ORGANIZATION SPOTLIGHT

STRENGTH IN NUMBERS: National MPS Society members gather during a recent 5K Run. The National MPS Society organizes dozens of family centered events each year to raise awareness and help cure, support and advocate for MPS and ML.

NATIONAL MPS SOCIETY

BY LESLIE URDANETA

"'Don't Google this.' That's what they told us. I'm a nurse, so I knew when they said that – well, I knew I shouldn't look it up. My husband did, though. We were in shock. We couldn't process anything."

Titus Barrett-Weber was diagnosed with mucopolysaccharidosis type I (MPS I) before he left the hospital. Born in Kentucky in 2019, Titus was screened for MPS I at birth. After a short NICU stay, he was discharged and carried to an office down the hall, where his parents met with a geneticist and received the news that newborn screening detected the rare genetic disorder.

MPS diseases are lysosomal storage disorders, conditions where the body lacks a specific enzyme to break down cellular waste. This waste accumulates as storage within cells and causes progressive damage to the body. There are seven different types of MPS, some with subtypes within those, and all fall within a spectrum of severity from attenuated to severe. MPS diseases are considered progressive and degenerative as more buildup occurs. Without treatment, many individuals face significant symptoms and a shortened lifespan.

"Titus was the second baby to be diagnosed with MPS I in Kentucky. He has Hurler syndrome, the most severe form," shares his mother, Charlotte. "Only two babies diagnosed so far with newborn screening in our state may not seem like too many, but to be that parent that gets a diagnosis so early, it's a huge deal. Titus was nine days old when we got the news. Longer times to diagnosis mean increases in symptoms and additional risks associated with treatment options. Titus started treatment before physical symptoms even started to show up.

Today, Titus is a rambunctious 18month-old with a bright smile who loves the water, dogs, and playing in the dirt. He just returned from a recent trip with a new passion for sand and running on the beach. Titus received a life-saving hematopoietic stem cell transplant at three months of age to halt the impact of MPS I on his body and brain. Living in a small town in rural Kentucky, local doctors had never met anyone with MPS, making the road to diagnosis one that takes several years for many families. Newborn screening created a different path for Titus.

The National MPS Society ( mpssociety.org) exists to cure, support, and advocate for MPS and mucolipidosis (ML). Individuals with these diagnoses and their families connect with the Society for the most up-to-date information on research, to access resources and family support, and to engage in advocacy efforts. The Pathways pro "The National MPS Society exists to cure, support, and advocate for MPS and mucolipidosis. STRENGTH IN NUMBERS: National MPS Society members gather during a recent 5K Run. The National MPS Society organizes dozens of family centered events each year to raise awareness and help cure, support and advocate for MPS and ML. nine days old when we got the news. Longer times to diagnosis mean increases in symptoms and additional risks associated with treatment options. Titus started treatment before physical symptoms even started to show up. Today, Titus is a rambunctious 18month-old with a bright smile who loves the water, dogs, and playing in the dirt. He just returned from a recent trip with a new passion for sand and running on the beach. Titus received a life-saving hematopoietic stem cell transplant at gram offers direct, targeted support for families throughout the first year of diagnosis, including a face-to-face visit to assist in establishing services and long-term care, provide information and education about treatment options, and ensure connection into the community. Other programs provide support for medical travel expenses, durable medical equipment not covered by insurance, educational and conference scholarships, and for items needed throughout the journey.

In 1998, two-year-old Zach Stockin sat in a waiting room for an appointment for evaluation of a hernia and chronic ear infections. As a doctor passed through, he saw Zach and recognized symptoms consistent with MPS. Testing confirmed a diagnosis of MPS II, Hunter syndrome, in the toddler. His sister, Kristin, reflects on her memories of that time: "The doctors told my mother things about Zach that were awful. There were no cures, not even anything for treatment, and he already had so many symptoms. They said they could do things to help some of the symptoms, but I can't even say the things that they told us about MPS. It was so bad."

Kristin was Zach's best friend: "We were obsessed with each other, and so close. I remember how much he loved simple little things, which brought him so much joy. His favorite thing was to go to the store and use money, which he called 'buy,' to get groceries and other small items. Zach played t-ball and loved animals." As he got older, the impacts of MPS II became more evident in both his brain and body. He developed more physical symptoms and talked less and less.

When Zach was ten years old, enzyme replacement therapy (ERT) was approved and made the standard of care for treatment for MPS II. Kristin recalls changes when he started treatment, as some of the buildup from the cellular waste began to decrease: he felt better overall, little bumps on his skin ("pebbling") from deposits smoothed out, and he did not get sick as often. Though ERT could not undo the damage done to his body by MPS II, it slowed progression for several years before his body started to decline and he passed away. Zach packed a full life into 19 years, visiting theme parks, going backstage to meet Batman, helping with attendance at school, and making friends everywhere he went.

Most types of MPS follow autosomal recessive inheritance patterns, meaning both parents are carriers of genetic mutations that combine for an individual to have MPS. However, MPS II is X-linked and only the mother is a carrier. Males have a 50/50 chance of having a diagnosis of MPS II, and females have a 50/50 chance of being a carrier of the mutation for MPS II.

Kristin found out about her pregnancy and was faced with an additional challenge: she had never been tested to see if she was a carrier for MPS II. "I didn't know if I was a carrier, and I didn't want to know," she shares. "It was too hard to think about. When I got pregnant, it was only then I learned I carried the same gene that caused Zach's diagnosis. I had an ultrasound that showed I was pregnant with a boy and learned halfway through the pregnancy that he would have MPS II as well."

Prenatal diagnosis allowed Kristin several months' time to develop an action plan before her son's birth. She began receiving additional prenatal care, now with added conversations about her son and his immediate needs. She set up appointments with medical providers who cared for Zach, now preparing to care for her own son. Things were different this time, almost 20 years after her brother's diagnosis. Charlie was born with options. Before him were choices for ERT, clinical trials, and other treatments. At a few weeks of age, Charlie started ERT and received a hematopoietic stem cell transplant, similar to Titus. "The age of diagnosis, before birth, opened up a lot of avenues that people don't have. That is the big thing. The reason people get diagnosed with MPS is because things are going wrong. For Charlie, nothing was going wrong yet. He had no symptoms because treatment started so early," says Kristin. "It's the burden of choice. I feel blessed having that burden because my brother had no choice."

Charlie is almost two years old and his transplant was successful. His body now produces the enzyme that both he and his Uncle Zach were missing. Like his uncle, he loves school; he attends a specialized, inclusive daycare program that provides supplemental therapies to ensure he stays on track and continues to advance academically and socially. He loves to play with his dad and goes swimming any time he can, and Kristin uses his story to advocate for newborn and prenatal screening options, increasing access to information for family planning and carrier testing, and states: "our decision led to us being informed. I want that for others."

A life-threatening diagnosis is wrought with emotions, and parents often share they experience a flood of grief, pain, trauma, anticipation, and fear. Others describe a sense of relief. Newborn screening has been available for some diseases since the 1960s; the concept is not new. Screening is just beginning for one syndrome type, MPS I, in some states. Early diagnosis will save lives. Whether diagnosis leads to early access for established therapies and treatment options, or allows families to consider potentially groundbreaking clinical trials, and early detection is crucial.

Parents and caregivers shared these sentiments: "It was hard, but "Screening is just beginning for one syndrome type, MPS I, in some states. Early diagnosis will save lives." it was a relief to get a diagnosis. Finally, doctors started to listen to me when I said something was wrong. We went through several months where providers told me they were ordering tests to appease me, and that I was overreacting," said Amber Mongan, mother of Maura, who has MPS I. Erica McKenzie, mother of Reagan, diagnosed with MPS IIIA, shared her thoughts: "I think, 'if only' we could have had newborn screening for MPS! The outcome would not have changed for my daughter as there is not an established and approved form of treatment yet, but we could have gotten on top of things more quickly and known what we were facing. It would have helped us to manage her symptoms." Caroline Marie Fidalgo's son, Alex Olivier, was almost two years old when he was diagnosed with MPS I: "He now has psychological, emotional, physical, and social after-effects from his 8 months of hospitalization, of all the medical appointments, treatments, and everything else, and the isolation caused by the complications he experienced after requiring three transplants before having success. People complain about the isolation caused by the COVID-19 pandemic; isolation has been our way of life for 4 years now. I think that with newborn screening, things would have gone better because they would have been taken care of more quickly."

Across the United States, babies are tested at birth for a variety of conditions. Newborn screening varies from state to state, with an increasing number of conditions being considered. The Recommended Uniform Screening Panel (RUSP) ( hrsa.gov/advisory-committees/heritable-disorders/rusp/index.html) provides federal guidelines for conditions for screening, and patient advocacy groups can nominate a condition for RUSP consideration. A RUSP nomination includes data supporting FDA-approved therapy (such as enzyme replacement therapy) and pilot studies to quantify and qualify the considerations to screen newborns. Adding conditions to the RUSP is an arduous process, requiring extensive documentation, medical support, family testimony, and advocacy efforts. The National MPS Society successfully presented MPS I to the RUSP in 2016 and earlier this year, submitted the nomination for MPS II. Currently, 20 states screen for MPS I. The "burden of choice" Kristin Stockin describes having for her son is one of hope for those with MPS across the country. Choices imply options and a sense of control amid a seemingly impossible diagnosis. Answers in days immediately after birth, before many symptoms emerge, change the landscape for a baby and family. At the National MPS Society, as we seek to find cures for MPS and ML, we continue to provide direct, comprehensive support and education, and advocate for the entire community. •

ABOUT THE AUTHOR:

Leslie Urdaneta is a licensed clinical social worker and the Family Program Director for the National MPS Society. She lives in North Carolina with her husband, daughter, and a small flock of birds. She seeks to fulfill the mission of the Society to cure, support, and advocate for MPS and ML by providing direct assistance and connection with services and overseeing family support programs, working closely with families throughout every aspect of their journey.

ABOUT THE NATIONAL MPS SOCIETY:

The National MPS Society is a non-profit organization dedicated to acting as a support group for families affected by mucopolysaccharidoses (MPS), mucolipidoses (ML) and other related disorders; increasing professional and public awareness; and raising funds to further research into such disorders. Established in 1974, the National MPS Society promotes patient advocacy, provides referrals to genetic counseling and other services, and has established regional contact families to assist new families and conduct local support meetings. Visit mpssociety.org