Diagnosis of 2-year-old's (very) rare syndrome fuels a warrior spirit
Aug. 13—WATERTOWN — Josiah J. Cabrera, 2, is no longer a medical mystery. That designation was finally lifted eight months ago, 21 months after his birth.
On Tuesday, Josiah sported a timely T-shirt. Its back read, -oneinamillion. Its front, above a graphic of a ribbon, read "Autoinflammatory Awareness Month." Since 2015, August has been internationally recognized as AAM.
Josiah's mother, Makenzie E. Cabrera, had no plans of becoming a rare disease warrior mom, but when she and her husband Julious welcomed Josiah, their second child, duty called.
Josiah was born on March 16, 2021 at Samaritan Medical Center. From the onset of her pregnancy, Makenzie's intuition told her something wasn't right. The situation wasn't like when their other son, Jayse, arrived in the spring of 2019.
"I was really sick right off the bat with Josiah," Makenzie said, noting she became anemic and slept a lot.
"I didn't have like the normal kicking and moving around," she added.
She was diagnosed with HELLP syndrome — H: Hemolysis, destruction of red blood cells; EL: elevated liver enzymes and LP: low platelet count. For the last 18 weeks of her pregnancy, Makenzie was in and out of SMC. At 36 weeks, she needed an emergency C-section.
Her baby's heart rate approached 300 bpm. Her hemoglobin level had dropped to eight — normal level of hemoglobin is 12 to 16 grams per deciliter for women of childbearing age.
"Julious had to run and drop Jayse off at my mom's (in Pulaski) and he almost didn't make it back when I gave birth," she said.
"She was very ill during the entire pregnancy and I had to be her number one advocate," her mom, Katianne Storms, a nurse at CNY Pulmonary and Sleep Medicine in East Syracuse, said. "She had some issues when she was little, so I was kind of familiar with what kind of avenues to help her with."
With Josiah's arrival, a mystery began to envelop the lives of the family. It fueled Makenzie's frustration but also her fighting spirit, a tenacity to uncover what was ailing Josiah and a mission to help others who may find themselves or a loved one in a rare-disease situation.
A gene mutation
As Josiah ran around a city bench near the Times offices on Tuesday, it was eight months and 200 tubes of blood taken within the first 21 months of his life before an official diagnosis of his syndrome was found: familial cold autoinflammatory syndrome with a subset of Raynaud's disease. Raynaud's causes some areas of the body —especially fingers and toes — to feel numb and cold in response to cold temperatures or stress, making winters especially difficult for Josiah. "His hands get numb, burn and turn white or purple," Makenzie said.
FCAS is caused by a mutation of the NLRP3 (also known as CIAS1) gene. Autoinflammatory disease are often caused by genetic mutations that affect the innate immune system.
"Usually with these mutations, it's partial or some of the gene missing. Josiah's gene is fully missing. It's a deletion variant," Makenzie said.
FCAS occurs at a rate of less than one in a million. Around 300 people have been diagnosed with it in the U.S., Makenzie says, and from her research, believes Josiah's case is the first ever in New York State.
The Cabreras recall the day the diagnosis came: Dec. 8, 2022. It had been a 21-month journey. Makenzie sat at their kitchen table and cried. She was "not crazy." Her efforts had paid off. But it was more than a sense of relief.
"I was mad because all the pediatricians and all the other doctors were like, 'He's fine. He's normal. He's just having viruses and building his immune system,'" Makenzie said. "I have a kid who is 4. This is not normal. But nobody was listening to me."
After the diagnosis, she prepared for "huge mountains to climb." In addition to being a mom, Makenzie is a student at Jefferson Community College, with plans to graduate in December of 2024 with a four-year registered nurse degree, which will include transfer credits. She and Julious, who works at Walmart, live in Watertown. Josiah has also been diagnosed with autism and global developmental delay. His brother Jayse also has autism along with a blood coagulation defect disorder and a heart murmur.
Josiah's symptoms since birth have included rashes, fevers of unknown origin, seizures, joint pain, chronic infections, sensitivity to weather, extreme thirst and, Makenzie says, "other weird symptoms." His first symptom, days after birth, was a rash on his face and other parts of his body.
"By 11 days old, he had a seizure in Julious's arms," Makenzie said.
"With our first son, I had never seen anything like it," Julious said. "For Josiah, he was just very still and weird. I just felt something was wrong. His face and eyes? Nothing moved. It just didn't seem normal."
The couple rushed Josiah to SMC. Following initial tests, he was sent to Upstate Golisano Children's Hospital in Syracuse, where he spent 13 days in the pediatric ICU. This was during the COVID-19 lockdown, which limited access of the public to hospitals. Makenzie's husband and mother weren't allowed to visit.
"We were isolated," Makenzie recalled. "It was hard knowing my mom was right there and couldn't be with me."
At Golisano, a spinal tap showed Josiah had an infection in his spinal fluid.
"They also did a lot of blood work, which is when we found out that he had two urinary tract infections at the same time," Makenzie said.
Josiah was given antibiotics and went through a batch of imaging procedures.
But the symptoms of something unknown continued. Makenzie began a "symptom diary." Josiah was then referred to nearly a dozen specialists.
"It was so crazy," Makenzie said. "We traveled everywhere. We even went back home to New York City to get a second opinion because at first, they thought it was meningitis."
Makenzie is a native of Newburgh, Orange County and her husband is a native of the Bronx. Makenzie and her mom moved to the north country after her mom accepted a job offer at a Syracuse hospital.
Makenzie, a 2018 graduate of Belleville Henderson Central School, attended Watertown High School for a few years before moving to the BHCS district.
After being misdiagnosed for a total of five times, Makenzie and her husband sought genetic testing. But it's an expensive procedure, more than $4,000 Makenzie said, and which was denied by the family's insurance. Makenzie reached out to the Jeffery Modell Foundation for Primary Immunodeficiency Disorders, which covered the bill.
The Jeffrey Modell Foundation is a public, nonprofit charity devoted to early and precise diagnosis, meaningful treatments, and ultimately, cures through clinical and basic research, physician education, patient support, advocacy, public awareness and newborn screening. Vicki and Fred Modell established the foundation in 1987 in memory of their son, Jeffrey, who died at the age of 15 from complications of primary immunodeficiency.
Newborn screening
All states are required to do newborn screening for diseases. According to the National Library of Medicine, newborn screening programs may screen for up to 50 diseases. New York State operates a screened disorders program for newborns, mostly for genetic disorders. A sample of blood from a newborn's heel is used to screen for disorders. There is no cost to parents.
Makenzie has become an advocate of expanding such testing.
"Right now, there are about 40 to 60 newborn screening disorders testing, depending on the location and testing site, none of which are autoimmune or autoinflammatory diseases," according to Makenzie.
The National Library of Medicine says that autoimmune disorders "have a complex genetic basis; multiple genes contribute to disease risk, each with generally modest effects independently. In addition, it is now clear that common genes underlie multiple autoimmune disorders."
Makenzie has become involved with Rare Disease Legislative Advocates, a program of the nonprofit EveryLife Foundation for Rare Diseases. Among its goals is to enhance newborn screening policies at both the state and federal levels to expand the number of diseases screened for at birth.
"It's unfortunate, but I'm glad that Josiah was one of the kids who got diagnosed technically early," Makenzie said. "But it was because I didn't stop. There's a lot of gaslighting in the medical community."
Makenzie has become an EveryLife Young Adult Rare Representatives member for New York. Its young members are highly motivated to instill confidence in the next generation of rare disease advocates.
She has gotten involved with Rare Disease Legislative Advocates, a program of the nonprofit EveryLife Foundation for Rare Diseases. Among its goals is to enhance newborn screening policies at both the state and federal levels to expand the number of diseases screened for at birth. She has become an EveryLife Young Adult Rare Representatives member for New York. Its young members are highly motivated to instill confidence in the next generation of rare disease advocates. She's also an ambassador for a "high risk" HELLP group and for FMF & Aid (Familial Mediterranean Fever and auto-inflammatory diseases) Global Association.
Her other advocacy work includes writing for various blogs and a guest on podcasts as she advocates for the discovery of rare diseases and the navigation of life as a special needs mother.
Makenzie said she wrote a letter to Watertown city council members requesting some sort of local designation to mark Autoimmune Awareness Month.
"I'm waiting to hear back," she said. "I want to do a day where they light up something orange." Autoinflammatory Awareness Month has an orange theme.
"Hopefully, they'll do something because it being the first case in New York, it'll be very special for us to implement something and raise awareness that way."
At 7 p.m. on Monday in Syracuse, there will be a "City Hall Lightning for Josiah & Autoinflammatory Awareness Month" as the building will be lit up orange.
Going forward
All of Makenzie's advocacy work is inspiring to Josiah's godmother and Makenzie's best friend, Katrina K. Brown of Watertown and a 2018 graduate of WHS. "I was pretty much by her side for her entire pregnancy," Brown said.
Following the birth of her godson, Brown recalls the "countless" doctor visits, phone calls and the "rigmarole" in dealings with health insurance that Makenzie navigated through.
"And the places telling her that she was crazy and their was nothing wrong with her son, all the way from day one, until last December getting the genetic testing done and finding out what all was going on," Brown said. "We were begging for almost two years looking for answers. Why is he so fussy? Why is he crying all the time? And then, her calling me the day that she found out and her just crying because she was finally happy that she had an answer and that she knew how to go forward from there."
Brown said that her uncle also has a rare disease. "I had somewhat learned about then when I was in high school and through different advocacy programs, but Makenzie has found different things and found people that have my uncle's condition just through her advocacy programs."
Expensive injections
There is no cure for FCAS but long-term medical treatment through "biological injections" is available. Josiah receives monthly injections of the drug Ilaris at the Waters Center for Children's Cancer and Blood Disorders at Upstate Pediatric Cancer Center. Each injection costs $18,000. "The injection blocks inflammation," Makenzie said. "His symptoms go down to a minimum but they don't fully go away. It's just more tolerable."
Brown has seen a huge difference in Josiah compared to when he was a few weeks old. "He's a happy-go-lucky 2 year-old, where if you were just to look at him on the street, you wouldn't know anything was wrong with him," she said.
So far, the Cabreras consider themselves lucky because the cost of the injections has been covered by insurance, but it requires work.
"Insurance luckily has covered so far, but there have been occasional times where they will deny it and we will have to fast-track appeal and then it will be covered," Makenzie said. "Unfortunately, there is no pediatric infusion center here in town. So we travel."
For traveling near and far, the Cabreras are thankful for Children's Miracle Network. It provided an all-terrain WonderFold stroller wagon to the family. Previously, Makenzie and Julious were using a stroller with its wheels and straps failing.
"It has a five-point harness and seats with a canopy to go over them because he's very sensitive to any type of weather," Makenzie said of the WonderFold. "It's been a blessing."
Josiah also has hypotonia — decreased muscle tone. "He looks like a normal kid, but he can't walk far distances," Makenzie said. "We couldn't take him around the zoo where he'd last. That wagon helps him be comfortable."
She said the wagon also helps with Jayse, an "extreme eloper."
"He will run anywhere, at any time with no sense of danger."
CMN also helps the family with financial reimbursements for their travels as they seek medical care for Josiah. The family travels to Syracuse five to six times a month for medical appointments and five to nine times every six months to facilities in New York City, Boston, Albany and other places.
"We love CMN," said Makenzie, who has become an ambassador for the organization.
There's a host of things related to Josiah's care that have been denied by their insurance.
"He needs a medical bed because he has sleep insomnia because he has pain, so he's up all the time," Makenzie said. "That bed alone cost like 20-to-30-thousand dollars. We can't afford that. They denied us six times."
Strategy and hope
Due to Josiah's Raynaud's disease, summer outings are much easier for the family, compared to winters. Trips outside in the cold months require strategy. "It's sad because our older one loves building snowmen and playing in piles of snow," Makenzie said. "Josiah can't be outside for more than two minutes. Even going grocery shopping, we can't even go down the freezer aisle sometimes because it's so cold. We have to plan and watch the weather closely."
His parents take things day-by-day, thankful for small victories as their children reach key milestones. In the coming years, Makenzie hopes there will be more drugs developed that "will help Josiah's everyday symptoms, and he's happy and healthy."
"Hopefully this rare disease doesn't become so rare anymore," she said. "I'm not saying I want more kids and adults to have it, but there are so many people who are undiagnosed because they can't afford testing."
Makenzie's fighting spirit is especially appreciated by her husband. "I've been going with her flow," Julious said. "She's been a super mom, super wife. "She's been there and I'm there as her support."
"She has a lot on her plate," her mom, Katianne Storms, said. "I think the motivation that she has behind her keeps her going. She has a very strong support system behind her. That's very helpful and she needs that — a strong side behind her and in her corner."
"Never give up," Makenzie advises others who may face a similar situation. "Even when you feel hopeless, you have to keep going. Keep researching. Google isn't always your friend, but sometimes it is."
The mysterious medical murk that Makenzie has meandered through may have been frustrating, but at the end of each day, she feels blessed.
"I'm blessed to be a mother of a rare disease warrior."
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The details
n WHAT: The Cabrera family hopes to travel to California to consult with the doctor who led research in the discovery of the mutation that leads to familial cold autoinflammatory syndrome. Dr. Hal M. Hoffman is a board-certified allergist/immunologist and chief of the Allergy, Immunology Division at Rady Children's Hospital-San Diego and UC San Diego. He has authored more than 70 original scientific publications, largely devoted to studying the NLRP3 inflammasome and innate immunity. "He is the reason why we are getting an appointment," Makenzie Cabrera said. "Hopefully by the end of the year, or beginning of next."
n FUNDRAISER: "Cabrera Family Draft Softball Games" to help with associated costs of the trip.
n WHEN/WHERE: Sept. 16 and 17 at 12022 State Route 193, Ellisburg. The address is Old Creamery Fabrics & Craft Store, but the fire department owns the field behind it. Starting time 9 a.m. both days, with games to dusk. —COST: $20 per person per day or $30 for both days. In addition to the softball tournament, there will be raffles and food.
n TO REGISTER/MORE INFO: Text or call Cabrera at 315-804-0664 or write to her at mevandervort@yahoo.com.
n ANOTHER WAY TO HELP: The Cabreras have a GoFundMe page at wdt.me/Cabreras
