Twins Jacob Nathan and Ryland Nathan Harney were smaller than the average sack of sugar when they were born at 33 weeks on December 17 last year. But they were healthy: Ten fingers and 10 toes each, healthy wails, and, most important, no wayward gene mutation of the type that cost their older brother Nathan his life when he was only 4.
Nathan Harney, the first child of Aaron and Kathryn Harney of Downingtown, was diagnosed at 14 months with Tay-Sachs Disease, a rare and lethal inherited neurological disorder largely associated with Ashkenazi (central or eastern European) Jews. But the Harneys aren’t Jewish. Kathryn Harney is Irish and German, her husband, Irish and Italian. But through their work with a researcher at Einstein Healthcare Network, they—and Nathan—have become the new face of a devastating disease that seems to also single out the Irish and people with French Canadian ancestry. (It’s also more common in groups where there’s more intermarriage, like the Amish.)
Tay-Sachs is a particularly cruel disease. The inherited mutation that causes it creates a deficiency of an enzyme called hexosaminidase A, or hex A, that the body uses to break down waste in nerve cells in the brain and spinal cord. Although the disease begins plotting its course in utero, for a few months after birth, Tay-Sachs babies develop normally. They coo, gurgle, reach for their toys, and turn over.
The Harneys have memories of Nathan as a normal, oatmeal-guzzling, giggling baby before he was 10 months old. “Nathan was already starting to stand when he stopped progressing,” said Aaron, cuddling dozing Ryland in his arms. His photos—from the grinning infant to the toddler with unfocused eyes and slumping neck—circle the living room of the Harneys’ modest suburban home. One of those photos watched over his preemie brothers during the time they spent in the neonatal intensive care unit after they were born.
But at some point, for Tay-Sachs babies, everything changes. As the toxic substance accumulates in their cells, they deteriorate rapidly. In a matter of months they lose sight and hearing, their muscles atrophy, and eventually they become paralyzed, are unable to swallow, and develop seizures. Most die before they reach 5.
It took the Harneys months to get a diagnosis for their oldest son, and not because Tay-Sachs is hard to detect. It’s not. In fact, Nathan’s diagnosis was confirmed by a pediatric ophthalmologist who spotted a small, cherry-red dot in the back of Nathan’s eye—a telltale sign of the disease. That was when the Harneys learned that they were both carriers.
To pass on the disease, both parents need to have a copy of the genetic mutation. With each pregnancy, the couple runs a 25 percent chance of having a child with Tay-Sachs and a 50 percent risk of having a child who is a carrier. If only one parent carries the gene, there is no chance a child with have Tay-Sachs but there’s a 50 percent chance that the child will be a carrier. A carrier is healthy and has enough of the enzyme to prevent any signs of the disease. Their only risk is to pass on the gene with the mutation to their offspring.
Genetic testing revealed that the Harneys carried two different strains of Tay-Sachs. In Kathryn’s case, it was the classic Irish infantile mutation; in Aaron’s, the French Canadian strain, which appears in older children. And genetic testing is what guaranteed that Jacob and Ryland will not only not get Tay-Sachs, but that they won’t pass it on.
The Harneys’ twins were conceived via in vitro fertilization (IVF) and pre-implantation genetic diagnosis (PGD), a screening test that detects genetic or chromosomal disorders in embryos produced through IVF, done by Michael J. Glassner MD, of Main Line Fertility in Bryn Mawr. It allows parents to have only healthy embryos implanted. “We wanted it to stop here,” said Kathryn quietly, Jacob cradled in the crook of her arm, sleepily sucking a bottle. “We didn’t want our kids or our grandchildren to go through what we did.”
Although he died just three months after his fourth birthday, Nathan Harney left a legacy the Harneys are sure will make his little brothers proud. As one of the unusual cluster of cases in the Philadelphia area occurring in people of Irish descent, Nathan and his parents starred in an Einstein video drawing attention to the Irish Tay-Sachs Carrier Study, a joint project of Einstein and the National Tay-Sachs & Allied Diseases Association of Delaware Valley. Its mission: To scientifically pin down the actual incidence of the Tay-Sachs gene among the Irish, now believed to be 1 in 50. (It’s 1 in 27 for Jews and people with French Canadian roots, about 1 in 250 in the general population.)
If that 1 in 50 number is confirmed through this pilot study, doctors may be advised to recommend that couples with Irish roots be tested before getting pregnant, just as they do now with Jewish couples. Routine testing has reduced Tay-Sachs incidence among Jews by 90 percent. But there’s little awareness—and no routine screening—in non-Jewish at-risk communities.
“If you’re Jewish, you pretty much know you could be a carrier,” says Aaron. “One of the Jewish families we know said they got tested for it at summer camp. If you’re Irish you have no idea—until someone in your family gets diagnosed with it.” (Nathan’s diagnosis led Kathryn’s sister—the family historian—to an intriguing find in the family tree: Ancestors who lost children to “starvation” at around 18 months old. “There were other children who didn’t die of starvation, yet this one child would have died at 18 months, which is about when children with Tay-Sachs lose the ability to eat,” says Kathryn, whose two sisters were tested and also discovered to be carriers.)
But because the condition is so rare, lead investigator on the Irish Tay-Sachs Carrier Study Adele Schneider, MD, says it’s been hard to get traction on both enrollment and awareness.
“We want to enroll 1,000 people and so far we only have 300 to 400,” said Dr. Schneider, director of clinical genetics and the Victor Center for the Prevention of Jewish Diseases at Einstein. “It’s been disappointing. It’s very hard to educate people about a disease they’ve never heard of.”
The researchers have gone into the Irish community in Philadelphia to recruit study participants, who must be over 18 and have at least three grandparents of Irish descent. They’ve had multiple screening programs at the Commodore Barry Club “The Irish Center” in Mt. Airy, the Irish Immigration Center in Upper Darby, and at the new Haverford YMCA in Delaware County, a community where about 25 percent of the population has Irish roots.
The Harneys brought Nathan to the Penn’s Landing Irish Festival where they staffed a booth with another couple who had lost their son to the disease. The study had a presence at the recent Midwinter Scottish & Irish Festival in King of Prussia with phlebotomists on hand to draw blood. There have also been screenings in Pearl River, NY, where half the population claims Irish ancestry. One of the original Philadelphia Tay-Sachs cluster families comes from this little hamlet north of New York City. “We have teams at Montefiore Hospital in New York doing screenings and we’re working with people to go to the Boston Irish Festival this summer,” said Dr. Schneider.
On March 13, Einstein is offering free screenings at the Sober St. Patrick’s Day Party taking place at WHYY, 150 6th Street, Philadelphia, an alcohol-free event after the Philadelphia St. Patrick’s Day parade, and there will be a free screening on March 17, St. Patrick’s Day itself, at Einstein.
“We can do remote screening. Our genetic counselor, Amybeth Weaver, can do the counseling on the phone, we can send them a kit,” said Dr. Schneider. “If you have a large group, we’ll come to you. When we were looking for carriers in the Jewish community, we went to a baby shower. If a large Irish family is getting together, we’ll go there.” In fact, said Dr. Schneider, she is willing to entertain just about any idea.
Her eye is always on the prize. “Our ultimate goal is to get enough people so that we can calculate if the carrier rate is higher among the Irish,” she said. “With that information we can influence patient guidelines, which can reduce the incidence of the disease.” The Harneys, she said, “have been great spokespeople. They’re the most amazing people, I have to say. They talk about Nathan all the time. He was there, he is there. He lives on and his legacy is supporting Tay-Sachs testing.”
WPVI report here: