Lysosomal acid lipase deficiency (LAL-D) affects fewer than 1 in 50,000 people. But when it comes to rare diseases, Michigan schoolteacher Rebecca Trendy seems to have hit the jackpot.
All 4 of her sons have LAL-D — an inherited liver disease that renders the body unable to digest fats.
“It’s been quite the medical journey for us,” said Trendy, of Port Huron. In 2006, her 2-year-old son Brendan got blood work done for unrelated eye surgery and the results came back abnormal. Further tests and a CAT scan revealed that Brendan had an enlarged liver. “They had no idea what was going on with our son. At first, they said it was a common cold. They knew he had excess fat in the liver, but there was no reason for it.”
Trendy described her family’s ordeal during a recent 40-minute webinar sponsored by the Global Liver Institute (GLI). The online event was the first episode in a new GLI series aimed at “shining a spotlight on rare liver diseases that are under-recognized and under-reported,” said the organization’s CEO, Donna Cryer.
“It is our firm belief that the partnership among clinicians, patients, families, and patient advocacy organizations can surmount just about every challenge,” Cryer said. “So many people think children don’t get liver diseases, that all liver diseases take 20 or 30 years to develop. I know personally that’s not true, being 26 years post-transplant myself. The centrality of the liver and its over 500 functions is part of our essential messaging.”
Read more about lysosomal acid lipase deficiency
Cryer and Trendy were joined on the webinar by Don Wilson, MD, a pediatric endocrinologist at Cook Children’s Medical Center in Fort Worth, Texas. Dr. Wilson, who’s also secretary of the Foundation of the National Lipid Association, explained why LAL-D is so life-threatening.
“When you eat a meal, the liver has to digest the various nutrients and send them to various cells to be processed,” he said. “In LAL-D, what’s missing is the enzyme that digests the fat once it’s in your body. In essence, that fat is trapped in the liver and starts causing problems, eventually causing scarring. It upsets the entire equilibrium, so it’s a multisystem disease.”
The median age of onset of LAL-D is 5.8 years, though the disease affects patients of all ages. In infants, LAL-D can be fatal — and before a treatment was available, babies commonly didn’t survive beyond 6 months of age.
Struggling to Find Answers
Historically, LAL-D in infants was called Wolman disease, in honor of Israeli researcher Moshe Wolman, who along with his colleagues first described the condition in 1956. In fact, early-onset LAL-D occurs far more frequently among Jews of Iranian origin (1 in 4200 newborns) and in certain areas of Israel’s Galilee region.
“It was a devastating disease characterized by a very large liver and failure to thrive,” Dr. Wilson said. “With LAL-D, it can be very difficult to recognize the symptoms, even for physicians.”
Rebecca Trendy discovered that essential truth the hard way.
Both she and her husband, Scott, are carriers of LAL-D, meaning there was a 25% chance they would pass the disease on to a child. But all 4 of their sons — 23-year-old Dakota, 20-year-old Charles, 17-year-old Brendan, and 16-year-old Alec — have LAL-D. The Trendy brothers represent the world’s only known case in which all 4 of 4 siblings have the disease.
The question was why.
“We had our house tested for mold. There was none. Then we thought maybe we were doing our diet wrong, and sure enough everything was fine,” she said. “Every time they did more tests, they would come back with absolutely nothing. The kids were on medications for their cholesterol, but nothing would seem to work. They’d do EKGs and stress tests on the boys, and all that showed they were completely healthy. The doctors were frustrated because they didn’t know what else to test for.”
After nearly 4 years, the Trendys decided to take a break from all the tests. But in 2014, Dakota got sick again.
At that point, the family was referred to Dr. James Maciejko, a lipid specialist at St. John Hospital (now Ascension) in nearby Detroit. Having studied LAL-D briefly as an intern, Dr. Maciejko immediately suspected this was the source of the problem.
“He did a complete exam on all the boys and a complete background check. He did a simple finger poke, a couple drops of blood on a little card. And within a week, we had a diagnosis,” she Trendy said. “As a mom, after 9 years of your kids having blood draws and biopsies, that was the biggest relief I’ve ever had in my life. I just sat and cried.”
An Improved Quality of Life
Fortunately, that LAL-D diagnosis coincided with a Phase 3 clinical trial for Kanuma® (sebelipase alfa), an intravenous enzyme replacement therapy developed by Alexion Pharmaceuticals.
Thanks to intervention by Dr. Maciejko and his colleague at St. John, pediatric gastroenterologist Hernando Lyons, MD, the Trendy brothers got approval to start receiving Kanuma in October 2015, a few months before its approval by the US Food and Drug Administration (FDA).
Within 2 years, their mom said, “we really started seeing an improvement.”
In a 2015 press release, Barbara K. Burton, MD, lead clinical trial investigator at Northwestern University’s Feinberg School of Medicine in Chicago, Illinois, described Kanuma as “the first approved therapy that treats the underlying cause of the disease.”
“In the absence of treatment, LAL-D is nearly always fatal in infants and puts pediatric and adult patients at high risk of vital organ damage and premature mortality,” explained Dr. Burton, an attending physician at the Ann and Robert H. Lurie Children’s Hospital of Chicago. “In clinical studies, 67% of infants who received enzyme replacement therapy survived beyond 12 months of age, and children and adults had meaningful improvements in multiple disease-related liver and lipid abnormalities.”
Yet the Trendy family’s health issues are far from over. A few years after starting Kanuma therapy, Brendan developed a strong heart murmur and had to stop participating in school sports. That led their doctors to retest all 4 brothers. Sure enough, all were found to carry the same genetic defect, which Trendy said may or not be supravalvular aortic stenosis — and which may or may not be connected to LAL-D.
“Now we’re dealing with a second rare disease, and there’s nothing for this. They don’t actually have a name for it,” Trendy said. “Open-heart surgery is really the only way to fix this, and that’s not something you want to put your kids through, especially when it’s not yet 100% necessary.”