.
There are no obvious early physical manifestations of these diseases, and they can be detected only by biochemical or genetic testing. Children who unknowingly had these disorders would seem healthy and then suddenly become disabled or die with little warning. With little understanding of the cause or substantive help from the medical community, so-called plain families long prayed for help and a better sense of what was happening to their offspring.
• The development of treatments is a story worth knowing. It dates to 1989, when a physician on a biochemical fellowship at the University of Pennsylvania, Holmes Morton, diagnosed and worked to treat a case of GA1 in a Lancaster County Amish child. He then identified and treated 16 additional cases in Lancaster Amish families. His discovery connected for the first time GA1 with the plain communities. With his wife, Caroline, and partnering with both Amish and Mennonites, Dr. Morton started the nonprofit Clinic for Special Children in 1989 with a strategy to integrate scientific tools and concepts in clinical practice to aggressively treat these two genetic diseases and other genetic-related diseases.
MSUD and GA1 are recessive disorders. When both parents are carriers of the genetic mutation, they have a 25 percent chance of having an affected child. In large plain community families, one or more children could be affected.
If Amish children with GA1 can reach age 3 without brain damage, then their risk of developing it in later years is very low. However, that is not the case with Mennonite children with MSUD, for whom the most effective long-term treatment is a liver transplant.
What the Clinic for Special Children has done in the past 28 years has been life altering for countless families. Before the opening of the clinic, now led by medical director Kevin Strauss, outcomes for plain community children who had GA1 or MSUD were devastating. Children had a nearly 95 percent chance of debilitation or early death. Today, because of new treatments and liver transplants, children with the same diseases have a 97 percent chance of leading normal lives.
When clinic physicians began their work in the 1990s, the most effective treatment for GA1 and MSUD was a strict low-protein diet to keep the amino acid levels within a range where the brain was not affected.
For more than a decade, researchers at the clinic and elsewhere worked on formulas to help control this buildup of amino acids. “At the time, none of the medical foods on the market had been evaluated through a clinical trial,” said Adam Heaps, the clinic’s current executive director. “In 2006, CSC researchers developed GlutarAde and Complex Essential, based on research related to how amino acids get from the blood to the brain, which helped revolutionize treatment of both GA1 and MSUD patients.”
To this day, the development of the medical foods has helped the clinic physicians keep both diseases under control. In cases of GA1, that is until the children reach age 3. In cases of MSUD, that is until the children receive liver transplants. Both products are powders similar to a baby formula. They are mixed with water and consumed by patients in a prescribed plan at a reasonable cost.
The clinic has been an early proponent — with the support of the wider medical community and area midwives — of blood screening for infants to see whether they have a disease-carrying gene so treatments can begin immediately.
For nearly 15 years, CSC has partnered with Children’s Hospital of Pittsburgh and worked closely with George Mazariegos, chief of pediatric transplantation, to provide liver transplants for Mennonite children with MSUD and other metabolic diseases. To date, more than 100 CSC patients with MSUD have received successful liver transplants at the hospital.
Children’s has a long, successful history of organ transplants and was one of the few hospitals to perform liver transplants for children with metabolic disorders, explained surgeon Kyle Soltys. Hospital doctors visit the CSC frequently and run an annual transplant clinic for pre- and post-transplant examinations and tests so the children and their parents don’t have to make the 400-mile trip to the hospital and back. “Our relationship has matured over the years,” Dr. Soltys said. “It’s a winwin scenario for both the clinic and the hospital. The doctors and staff at the clinic are part of the team caring for these transplant patients, rather than just being referring physicians. We work together closely and provide team care for these children.”
Besides treating genetic diseases, the Clinic for Special Children serves as a primary care facility for the plain community with a staff that understands the culture and its special needs. The clinic has 1,100 patients who made 1,600 patient visits in 2016. Some 4,000 genetic and biochemical patient tests also were conducted during the year.
Janelle Hurst has been a clinic patient for 27 years. She has a disorder similar to cerebral palsy, and her parents, Leonard and Laura, rave about Janelle’s care. “Clinic doctors and staff treat you like family,” Mr. Hurst said, “and are willing to take the time 24/7 to answer your questions regarding care and treatment.” Mr. Hurst has served on the Clinic board since 1996 and helps with fundraising.
CSC is wedded to the community. The facility was built off the beaten path in Lancaster County, on land that was owned by an Amish farmer whose granddaughter was one of the clinic’s first patients. The building, of solid Amish post and beam construction, was raised in 1990. It houses examination rooms, labs for genetic testing and research, and meeting and office space for the 16 doctors, plus researchers and support staff, including a molecular geneticist.
Mr. Heaps joined the CSC as a lab technician in 2010. He served as a lab scientist as well as CSC’s administrative director before being named to his current post in 2016. Founder Morton helped open and now is working at a similar clinic for the treatment of the plain community near Belleville, Mifflin County.
To expand its reach, the CSC opened a branch facility in Salisbury, Somerset County, in 2012 to serve a small Amish population that had limited access to quality health care and difficulty making the trip to Strasburg. Dr. Strauss and a nurse make the nearly 400mile round trip several times a year to see patients.
Dr. Strauss said the genetic makeup of the Salisbury area community is more closely aligned to the Amish families in Ohio than Lancaster County. One of the diseases being treated there is an enzyme deficiency (GM3 synthase deficiency) first discovered in the Ohio Amish and not often seen in the Lancaster County community. The CSC is working with its Children’s Hospital partner on new treatment options for the disease.
Funding for the CSC is primarily through gifts, with 60 percent of the $3 million budget raised yearly through donations and fundraising events, including large benefit auctions. Patients are charged $50 for office visits and comprehensive testing. It is estimated the clinic saves the communities it serves more than $20 million yearly in medical expenses with infant testing, early diagnosis and treatment of genetic diseases and reduced hospital stays.
CSC maintains a comprehensive ongoing education program for the plain communities and the health care professionals who serve them. And the clinic continues its research and partnership with institutions like Children’s Hospital on genetic disorders that affect plain communities, which continue to grow in Pennsylvania and in enclaves in several other states.