Lisa and Derek Mason weren’t alarmed when clinicians performed a small “heal prick” blood draw on their twin sons as part of routine newborn screening in New Jersey. A similar test had been performed on their older sister less than two years before and everything looked fine. Lisa and the twins were discharged home a few days later. Their family of five was complete.

About a week later, the family received a call from their pediatrician: the test indicated the twins, Dean and Danny, may have Fabry disease, a rare genetic condition. The pediatrician referred the family to Children’s Hospital of Philadelphia (CHOP) for further testing and encouraged them to avoid researching the condition online. The team at CHOP could better explain how the condition might affect the boys.

“I’d never heard of Fabry disease before,” Lisa says. “And even though they told me NOT to research it online, I couldn’t help myself. I was extremely concerned with what I was reading, and I tried to calm myself by thinking the test was wrong.”

Searching for answers

Two days later, the family went to CHOP’s Buerger Center for Advanced Pediatric Care and met with Rebecca Ahrens-Nicklas, MD, PhD, an attending physician, Shaney Pressley, MSN, CPNP-PC, a nurse practitioner, and Caitlin Menello, MS, LCGC, a genetic counselor. All work with CHOP’s Division of Human Genetics.

Dr. Ahrens-Nicklas, Pressley and Menello explained that the newborn screening identified both boys as having extremely abnormal levels of alpha-galactosidase A, an enzyme responsible for the breakdown and removal of certain types of fat. Low levels of alpha-galactosidase A are the key feature of Fabry disease.

Imagine your body is like a big, busy city. In this city, garbage trucks (enzymes) collect trash (fats) and take it to recycling centers. But in Fabry disease, some of these garbage trucks are broken or missing, so the trash starts piling up in the streets. Over time, this can cause damage and problems in different parts of the city. 

For those with Fabry disease, this build-up of fat can lead to symptoms like pain in the hands and feet, stomach issues, skin rashes, and problems with the heart and kidneys. Because it’s genetic, Fabry disease is something people are born with, and it often runs in families. Since there’s currently no cure, Fabry disease requires careful monitoring and life-long treatment.

Since the screening test indicated the twins had Fabry disease; the CHOP clinicians performed a cheek swab of each boy to confirm the diagnosis.

The CHOP team also scheduled appointments so the twins could be assessed by a myriad of specialists from nephrology, neurology, cardiology, ophthalmology and metabolism. It was important to get baseline details about each boy’s condition so they could compare any changes as the disease progressed.

The twins were about a month old when they began to experience a cluster of disturbing symptoms: stomach pain, vomiting, diarrhea, trouble sleeping and colic. 

Results from specialist evaluations were mixed. Nephrology and cardiology reported results within normal ranges but advised close monitoring. Ophthalmology said the boys didn’t need glasses. Neurology, however, had some concerns. Dean had low muscle tone (hypotonia), and Danny had an abnormal increase in muscle tone (hypertonia), experienced spastic movements (spasticity), rigidity and stiffness. Doctors ordered MRIs to rule out stroke as a possible cause of their symptoms. 

While tests showed neither had suffered a stroke, their condition had deteriorated, becoming more alarming. Clinicians from the Metabolic Disease Program re-evaluated the boys’ disease biomarkers at 6 months old and discovered both boys’ levels were even more abnormal. They needed enzyme replacement therapy as soon as possible.

Children with Fabry disease typically don’t require enzyme replacement therapy until age 4 or older, which brought about another challenge: the medication was only FDA-approved for children age 2 and older. 

Before Dean and Danny could receive Fabrazyme® (agalsidase beta) – the only IV medication proven to calm symptoms of Fabry disease and delay more serious issues – CHOP would need to get special approval for off-label use and convince the family’s insurance company to pay for the treatment.

Seeking treatment

“Dr. Ahrens-Nicklas and her team really went to bat for us,” Lisa says. The doctor requested, appealed and diligently rallied the family’s insurance company to pay for the IV medication. After many phone calls, emails and letters, the insurance company agreed with the clinical team that Fabrazyme was the boys’ best choice for treatment.

But before enzyme replacement therapy could begin, clinicians needed to ensure the twins’ bodies wouldn’t fight the new medication. That meant a rigid 9-week cycle of medications designed to lower the body’s immune response and allow the new medication to work properly. 

Over the following two months, the boys received a weekly series of oral and IV therapies at the hospital including immunosuppressants and intravenous immunoglobulin (IVIG), while slowly starting Fabrazyme. As Fabrazyme was increased, the boys were weaned off the immunosuppressants. They continued enzyme replacement therapy and IVIG, which helped them stay well until their immune systems recovered.

A few months into the family’s new routine of IV infusions, Dean broke out in hives and his blood pressure dropped. An allergist prescribed antihistamines and steroids to address the flare. Dean’s clinical team reexamined his care and treatments, ultimately deciding to temporarily slow the rate the IV medication entered his body and set up a protocol to prevent future reactions. 

Treatment continued every week at the hospital for more than a year, then the family transitioned to having a nurse administer the therapy in their home. Their immune systems are nearly back to normal now, and they have since stopped the IVIG.

A family affair

When the twins were diagnosed with Fabry disease, clinicians at CHOP encouraged the whole family to be tested for any of the gene variants known to cause the disorder. 

What they found changed the lives of their entire family:

• Lisa was found to also have the genetic change associated with Fabry disease. She had experienced intermittent symptoms over the years: random pain in her extremities, numbness, complex migraines and sometimes speech difficulties. After her diagnosis, she began treatment a month later with her boys. “All three of us were hooked up to IVs and I was able to breastfeed during treatment,” Lisa says. “At least we were all together.”
• Ella, Lisa’s daughter and sister to Dean and Danny, also carries the family variant known to cause Fabry disease. While she does not currently show any symptoms of Fabry disease, she is being closely monitored for when treatment may be needed. Female patients with Fabry disease tend to have more mild symptoms.
• Derek, dad of Dean, Danny and Ella, does not have Fabry disease or any of the genetic links to the disorder. During his family’s treatment, he cared for Ella and supported the family during treatments at the hospital and from home.
• Gary, Lisa’s brother, was also diagnosed with Fabry disease. Now an adult, Gary has long experienced odd symptoms including burning in his hands and feet, swelling in his legs, numbness, complex migraines and speech difficulties. Doctors had been unable to diagnose him until genetic testing revealed he also had mutations in the GLA gene. He also started treatment at CHOP but has transitioned to home care.
• Kathleen, Lisa’s mom, was also diagnosed with Fabry disease after the twins were diagnosed. Though she’d suffered a stroke early in her life, doctors could not determine a cause because she did not have any of the typical risk factors for stroke. The family now understands the stroke was due to Fabry disease.

Living their lives

Lisa and Derek’s family have all been receiving their therapy at home for more than 6 months now and are loving the transition to “their new normal.” While they have bins of medical equipment and IV poles around their house, they also have toys and music and fun. 

“The boys have a lot of energy and are so talkative,” Lisa says. “Danny loves to sing, and Dean is always dancing. They love playing in the backyard with Ella, going in the sandbox and splashing in the pool.”

Lisa and Derek hope their children can live their lives as close to normal as possible and won’t be held back due to symptoms of their disease. They are thankful newborn screening allowed the boys to be diagnosed early and to CHOP for fighting to begin treatment before permanent organ damage was done. 

“They are the first patients to be diagnosed with Fabry disease and start treatment so young,” Lisa says. “I’m hopeful my children can live long, healthy lives.”

She’s also hopeful that with more research — at CHOP and beyond — more children can be supported with breakthrough new therapies and treatments.

“I really can’t thank CHOP enough,” she added. “Dr. Ahrens-Nicklas and her team fought for us to get the treatment we needed. Shaney (Pressley) was in constant contact with us, answering questions through MyCHOP or on a call. And Caitlin (Menello) was so helpful when we were first diagnosed. She wrote a letter that we could share with family members explaining why we were encouraging everyone to be tested. That lead to answers for my whole family.”