Judy Kalnas remembers thinking that Jessica, the youngest of her six children, resembled the elastic-limbed cartoon character Gumby.
The summer that Jessica was 14, her large extended family rented a house on North Carolina’s Outer Banks. One afternoon Judy spotted Jessica crawling up the steep steps from the beach on her hands and knees. When she asked her daughter what she was doing, Jessica replied, “It’s just easier.”
Over the next year, Jessica seemed to become increasingly uncoordinated. Although she had been cheering for a decade, she did not make the cheerleading squad her sophomore year. Her mother learned later that Jessica couldn’t perform the jumps. Jessica joined the field hockey team, instead.
Jessica, now 31, said that at the time she realized “something was very wrong.” She didn’t say anything to her parents for fear of worrying them or having to limit her activities.
“I thought it would eventually just disappear if I did things to strengthen my legs. So I would always act like I was OK when I would fall,” she said.
Her mother, a preschool teacher, was concerned. “I would go to [field hockey] practices and watch and think, ‘Why isn’t she running like everybody else?’” Judy recalled. Later, she learned that the coach had been alarmed by Jessica’s repeated falls during practice.
Then, at her South Jersey high school graduation in 2008, Jessica tumbled off the bleachers while preparing to accept a math award.
Within days, Jessica saw a neurologist in nearby Camden.
The neurologist ruled out Duchenne muscular dystrophy, a genetic disorder characterized by progressive weakness that strikes young children, usually boys. She prescribed medication for myasthenia gravis, a rare autoimmune disease that affects the muscles and often causes droopy eyelids.
Jessica took the drug for a month but showed no improvement. Her family doctor then referred her to a neurologist in Baltimore with expertise in spinal muscular atrophy, a rare genetic disease that destroys nerve cells.
The specialist told Jessica and her parents he was fairly certain she had spinal muscular atrophy; a muscle biopsy seemed to bolster that diagnosis.
But after a year, an MRI scan showed that one part of Jessica’s brain was shrinking. “I remember everybody seemed stumped,” Judy said.
The specialist expressed doubt that she had spinal muscular atrophy and referred her to the National Institutes of Health. Jessica was seen by a specialist in hereditary muscle diseases who ordered genetic testing. The results, which took many months, stunned and bewildered the family. Jessica had Late-onset Tay-Sachs disease (LOTS), a progressive, incurable genetic illness.
‘That can’t be!” Judy remembers blurting out. “We’re not Jewish.”
For roughly a century, Tay-Sachs disease, named after two physicians who pioneered the description of the neurodegenerative disease, was believed to almost exclusively affect Ashkenazi Jews from central or Eastern Europe. One in 27 people of Ashkenazi Jewish ancestry carries the genetic mutation that causes Tay-Sachs, a rate 10 times higher than the general population.
Tay-Sachs, which typically affects infants, results from the absence of an enzyme called hexosaminidase A, which prevents the harmful accumulation of a fat in the brain and spinal cord. Babies, who are typically affected in utero, appear normal until about 6 months, when they begin to regress, eventually becoming blind, demented and paralyzed. The disease is nearly always fatal by age 5.
Since the discovery of the gene that causes Tay-Sachs in the late 1980s, screening programs and genetic counseling in Jewish communities have become routine and the number of infants with Tay-Sachs has plummeted.
Scientists now know that anyone can carry a disease-causing mutation, of which there are more than 100. Concentrations of Tay-Sachs cases have been discovered in often isolated non-Jewish populations including the Irish, French Canadians from Quebec and Cajuns in Louisiana, NIH specialists informed the Kalnas family. Late-onset Tay-Sachs, a recently discovered, less-severe variant of the disease, surfaces in adolescence or adulthood.
“It was an eye opener,” said Judy, who has Irish ancestry.
After Jessica’s diagnosis, Judy discovered something she had not previously known: Her paternal grandfather was from southern Louisiana, an area where clusters of infants called “lazy babies,” many of whom were believed to have Tay-Sachs, were strikingly common.
Unlike babies with Tay-Sachs, who have a telltale cherry red spot in their retinas, late-onset cases can be very difficult to diagnose. Symptoms and severity vary greatly and decline is more gradual. Diagnosis of the disease is made through enzyme and genetic testing.
“Not only does the average person not know about this,” said neurogeneticist Heather A. Lau, associate director of the division of neurogenetics at NYU Langone, “but my colleagues in neurology aren’t aware of LOTS.” Some people with late-onset disease have been told they have multiple sclerosis or ALS, said Lau, who treats about a dozen LOTS patients, several of whom were diagnosed in their 50s.
All forms of the disease result from the inheritance of a mutated gene, one from each parent who are both carriers. For each such pregnancy, there is a 25% chance the child will be affected by inheriting two abnormal genes, a 25% chance the child will be neither affected nor a carrier, and a 50% chance the child will be a carrier who typically shows no symptoms.
After Jessica was diagnosed, testing revealed that two of her brothers are carriers, while her sister is unaffected. Two brothers have not been tested.
Doctors at NIH referred the family to Edwin H. Kolodny, a pioneering Tay-Sachs researcher who is a research professor of neurology at NYU School of Medicine. Judy said Kolodny was encouraging and realistic as he prepared them for what lay ahead.
Treatment for LOTS is largely supportive. Jessica is enrolled in a long-term study at NIH and has participated in a research trial run by Lau at NYU of a drug not approved in the United States that may lessen Tay-Sachs symptoms.
Jessica “has good organizational skills and is quite independent and eloquent,” said Lau, who added that she does not show signs of impaired judgment that can accompany the disease.
Jessica can no longer walk without the use of leg braces and two canes. Her arms are weak and she does exercises daily and rides a stationary bike. Speech therapy has been helpful for slurred speech, which is common among late-onset patients.
“My biggest fear was: ‘How am I going to live with this? How am I going to watch this happen?’” Judy said. “The main thing is that we weren’t going to lose her.”
From Jessica’s perspective, one of the hardest things about living with her disease is the inability to drive. “The most important thing is not to give up,” she said. “Keep going.”