Dr. Wendy Chung, at Columbia University, uses genetics to diagnose rare and complex diseases that have eluded traditional doctors and specialists Dr. Wendy Chung is director of the Discover program at NewYork Presbyterian/Columbia University Medical Center, which uses genetics to diagnose rare and complex diseases. When patients have a disease that can’t be diagnosed, they get sent to Wendy Chung. Dr. Chung heads the Discover program at NewYork Presbyterian/Columbia University Medical Center, which uses genetics to diagnose rare and complex diseases that have eluded traditional doctors and specialists. Dr. Chung, a 48-year-old geneticist and pediatrician, says she started the program about 18 months ago after having successfully diagnosed a number of patients with genomic analysis. She sensed a need for a more comprehensive approach to caring for such patients. So far, Dr. Chung has discovered 28 new diseases—mostly rare, genetic, pediatric conditions. But finding cures is far from guaranteed. Of the hundreds of patients she has seen so far, she has been able to reach a diagnosis only about a third of the time. And fewer than 10 of the patients have been cured. Among them: A set of identical baby twins, who had been wasting away because their bodies couldn’t digest certain nutrients, are now thriving. When people liken her work to the popular TV show “House,” Dr. Chung cringes a little, but acknowledges there are similarities. “We are medical detectives,” says Dr. Chung, an associate professor of pediatrics and medicine at Columbia. “I’m more focused [than her TV show counterpart] in the sense that we are using genetic and genomic tools to be able to do this.” UNCOMMON MALADIES Dr. Wendy Chung, a geneticist and pediatrician who diagnoses rare diseases, has discovered 28 new disorders. Among them are: SLC1A4 deficiency, which causes microcephaly and intellectual disabilities and is due to defective transport of amino acids into brain cells. About 1% of people of Jewish ancestry are carriers for this recessive condition. Mutations in the KCNK3 gene cause a rare type of pulmonary hypertension. Mutations are observed in fewer than one in a million people. Deficiency of an enzyme called transketolase is a rare cause of congenital heart disease and short stature. It is observed in fewer than one in a million people. One unusual method: Dr. Chung uses gene-editing technology to reproduce in mice some of the genetic mutations associated with patients’ diseases, to test possible treatments and cures. Most of the Discover program patients are children. Often they are considered a n-of-1, the scientific term for the first patient to be diagnosed with that particular genetic mutation. “These are families that are literally the first, they are pioneers in this,” Dr. Chung says. Dr. Chung says she loved solving puzzles and mysteries when she was a child. After college, she simultaneously got a Ph.D. in genetics from Rockefeller University and a medical degree from Cornell University. She was drawn to genetics because it seemed able to produce a definitive answer when searching for the cause of an illness. She did fellowships in pediatrics and medical and molecular genetics at Columbia. Some of the diseases Dr. Chung has discovered aren’t especially rare, including a congenital heart condition and a genetic form of microcephaly common in families of Jewish ancestry, she says. Some prenatal tests now screen for such conditions. The Discover program, short for Diagnosis Initiative: Seeking Care and Opportunities with Vision for Exploration and Research, sees about three or four patients a week. Those who apply are vetted by a team that includes Dr. Chung, another geneticist, a genetic counselor, a social worker, a nurse practitioner and a program manager. The team, which also works with about 50 specialists at Columbia, combs through applicants’ existing medical records and test results. About two-thirds of people who apply to the program are accepted. These often include patients with conditions that affect multiple organ systems; have unusual, distinctive features or early onset of aging. The Discover team is more likely to be able to diagnose such patients. Those with more focused problems, such as cancer, are generally referred to a specialist. Accepted patients typically see between five and 10 specialists over one to two days and get any tests that haven’t been done yet, says program manager Joy Tanaka, who has a Ph.D. in genetics. and coordinates and manages the care. Insurance generally covers the cost of tests and doctor visits. The program has no additional charges or fees, says Dr. Chung. When the test results come back a week or two later, the Discover team meets to decide whether a diagnosis can be reached, Dr. Tanaka says. Patients are then informed of the results. Other major medical centers do similar work with their geneticists, and the National Institutes of Health has an undiagnosed-disease program. But Dr. Chung says the Discover program goes beyond genetics by coordinating with a network of specialists and following through with treatment and support of patients. Dr. Chung tempers patients’ and families’ expectations from the outset, making them aware that the team may not reach a diagnosis. And even in cases where a cause of the disease is found, there may be no treatment. In the absence of a diagnosis, the team may keep searching if they believe there is a genetic basis. Other patients are referred to specialists. The Discover program may still benefit patients and their families when no treatment is available, by connecting them with others with the same condition. Dr. Chung says this helps families feel less isolated and share experiences about symptoms, potential treatments and research programs. The program also helps patients enroll in clinical trials. Curren Ramsey, 3 years old, of Melbourne, Fla., has HIVEP2 syndrome, a rare, genetic disease. He sees multiple specialists, and is also under the care of Dr. Chung at Columbia University’s Discover program in New York City. PHOTO:NERISSA RAMSEY Curren Ramsey, 3 years old, was diagnosed by specialists in Florida with HIVEP2 syndrome about a year ago after getting whole-exome sequencing, which examines all the expressed genes in a genome to look for mutations, says his mother, Nerissa Ramsey, of Melbourne, Fla. The rare, genetic disease affects brain growth and development and causes low muscle tone. In the spring, an alert system on Ms. Ramsey’s computer notified her of a research paper by Dr. Chung. The study identified six cases of HIVEP2 syndrome, including Curren’s. Ms. Ramsey emailed Dr. Chung and the two had an hour-long phone call. In August, the family flew to New York for a clinical visit. Curren continues to see local specialists to treat symptoms in addition to being under Dr. Chung’s care. In December, the Ramseys and four other affected families will meet on their first virtual conference organized by Dr. Chung. Most of Dr. Chung’s time is spent across the street from the clinic in her research lab at Columbia University, where dozens of mice have been genetically altered to reproduce human genetic mutations she has discovered. “We’ve literally taken our patient mutations and we’ve used CRISPR-Cas9 gene technology to make these exact same mutations in our mice. We’ve done that for three different genes so far,” Dr. Chung says. “We do this very strategically for the diseases we think we could actually come up with a treatment for.” The mice with genetic mutations related to metabolism may be given a different kind of food to see whether nutritional manipulations can help treat them. Those with neurological conditions may have their brains infused with neurotransmitters or molecules they are missing. The researchers also test to see if a condition can be reversed by switching genes on and off. “It’s a journey,” Dr. Chung says. “We’re just not stopping when we have an answer of what the gene is and the diagnosis is.” Source
