A DARK INHERITANCE

By THOMAS ULRICH

It is fall in Pennsylvania's Lancaster County, and Jacob Stoltzfoos is working his field much the way his forebears did three centuries ago--tugging at the yoke of a Belgian draft mule. The only sounds he hears are the snap of a rein across the mule's hindquarters, the simple mechanical whirl of his corn-harvesting machine and the creak of his oak-plank wagon as he hauls another stack of feed corn to his son-in-law's silo. Like their ancestors, Jacob and his kin light their farmhouses with gas lanterns and drive carriage horses--never automobiles--back and forth to town.

Jacob and his family are Old Order Amish. They belong to a community that lives at the edge of American society, with spiritual values rooted in Pennsylvania-Deutsch soil. Most of the 20,000 Old Order Amish living in Lancaster County are descended from the 200 German-Swiss farmers who immigrated there during the 18th century. The community has paid a price for its separateness: because the Amish forbid marriage outside the Old Order, centuries of inbreeding have afflicted them with certain genetic diseases that strike their young in alarming numbers.

"Twelve disorders that I see here are founder-gene defects carried by the dozen families that established this population 300 years ago," observes Dr. D. Holmes Morton, 47, a pediatrician and geneticist who gave up an academic career to work among the Amish. One of those diseases, he has discovered, is glutaric aciduria, a metabolic deficiency that usually strikes children between the ages of 6 months and 5 years. Often triggered by childhood illnesses such as chickenpox or strep throat, it can cause permanent brain injury that can lead to chronic disability, medical complications and even early death.

Morton's introduction to glutaric aciduria and the Amish came one night in 1987 while he was on duty in the clinical laboratory at Children's Hospital of Philadelphia. A fellow physician, Dr. Charles Nichter, asked him to analyze the urine sample of an Amish child, Danny Lapp, from Lancaster County. At the time, Danny was alert but had no control over his arms or legs--signs of cerebral palsy, which was Nichter's medical specialty. Morton's testing revealed a metabolic fingerprint that could be caused only by glutaric aciduria, a disorder that had previously been reported only eight times worldwide--and not once in Lancaster County.

In fact, it was not the first case, nor would it be the last, from Amish country. Curious about the nature and cause of Danny's cerebral palsy, Morton decided to visit him at the Lapps' home near Leola, Pa. Danny, who was six at the time, sat strapped to a wheelchair, his legs flailing, while his parents, John and Ida, told Morton about many Amish parents who had endured similar heartbreaks. Five years after Morton's first visit, Danny Lapp died of the disease.

"What began as a personal challenge quickly became a personal responsibility," recalls Morton, a West Virginia native who worked the Great Lakes iron-ore and coal boats and served in the Navy before studying biology and psychology at Connecticut's Trinity College and getting his M.D. at Harvard. "I knew from the start I could treat these disorders, and I soon felt a great responsibility to these children without knowing how I could possibly care for them."

Recognizing that the Old Order Amish and Mennonites (who suffer from a similar genetic disorder called maple syrup urine disease) could not reach major medical centers if their children became ill--particularly since the condition often deteriorates in a matter of hours--Morton and his wife Caroline decided to build a clinic in Lancaster County. Lacking government, university or foundation support, they applied for a second mortgage on their home in St. Davids, Pa., to raise money for lab equipment. Their chief need was for a mass spectrometer that, together with a gas chromatograph and a computer workstation, would provide the technical means to diagnose and record cases. Having read about Morton's work in the Wall Street Journal, Hewlett-Packard co-founder David Packard donated all three machines, and within three months the Mortons were screening Amish newborns.

Grateful that Morton had diagnosed a granddaughter's illness during his early visits to Lancaster County, Jacob and Naomi Stoltzfoos sold the Mortons, at half market value, 2 1/2 acres of land as a site for the clinic. Two Mennonite congregations contributed a liquid chromatograph for analyzing blood samples of children who might suffer from maple syrup urine disease.

One blustery November afternoon in 1990, 12 Amish carpenters and 55 Amish and Mennonite farmers raised the Clinic for Special Children. Wielding sledgehammers, Douglas fir timbers and stout oak pegs, they framed the post-and-beam building by the end of the day. "Now when Jake's mules turn at the end of a row," says Morton, "he often looks to see if I am at my laboratory window. He has grandchildren with the disease I'm studying, and we both hope they can live to work in the field."

"When Dr. Morton told us that our daughter Barbie Ann had glutaric aciduria, John and I thought he had made a mistake," says Lydia Stoltzfoos, daughter-in-law of Jacob and Naomi. But Barbie Ann soon developed a fever, and Morton admitted her to Lancaster General. Stressed by infection, a child with glutaric aciduria does not metabolize certain amino acids normally. The resulting buildup of glutarate attacks the nervous system and damages the basal ganglia, a part of the brain that controls body movement. Once brain injury occurs, a child never recovers. "If it weren't for Dr. Morton and the clinic," Lydia says, "Barbie Ann would have ended up like many of Amos and Suzie Miller's children. Five of them died or are paralyzed because of this disease."

Over the years, Morton has traced each family's genetic heritage through 14 generations. He has determined a carrier frequency for the disorder among the Amish of about 1 in 10 people. Working with Dr. Richard Kelley, a pediatrician, Morton diagnosed glutaric aciduria in 16 other Amish children. The doctors' studies predicted that 50 more children born in the next generation would inherit the two copies of the defective gene needed to cause the disorder. According to the statistics, without treatment nearly all would be disabled, and 12 of them would die before age 5. "Glutaric aciduria is a treatable disease, so we need to know who is at risk during the first few days of life," says Morton.

Discovering early just who has glutaric aciduria is more than half the battle. Once the disease is diagnosed, Morton's main task is to put his young patients on a low-protein, high-riboflavin diet to lessen the effects of the disorder and prevent medical complications. If a stricken child can survive to age 5 with this help, he or she typically becomes resistant to the worst of the disease.

Meanwhile, Morton's clinic has become a model for rural health care, reducing hospitalization for the disorders to one-tenth their historic rates. The Amish and Mennonites who use the clinic do not buy medical insurance or subscribe to Medicare, but instead depend on family and community for help. Says Dr. C. Everett Koop, former U.S. Surgeon General: "Holmes Morton has forced his way into the hearts of the Amish people and, based on that trust, has accomplished a remarkable service."

Morton may well have performed an even more remarkable service to modern medicine by establishing a link between metabolic disorders like glutaric aciduria and cerebral palsy. Most practitioners have long believed that oxygen deprivation or trauma at or before birth causes cerebral palsy, a motor disorder that reflects injury to the cerebral cortex and basal ganglia. But Dr. Karin Nelson at the National Institutes of Health, as well as colleagues at other research centers, has concluded that these causes do not explain most cases of the disease. "Holmes Morton has given us fresh insight into the source of cerebral palsy," says Nelson. Adds Dr. Victor McKusick, professor of medical genetics at Johns Hopkins University: "The beauty of his research is that we can apply it to children all over the world."

Morton and his colleagues have tested thousands of Pennsylvania newborns for inherited metabolic disorders during the past five years and in the process discovered that more than half the children with glutaric aciduria are not of Amish descent. In fact, Morton points out, many countries, including Ireland, Germany, Sweden, Israel, Spain, Saudi Arabia, Canada and the U.S., have clusters of children with glutaric aciduria.

When he received the Albert Schweitzer Prize for Humanitarianism in 1993, Morton noted how his practice--and his life--had changed since he arrived in Lancaster County. "At first I shared information with this community that I thought would help them. Now I am indebted to them for what they have shared with me. As outsiders, we tend to view Amish traditions as archaic and feel they don't have much to teach us. But we should look at how the Amish keep families together and serve the needs of the disadvantaged, the ill and the aged. They have a much better way of dealing with these problems than we have."

Morton recalls visiting an Amish family just before he established his clinic. "We will be glad if you can learn to help these children," said the father of a boy who had just died. "But such children will always be with us. They teach a family how to love and accept the help of others." Morton has not only helped one small community on the fringes of modern society but also taught the world something new and quite important in the process.