Battling genetic diseases
The baby was in grave danger, no doubt about it. Debra-Lynn Day-Salvatore, M.D., Ph.D., director of the Institute for Genetic Medicine at Saint Peter's University Hospital, remembers the infant she saw 10 years ago as if it were yesterday.
The baby was in grave danger, no doubt about it. Debra-Lynn Day-Salvatore, M.D., Ph.D., director of the Institute for Genetic Medicine at Saint Peter’s University Hospital, remembers the infant she saw 10 years ago as if it were yesterday. He was in a coma and suffering seizures. She and her team diagnosed- and a blood test confirmed-a rare metabolic condition informally called "maple-syrup urine disease" in which the body can’t break down certain amino acids, such as leucine, that are found in most foods. Too much leucine is toxic to the brain-and produces a maple-syrup odor in the urine.
She immediately put the baby on a special amino acid-free formula and intravenous fluids. Within days he came out of the coma and the seizures stopped. His formula was adjusted every week as he grew. "We had to hand-calculate the exact amounts of proteins, fats, calories, amino acids and other nutrients his body could manage," says Dr. Day-Salvatore.
That little boy was just one of the thousands of people who have been helped at the institute, where each day the doctor and her staff are busily engaged in what she calls the future of medicine.
"The old approach was simply to treat symptoms," says the doctor, whose Ph.D. is in molecular biology and pharmacogenetics. "We look for causes. Everything in medicine has a genetic component, and a correct diagnosis can help to improve management and treatment. We look at the big picture and try to put all the pieces of the puzzle together. If you don’t consider the underlying genetics, you will miss the diagnosis."
While all of us are imprinted with genetic "road maps," the role of genetics becomes most critical for those who suffer from rare defects or diseases-or an unusually high risk of serious illness such as cancer. Thus the field of genetic medicine focuses on the evaluation, diagnosis, management and treatment of birth defects, chromosome abnormalities, hereditary disorders (including cancer), metabolic diseases and other genetically influenced conditions in patients of all ages.
"It’s a fascinating and rapidly evolving specialty that spans the course of human development," says Dr. Day-Salvatore.
The institute, launched in January 1992, is designated by the state’s Department of Health and Senior Services as a regional center for newborn screening and genetic services. "Every baby born in New Jersey is screened for 55 metabolic and other conditions that may become symptomatic in infancy or later in life," the doc- tor explains. Only about 1 to 2 percent of all tests are positive for these rare diseases. "If the baby tests positive, he or she may be referred here for definitive testing. We then can provide treatment or refer the family to a facility closer to home if necessary."
Besides Dr. Day-Salvatore, the institute employs two genetic counselors, two genetic nurse specialists and a metabolic nutritionist, along with support staff. It also features a Lysosomal Infusion Center, one of the country’s few facilities that treat lysosomal storage diseases. "They are a class of metabolic disorders, of which more than 45 are known, that involve a missing enzyme that prevents the breakdown of important complex proteins, fats and sugars in the heart, muscle, liver, bones and other organs," the doctor explains. "There is FDA- approved intravenous enzyme-replacement therapy for several of these conditions that can reverse symptoms and stop the progression of disease."
Despite the complexity of the diseases she sees, Dr. Day-Salvatore’s diagnostic approach at the institute is surprisingly simple. "I don’t use a lot of procedures and gadgets," she says. "It’s actually very basic. I take a thorough medical history and perform a detailed physical examination." But she looks for things your family doctor may not check.
"We take a three-generation family history, because we can sometimes make a diagnosis from a family pat- tern of medical problems," she says. "For instance, a family may have two generations of early-onset breast and ovarian cancer-that signals the presence of the BRCA 1 gene. Another family may have a history of migraines, diabetes, seizures and retinitis pigmentosa-that’s a metabolic disorder. And in the exam, I look at things like the spacing of the eyes, creases in the hand or body symmetry. Every body part can be measured and assessed. These signs may form a pattern indicative of a particular genetic disorder." Specific testing is used to confirm a clinical suspicion or narrow the number of possible diagnoses.
The institute’s goal is to reduce or eliminate preventable medical complications associated with genetic conditions and congenital abnormalities. The phases of this effort, according to Dr. Day-Salvatore, are accurate diagnosis, a lifetime prevention and treatment plan, and cutting-edge therapies including participation in select clinical trials. The institute may serve as a "medical home"-that is, in effect offering primary care-for some patients whose genetic conditions are severe. It also works with a complete range of pediatric and adult specialists.
Genetic counselors educate patients about their risk for inheriting and/or transmitting certain genetic conditions or traits. They also explain issues of privacy (concerns about possible discrimination by employers or insurers, for example) and what screening and testing can accomplish. For some, rare metabolic disorders limit what foods the body can process; institute professionals give these patients nutritional guidance to make life as normal as possible.
As for that baby Dr. Day-Salvatore treated 10 years ago? "Today he is an honor-roll student in middle school," she reports. "He’s healthy and active and knows what he can eat-it’s basically a modified vegetarian diet with a special formula he drinks three times a day. As long as he is careful with his diet and is treated appropriately during times of illness, he’ll be able to enjoy a normal lifespan."
Debra-Lynn Day-Salvatore, M.D., Ph.D., director of the Institute for Genetic Medicine at Saint Peter’s University Hospital, was a full-time laboratory scientist before she became a physician. Her training has included stints at the Cleveland Clinic, Harvard University, Case Western Reserve University, New York University and the University of Medicine and Dentistry’s Robert Wood Johnson Medical School.
Dr. Day-Salvatore faces a challenging array of duties as a geneticist who also specializes in managing pregnant women with rare metabolic disorders-and is a consultant for the hospital’s state-designated Regional Perinatal Center, Neonatal Intensive Care Unit and Pediatric Intensive Care Unit. "I’m on call all the time for emergencies," she says. "It’s not a 9-to-5 lifestyle. And I often have to deliver difficult news to people. It’s not for everyone."
But the rewards are substantial. "It’s intellectually satisfying," she says, "to make a challenging diagnosis early enough, with very few clues, to change the outcome and help someone lead a normal, happy, healthy life."
To learn more about the Institute for Genetic Medicine at Saint Peter’s University Hospital, please call the institute at 732-745-6659.
Jennifer Westervelt of Hillsborough studies her genetic pedigree with Debra-Lynn Day- Salvatore, M.D., Ph.D., director of the Institute for Genetic Medicine at Saint Peter’s University Hospital. Jennifer, who recently celebrated her 15th birthday, first met Dr. Day-Salvatore as an 18-month-old diagnosed with a heart condition.
How 2 key genetic problems are approached
GAUCHER’S DISEASE.
In this rare inherited disorder, says Debra-Lynn Day-Salvatore, M.D., Ph.D., director of the Institute for Genetic Medicine at Saint Peter’s, a missing enzyme causes too much of a substance called glucosylceramide to build up in the spleen, liver, lungs, bones and sometimes in the brain, affecting these organs’ function.
"I might have a patient referred to me because of an enlarged liver and spleen with no known cause," she says. First she takes a detailed health history and does a physical exam. "If I suspect Gaucher’s, I’ll also order a blood test, which can confirm the missing enzyme and identify changes in the genetic coding sequence that can tell me how severe a case it’s likely to be and how best to man- age and treat it," she says. "I may order other tests to help determine how active the disease is and whether enzyme replacement therapy can be used. If so, the therapy can halt the disease’s progression and reverse many-but some- times not all-symptoms. The genetic test also helps me decide the dose and frequency of enzyme replacement."
The missing enzyme, made in a lab, is infused through an intravenous drip, usually given in two to three-hour sessions every two weeks.
HIGH BREAST-CANCER RISK.
Here a detailed medical family history examines any cases of breast cancer or other cancers often associated with it, such as pancreatic or thyroid cancer or melanoma, and at what ages they occurred. These factors give clues as to the likelihood that gene mutation is a possible cause, and if so, which genes to test for, such as the BRCA 1 or BRCA 2. Beyond testing, says the doctor, "we talk about surveillance techniques for the patient and other family members, how to reduce controllable risk factors and how to make treatment decisions in concert with other doctors." Patients also receive support in dealing with related emotional and family issues.
