What killed 2 ½-year-old Mary Smith?
Dr. Heng Wang mulled over a theory as he drove along Route 528 in Middlefield, about 45 miles east of Cleveland. That September day, he paid little attention to the changing autumn colors or the picture-postcard rural setting, with turquoise and sea-green dresses and white bonnets drying on clotheslines at the Amish farms he passed.
He focused only on finding the long gravel driveway leading past one farmhouse to the Smith home. He knew the Smiths weren't expecting him.
The Smiths (who asked that their real name not be used) are Amish, so they live a quiet, conservative life with no phone, no electricity and only a horse-drawn buggy for transportation. Wang had written them a letter saying he might know what now afflicted another of their children, Jacob. But he had no way of knowing if they had received the letter and even if they had, because the Amish are cautious about opening up to outsiders, he didn't know if the family would welcome him.
Wang's quest that fall day was to get a urine sample from 3-year-old Jacob.
Even in a town as rich in medical science and world-renowned specialists as Cleveland, numerous doctors couldn't tell Elizabeth Smith why Jacob had so many infections he couldn't easily fight off. Or why exactly his sister Mary died. They knew that when Mary died, her tiny body was ravaged by a staph infection and her heart failed from a condition called cardiomyopathy.
But the doctors could never answer the question: Why?
Wang, a general pediatrician, estimates he has made about 100 house calls to Amish farms since he started working in Middlefield in May 2002. He's medical director of a new nonprofit clinic, called Das Deutsch Center for Special Needs Children, that cares for children with metabolic and genetic disorders, many of which affect the Amish. The Amish represent just 12 percent of Geauga County's population, but account for 45 percent of the children with mental retardation and other special needs. Das Deutsch Center will also serve non-Amish children and children from other counties.
When the center's modern clinic opens in March, Wang will cut back on the house calls. But for now, he goes from home to home, spending hours with each child and family.
The visit that sticks in his mind most is the day he first met the Smiths.
Wang found their long, unpaved driveway and drove slowly by one farmhouse, past piles of freshly chopped firewood stacked for winter, to the Smith home.
The family welcomed him, saying they had planned to find a phone to call him that day. Elizabeth told him that the similarities between Mary's condition and Jacob's haunted her, and that she knows in her heart that Jacob has the same disease that took her daughter's life. So she has allowed doctors to treat Jacob's infections, but won't let him suffer through numerous tests and costly hospital stays as Mary did. Like many Amish families, the Smiths do not have medical insurance.
When Wang told them he needed a urine sample from Jacob, they said he'd just gone to the bathroom, so they suggested Dr. Wang return another day. He agreed, but as he started to leave, he stopped to ask just one more question. "Where did Jacob go to the bathroom?"
And there it was: a perfect urine sample still sitting untouched in the bowl of a child's plastic potty chair. Wang poured it into a cup and left.
That sample was the key to solving a mystery in the Amish community. In just four months on the job, Wang discovered a rare disease among the Amish: proli-dase deficiency, an enzyme disorder that causes painful skin ulcers and recurrent infections throughout the body. There is no known cure.
Wang proved that this disease, reported in fewer than 40 people worldwide since its discovery in 1968, afflicted both Jacob Smith and an unrelated 8-month-old Amish boy who lives a few miles away, near Middlefield. Most likely, the same disease kept little Mary Smith from fighting off the infection that killed her.
"We didn't expect a major medical breakthrough for four or five years," says JoAnn Leach, a Das Deutsch Center founding board member. "He has amazed us all."
“Amazing" is a word often associated with Dr. Heng Wang, although it's one that he shyly shrugs off.
At 20, Wang became one of the youngest doctors in China when he graduated from Anhui Medical College in the top 3 percent of his class.
His parents were teachers, so, as a preschooler, he sat patiently in the back of his mother's class each day, learning enough to start school early.
After med school, he went into research, earned a master's at a school in Beijing and received his Ph.D. from the University of Liege in Belgium in less time than anyone before him. He wrote his thesis in English, but presented oral arguments in French.
He's held two research fellowships and a postdoctoral fellowship at Baylor College of Medicine in Houston, and he's published more than 30 scientific papers, mostly on nutrition issues in newborns, in reputable medical journals including the American Journal of Physiology and Pediatrics Research.
But after years as a researcher, Wang shocked his colleagues at Arkansas Children's Hospital by asking to do a pediatric residency at age 36.
After his residency, he had numerous offers. Baylor College of Medicine wanted him back. Arkansas Children's Hospital wanted him to stay. He was already working as a general pediatrician in a clinic, seeing up to 30 runny noses and ear infections a day.
Wang's wife Jianhui (called Jan) admits she urged him to return to Houston. They had good friends there. The Baylor position would've been a prosperous and comfortable job.
But something fascinated him about the ad in the Journal of Pediatrics for the job at Das Deutsch Center. There, he could work with children and do groundbreaking genetics research — the best of both worlds. The job would be, in his words, "a blank paper you can draw a beautiful picture on."
He came to Middlefield in December 2001 to meet with Das Deutsch board , members. About half the board members are Amish men who have children with special needs. Wang visited with some of the families on their farms.
His last stop was the home of Daniel and Katheryn Miller of Middlefield. Four of the eight living Miller children are severely handicapped; a fifth handicapped child died. The children are in wheelchairs, with three of the four on feeding tubes. Seven-year-old Owen is so frail that he can't go to school anymore. He lies in a bed visible from the living room, periodically thrashing and crying out. The children have never received a diagnosis, but seem to suffer from the same syndrome.
Wang had an hour and a half to make his flight — the airport is about 50 miles away — and it was snowing.
"He picked up Matthew and held him," recalls JoAnn Leach, who accompanied Wang that day. "I offered him coffee, but he said no, he just wanted to hold Matthew for a while."
Wang trudges through freshly fallen snow to the back door of what appears to be a farmhouse. He walks in through an enclosed porch to a large room warmed by a wood-burning stove. Nine Amish women are singing "The Wheels on the Buggy Go Round and Round" with a large group of children. The little girls wear black bonnets, the boys wear mostly bright-colored shirts with black pants and suspenders. It is the day before Thanksgiving and construction-paper turkeys adorn the walls. A sign made from red paper reads, "Welcome To Sunny Hope." This is Wang's first visit to the school he's heard so much about. Sunny Hope is strictly for Amish children with special needs. The school is renting this house for a year and hopes to build its own structure by next year.
Looking around the room, he recognizes only a few of the 29 youngsters, who range in age from 4 to 20.
Two of his patients who attend Sunny Hope are Joseph, 4, and Leanna, 7, who recognize Dr. Wang and smile. They are the children of Bob and Mary Lou Miller. Joseph, the youngest in the school, is a small boy with a traditional Amish bowl haircut that frames a cherubic face. His walk is wobbly because he suffers from cerebral palsy and may have other developmental delays. Leanna, a quiet, sweet girl, remains undiagnosed, but also shows delays in her development.
Since Wang hasn't yet seen most of the children here, he spends an hour observing. After singing songs in German and English, the children break into small groups. One reviews the calendar and weather. Another learns letters. Some older boys head outside with their teacher to exercise in the snow. One boy asks Wang his name.
"Dr. Wang," he answers warmly. "I am a doctor. Do you see a doctor?" Wang leaves his business cards for the families to contact him.
This one room illustrates why Wang's job is so critical to this community.
The diseases that haunt the Amish come from "founders-gene defects," genes that date to the original 200 German-Swiss Amish who immigrated to this country in the 18th century.
Since the Amish don't allow people to marry outside their faith, at times distant relatives may marry, each carrying recessive genes for an array of inherited diseases. Some are common in the general population as well, such as hemophilia or PKU (phenylketonuria), a disease caused by a defective enzyme that results in severe brain damage in infants unless they go on a special diet. Down syndrome also appears to be more common
among the Amish. Other diseases, such as prolidase deficiency, are rare in the general population. (Since he's already found two cases of prolidase deficiency among Geauga County's Amish, Wang suspects he may discover more.)
And some diseases, still unidentified, seem to be unique to the Amish — even unique to Geauga County's Amish. The Kaufimans and Daniel Miller's children appear to suffer from a similar syndrome that has not been diagnosed. In addition, there are 17 Amish children in Geauga County who have a different unidentified syndrome.
Statistically, when a father and mother each carry a recessive gene, the couple has a 25 percent chance of producing a baby with that disorder. The likelihood of two carriers marrying increases in tight-knit communities such as the Amish. For example, 100 years ago only a few Amish may have carried a recessive genetic mutation, but the carrier rate slowly increased with each generation — a much higher carrier rate than in the general population — so the chance that two carriers of a rare disease marry and have children who are sick is much greater in this isolated population.
Five of Daniel and Katheryn Miller's nine children are handicapped; three of Bob and Mary Lou Miller's four children have special needs; and all four of Mark and Esther Kauffman's children are severely handicapped, in wheelchairs and on feeding tubes.
These families deal quietly with the grim reality of what it's like to care, day in and day out, for children who can't communicate, feed themselves or ever learn to use a bathroom. They'll never farm or work wood as their fathers do or bake scrumptious pies like their mothers. Usually, it's too difficult even to get the children into the buggy to go to church and do what seems the only possible thing under such circumstances: pray.
Deeply religious, these families believe that God will guide them in their efforts to care for their children. "We just leave it to higher hands," says Katheryn Miller.
Because she had a newborn at home, Katheryn explains, she refused to go to the hospital when her bedridden son Owen began having seizures. So Wang came to the house, called seizure specialists at University Hospitals' Rainbow Babies and Children's Hospital on his cell phone and tried to arrange for an ambulance to take Owen to the hospital. But ambulance fees aren't covered by the Bureau for Children with Medical Handicaps, the state-run program many Amish families use to help pay for medical expenses. And Katheryn didn't want her son hospitalized. Wang stayed at Owen's bedside for several hours, administering medication until the seizures passed.
Katheryn recently gave birth to a Gerber-perfect ninth child, Kristina. At almost 3 months old, Kristina follows movement in the room with her bright eyes, a sign she probably has no neurological impairment. But Katheryn knows that several of her other children seemed fine in early infancy, too. Then, around four months, something happened.
She hopes Dr. Wang will someday figure out what that something was.
Wang pulls a cherished card with a rose on it from a kitchen drawer in his Solon home. The card was among the first things given to him by an Amish family. "We won't expect miracles," it reads in part. "We will just expect you to do your best and do what you can with God's help. We are very happy you are religious."
The Wangs attend the Cleveland Chinese Christian Church in Richmond Heights. Christianity, Wang says, does not play a direct role in his relationship with the Amish, but he feels it did influence his decision to come to Middlefield. "My wife and I still believe it was an opportunity God gave us to learn the love and hope, giving and caring, humility and faith from the Amish and those parents of special-needs children," he says.
He and Jan moved into this home in August, three days before school started for their daughters, Wendi, 10, and Andi, 6. They chose this neighborhood because it's in the Orange school system and sits halfway between his office in Middlefield and University Hospitals, where he hopes to obtain admitting privileges.
Wang's home, in one of Solon's most affluent neighborhoods, seems more than a world away from Huoqiu, the small Chinese town where he grew up as the youngest of five children and his parents' only boy. When Wang was young, he, like his Amish patients, lived without electricity. His parents raised honeybees to supplement their low income. On Sundays during the honey harvest, he walked miles to the countryside with his father to help. Many of his relatives were farmers, so he's comfortable with the rural life of his patients.
He has done his best to reach out to them. He began to learn German (his fifth language; he's fluent in English, French and Chinese, and reads some Japanese) before coming to Middlefield, since most of his young Amish patients don't learn English until they go to kindergarten. Patients have warmly welcomed him into their homes. His daughter Andi celebrated her sixth birthday in July with a ride in an Amish buggy.
***
The story of Das Deutsch Center really starts in 1998.
Esther Kauffman read an article in Reader's Digest about Dr. Holmes Morton, who started a clinic in Lancaster County, Pa., to try to unravel many of the mysterious genetic and metabolic diseases that plague Amish and Mennonite families there.
Since opening his clinic in 1990, Morton has identified numerous metabolic and genetic diseases, including 12 that originate from founders-gene defects. Some — including one called glutaric aciduria that Morton discovered for the first time in the Lancaster Amish community — can be treated through a special diet if they're detected early enough.
Thinking Morton might be able to give her some answers, Esther called together other Geauga County Amish families who have children with special needs. The Kauffmans, the Millers and two other families decided to visit Morton's clinic. In December 1998, JoAnn Leach and her husband Don, who has since died, drove two vans filled with the four sets of Amish parents, each bringing one of their special-needs children, to Lancaster County.
A few months later, Morton and his wife, Caroline, visited the families in Geauga County. Even with his vast knowledge of the diseases that affect the Amish, Morton couldn't tell them what had caused their children's handicaps. It would take more time than he had to give. More time than doctors at University Hospitals and the Cleveland Clinic Foundation had to give.
So the families worked with local medical professionals to put together a board of directors (headed by Tom Stone, principal of Huntsburg Elementary School and director of special-education programs for Cardinal Local Schools, Middlefield's school district) and launched the nonprofit Das Deutsch Center in 1999. It received its first grant in 2000: $65,000 from the Cleveland Foundation to hire project coordinator KC Henry Bergman. In April 2002, Wang spent time with Morton to learn more about his clinic, then started at Das Deutsch in May.
In Middlefield, Wang works in a cramped temporary office in the Evans Medical Center in the heart of downtown. Two desks are jammed into the small office. Cans of baby formula are stacked on the floor around the office.
Through a $10,000 grant from the Geauga County Christ Child Society, Wang has already started a nutrition program. Special formulas are necessary for children with digestive problems, common among those with complex medical needs. Some Amish families depend on WIC (Women, Infants and Children) to pay for special formulas — which can cost up to a staggering $800 per month — but other families refuse the government program and insist on paying themselves. While families will still have to pay for formula, the Christ Child Society grant covers the cost of extra nutrition consultations.
Das Deutsch center, which opens next month, will offer far more room. Getting the clinic built has meant hours of dedicated labor by Amish men and the donation of materials from area businesses to renovate an old home on Route 528 into a modern medical facility with exam rooms and a research lab.
But money hasn't been easy to come by. The Das Deutsch Center is in the midst of a fund-raising campaign with a goal of $1.8 million. That includes about $800,000 for start-up costs such as purchasing the clinic building and hiring staff and $1 million to fund an endowment to continue operations indefinitely. So far, the center has raised about $852,000 — including $72,000 from the Amish community, much of it from anonymous donations through church collections.
That means that before it has even officially opened its doors, Das Deutsch Center is still in desperate need of funding to survive.
Without Das Deutsch Center, the Amish might never obtain proper treatment for many of the diseases that plague their community. It can be hard for them to get enough medical care, since they don't believe in health insurance or Social Security.
They've also had to be careful about trusting outsiders. For years, "medical tourists" (as Morton calls them) have come to Amish communities to run genetic studies, take the information and leave families with nothing. Some medical tourists are doctors, but others are quacks. One man, not licensed as a doctor, became known locally as the "parasite man" because he would examine blood samples from the Amish in exchange for a donation, often declare that they had a wormlike micro-organism in their blood, and suggest that they take vitamin supplements. The man was also a vitamin salesman.
Physicians at area hospitals have done what they can to help the families. Dr. Max Wiznitzer, a pediatric neurologist and director of the autism center at Rainbow, has been one of the most dedicated. When he noticed a high no-show rate among his Amish patients, he started holding state-supported clinics in Geauga County so families wouldn't have to spend up to $75 for a round-trip taxi ride to the hospital.
At times, Wiznitzer and his pediatric nurse practitioner, Kathy Maxwell, have made house calls to families. Wiznitzer, who serves on Das Deutsch Center's medical advisory board, even met with the elders of the Amish church to convince them to give families permission to use the Bureau for Children with Medical Handicaps, the program that pays medical bills for special-needs children. In exchange, the Amish hold an auction each year and give the money to BCMH.
Still, there's only so much physicians removed from the insular Amish community can do. That's where Wang comes in. He's joined Wiznitzer to work with doctors in England who may be close to identifying the genetics involved in the syndrome that afflicts the Kauffman and Miller families.
Wiznitzer says such successes will only happen with someone leading the way.
"I see Dr. Wang as the conductor of an orchestra," he says.
It was Wang's orchestration, in fact, that led to the discovery of prolidase deficiency in two children and may have solved the mystery behind the death of Mary Smith.
The Smith children and the 8-month-old boy who shares their disease were treated by specialists at two different Cleveland hospitals, so there was no one to compare notes. They did, however, have the same primary-care physician: Dr. John Tumbush, a Das Deutsch Center board member.
Tumbush referred the Smiths to Wang, who spent hours reviewing Mary's medical records, but came up with nothing. Then, Tumbush also referred the 8-year-old to Wang. In his chart, Wang discovered an odd result from a genetics test. He called David Lundgren, a biochemistry professor who heads the lab at MetroHealth Medical Center that processed the test. Wang asked Lundgren to repeat the study on the little boy's urine.
Lundgren already had, just to make sure. "In 22 years and 7,000 patients, I've never seen this before," says Lundgren.
The urine showed astronomical amounts of imidodipeptides, a small piece of protein. In fact, the little boy's specialist hadn't believed it either, since it's so rare and antibiotics in the urine can mimic the results. The test proved that the little boy had prolidase deficiency.
Wang consulted with physicians in Canada, Arkansas and Oklahoma to learn more about prolidase deficiency. It;
occurred to him that it could be the same disease that had killed Mary Smith. That's when he anxiously went to the Smith home that September day for a sample of Jacob's urine. The sample indicated that Jacob, too, had incredibly high levels of imidodipeptides — proof that he also had the disease.
***
It's now November and Wang, armed with new knowledge, returns to the Smith home to get a urine sample from Jacob's older brother. Michael, 4, suffered from medical problems at birth, but Elizabeth always thought his symptoms were different from Mary's or Jacob's. Wang wants to be sure.
Elizabeth sits quietly at a large kitchen table, watching Wang exam Michael. Jacob and a visiting cousin, about the same age, squirm and giggle on the nearby couch. Next to the table, a pair of Scooby Doo slippers sit by a wall rack that holds black coats and a straw hat.
"How do you pronounce that disease?" Elizabeth softly asks Wang. He starts to explain, but with his thick Chinese accent and Elizabeth's limited knowledge of science (most Amish stop going to school after eighth grade), she still looks puzzled.
"Let me start over," he says. He takes out a piece of paper and draws as he explains to Elizabeth how protein is broken down into amino acids. Through urine, Jacob loses the amino acid that plays a role in keeping skin and other organs in the body healthy, he says. Elizabeth nods.
He gives Elizabeth a bottle of vitamin C pills for Jacob. He will eventually start Jacob on manganese as well, confident that these two supplements should help the boy fight off deadly infections.
About a week later, Wang has his answer from Lundgren at MetroHealth: Michael's urine is clear. For a change, he gets to give some good news to a family.
But he knows that every day he will confront new mysteries. "It is sometimes hard to forget about the puzzles I have at work," Wang says. "There are many more things I do not know than I know. I have more questions to answer than the answers I already have. I am learning to live with it, while I try to get the answers."
It's those answers that have this community counting so heavily on Dr. Wang.
