Justin Fugelsang and Zach Pedowitz have never met. Yet both young men were diagnosed with a rare form of Charcot-Marie-Tooth disease, called sorbitol dehydrogenase (SORD) deficiency, and both found clarity through Mayo Clinic Laboratories' innovative SORD testing. Their journeys inspire resilience, as Justin has channeled his emotions into guitar playing, and Zach has embraced educational leadership.

Justin Fugelsang, 17, of New Fairfield, Connecticut, and Zach Pedowitz, 23, who grew up in Milton, Georgia, have never met. Yet both share a love of music: Zach, a trumpeter, was active in marching band through high school; while Justin, a guitarist, currently plays in his high school jazz band. And over much of their school years, both were haunted by feelings of physical inadequacy or “klutziness.” More recently, after a long journey seeking answers, both found out they have a newly discovered type of Charcot-Marie-Tooth disease (CMT) called sorbitol dehydrogenase (SORD) deficiency, also known as CMT-SORD. Their diagnoses were clinically confirmed by a novel urine test (Mayo ID: SORD) that’s only offered by Mayo Clinic Laboratories. 

Marching to the beat of a different drummer

CMT-SORD is a form of peripheral neuropathy caused by inherited changes in the SORD gene that lead to a buildup of the sugar alcohol sorbitol. As it accumulates in the body, the buildup of sorbitol becomes toxic to the nerves. Symptoms include muscle weakness, numbness, tingling, and limb pain.

For Zach, it began on the soccer field during middle school. “That's when I started picking up that running and all that didn’t feel quite natural, but I didn't have the words to describe it,” he says. “And my coaches definitely wanted to push me.”

When Zach entered high school and began playing trumpet in his school’s marching band, his symptoms further singled him out. He did well on trumpet, having played for over five years by then, but had trouble with the choreographed marching “sets” that required foot-strength techniques.

“I had a lot of finger strength from playing trumpet,” says Zach, now in graduate school at the University of Vermont in Burlington, working on his master’s in educational leadership and policy studies. “But my foot strength was something that I just kept losing because of CMT-SORD, but I didn't know that yet because I didn't have the answers I do now. I kept getting told I wasn't trying hard enough, and I saw everyone else moving with no problem. So trying to make new friends was hard because I couldn’t match their ‘normal,’ and on top of that, I was constantly singled out for poor technique. I just grew up with a learned behavior that I wasn't trying hard enough.”

In 2019, the spring of his senior year, Zach was doing physical therapy for a prior injury when his therapist noticed his gait was off. The therapist had Zach perform some strength tests and further commented that Zach did not have the strength he should have for a male his age.

“That opened up a conversation with my parents, like, ‘Hey, something's off about this. We should look into it more beyond physical therapy,’” he says. “Over the next six months, I went through a cycle of doctors and bounced from one level of specialist to the next.”

After high school, Zach took a gap year. By the time he entered college, he had such a bad taste in his mouth from his recent marching band experience that he gave up playing the trumpet and the idea of music as a career path. “It was a hard choice to make,” he says. “Music was my identity.” 

A double ankle sprain  

Like Zach, Justin discovered his lack of foot and ankle strength while playing soccer. “I could not keep up with my friends,” he says. “I couldn't kick the ball like they could.” In seventh grade, he entered Trinity-Pawling School, where his science teacher, who also happened to be the athletic trainer for the school, “pointed out that I had drop foot,” says Justin. “But we didn't really pay that much attention to it.”

At first, Justin thought soccer must not be his sport. So he tried wrestling. But again, his symptoms impeded his ability to compete, so he also gave up that sport.

Things came to a head at school one day in ninth grade. “A friend of mine and I were messing around and I jumped off of a pedestal and basically sprained both ankles and broke my fifth metatarsal,” says Justin, who has also been diagnosed with ADD. As he walked back to school, one of those ankles swelled to the size of a baseball. “It wasn’t hurting me, but I couldn’t walk very well. I was just thinking, like, ‘What the heck is going on?’ Because obviously I'm not having the pain of someone who just sprained both of their ankles and broke part of my foot.”    

Back at school, Justin’s ankle sprains raised the concerns of his physical therapist, who suspected there was something wrong beyond his injuries. “So that kind of sparked the catalyst of going to see some doctors,” Justin says. Among them was a neurologist his parents took him to see because of his hand tremors, thinking they might be caused by his ADD. 

Two different paths toward the same answer

After a series of tests, Justin’s neurologist suspected he might have CMT but was unwilling to give his family a more specific diagnosis. So the family first went to Mount Sinai, and then to a CMT specialist at Connecticut Children’s, where Justin underwent an extensive genome test — a very expensive test the family’s insurance did not cover. Luckily, the hospital facilitated financial help from a “mystery donor.” Still, a diagnosis could not be confirmed, but the specialist referred them to Michael Shy, M.D., a neurologist at University of Iowa Healthcare Medical Center’s (UIHMC) Carver College of Medicine.

Meanwhile, Justin’s parents, Eric and Jennifer, also underwent testing. “This particular type of CMT is something that we call ‘recessive,’” says Tiffany Grider, a genetic counselor in UIHMC’s Department of Neurology, who counseled both families. “That means you have to inherit a gene abnormality from your mother and a gene abnormality from your father. And the combination of the two together is what causes the condition.”

Genome test results concluded that both Jennifer and Eric have a SORD gene variant. “But it wasn't conclusive, especially for me,” says Eric, whose SORD variant was classified as a “variant of uncertain significance.”   

So then, around December of 2023, the Fugelsangs traveled to UIHMC to see Dr. Shy and consult with Grider. “When we got out to Dr. Shy in Iowa, we had CMT definitely at the top of the list, but we still weren't sure if that's what was going on,” Eric says.  

Zach’s journey, too, led him to Dr. Shy. By then, via tests including a spinal tap, he had some clues that his symptoms were either being caused by an autoimmune issue or a type of neuropathy.

“When Zach first came to us, he actually had had a pretty extensive workup and already had an EMG, but we repeated it here,” Grider says. “He also had extensive genetic testing done, but it was not as extensive as what Justin had completed. And so this testing did not identify anything about SORD. Probably because it wasn’t in the literature for labs to be looking for it and reporting it.”

After his week of testing was over, Zach was diagnosed with CMT. Then, last October, he received another more specific update from Dr. Shy. “That’s when he told me he’d updated my diagnosis to CMT-SORD,” Zach says.

Zach was contacted because Dr. Shy’s team found the genetic abnormalities in the SORD gene through a research study.

“The research team identified the variants in SORD and then they went out and searched for samples that are in our research subjects that fit with what we know about SORD,” Grider says. “Zach’s case got identified as, ‘Oh, his clinical features would fit with the clinical features we see in others with SORD.’ So it was put in the batch of people that had genetic testing for this condition. We knew that he had a SORD diagnosis based on this research testing. But we didn’t have a way to do clinical confirmation unless we spent a lot of money doing the genetic testing. So, sending his urine sample to Mayo Clinic Laboratories helped us provide a clinical confirmation of his diagnosis.”

By the time Justin arrived at UIHMC, Dr. Shy and his team had finished the SORD study and now knew how to look for it in genetic testing. But they needed to clinically confirm his diagnosis as well — because the SORD variant he inherited from his father was not classified to be disease-causing. So, in February 2024, Justin’s urine sample was sent to Mayo Clinic Laboratories for testing. His results came back positive for CMT-SORD. 

The quest for clinical confirmation

Because it can be performed on a urine sample, Mayo Clinic Laboratories’ SORD test is less costly than genetic testing and highly sensitive at detecting sorbitol and xylitol (both sugar alcohols that are elevated in patients who test positive) in the body. Before the test was launched in February of 2024, sorbitol levels had never been measured before in urine.  

“This test is useful in that it provides biochemical evidence of disease for a genetic condition where the causative gene is difficult to analyze or may have variants of unknown significance,” says Matthew Schultz, Ph.D., a consultant in the Mayo Clinic Division of Laboratory Genetics and Genomics who developed the test method, which uses gas chromatography-mass spectrometry (GC-MS). “We started with urine testing because we had experience measuring sorbitol in urine, and so it was the fastest way to get the test out to patients to help them reach a diagnosis. For patients, providing a urine specimen is easy and this test is relatively inexpensive compared to the genetic testing, which is not always definitive.” 

The association between inherited changes in the SORD gene and peripheral neuropathy was first published in 2020. Word soon spread among neurology groups that SORD deficiency may be a fairly common cause of CMT type 2. The SORD test in urine was inspired by Jordan Bontrager, a genetic counselor at University of Rochester Medical Center, who reached out to a genetic counseling team she knew at Mayo Clinic. From there, the test’s development became a collaborative effort.

“Jordan used to work in the Molecular Laboratory at Mayo Clinic in Rochester, Minnesota, and then moved on to Rochester, New York, to provide care for patients in their neurology clinic,” says Amy White, a genetic counselor in Mayo Clinic’s Biochemical Genetics Laboratory. “When she was trying to find a test to screen her patients for sorbitol deficiency, she reached out to us and said, ‘Hey, could we try testing for sorbitol in urine?’ She and Dr. David Hermann’s inquiry led to this idea for testing.”

In order to develop the SORD assay, the lab needed patient samples. This is where the collaboration expanded to additional institutions, which White facilitated. “The University of Iowa team, as well as the University of Rochester Medical Center team and the Clinic for Special Children that works with the Plain population in Pennsylvania, were really instrumental in being willing to provide patient samples and work with us, which allowed us to develop this assay,” White says.

In the future, Dr. Schultz and his lab would also like to validate a blood test for SORD. “Validating blood would give us the ability to perform DNA testing and biochemical testing from the same sample,” he says. “It’s also a better monitoring test for a potential SORD treatment currently in clinical trials.” 

Diagnosis confirmed, what now?

For Zach and Justin, getting clinical confirmation for their diagnosis from Mayo Clinic Laboratories was a double-edged sword.  

“Dr. Shy briefed me on what my diagnosis meant,” Zach says. “I can still live a pretty much normal life, long-term, if I take care of myself, which is good.”

While there was relief, the news also left Zach in limbo about what to do and “who to be” at UVM. “Once I got to college, I kind of had to figure things out from scratch,” he says. “I had no clue what to do for a career.”

The answer unfolded when he joined a fraternity at UVM where he found not only new friends but a level of fellowship he could not have imagined.

“I had a habit of excluding myself from groups as well as not thinking I was good enough to be in leadership,” he says. “And then my older brothers in the fraternity reached out to me, saying, ‘No, we see good potential in you.’ They encouraged me to give leadership a shot, and I had a lot of wonderful leadership opportunities and memories with the fraternity, thanks to their support. That's really when I started realizing my passion for education and leadership.”

Zach continues: “It’s been hard, but I’ve worked to turn my entire outlook around on what I can do. I’ve never had that sense of ‘normal,’ but I’ve learned to take that in stride and make it a strength I am very happy with. Being able to get answers from Mayo Clinic helped me start to accept this as part of my identity and find a career I'm really passionate about. I'm excited to see where this goes.”

Zach also may be gaining a second wind for his music. “Some days, I think about playing again because it was something I enjoyed,” he says. “I'm actually waiting on my trumpet to come back from the cleaners.”  

The guitar becomes therapy

Justin, too, had a kind of self-reckoning on receiving clinical confirmation of his diagnosis from Mayo Clinic Laboratories. “I cried a bit,” he says. “I was both relieved and destroyed. Because you figure out that it doesn't matter what you do, you're just completely done. So it was really tough. But at the same time, I had this relief that was, like, ‘This explains everything. You didn't just suck at sports. You weren't hopelessly uncoordinated.’”  

For a time, Justin was “petrified” of doing anything remotely athletic for fear of injuring himself. But he’s slowly bouncing back, taking some hikes, trying to move on with his life. 

The news was also hard on Justin’s parents. “I was devastated,” Jennifer says. “I felt very guilty and I wondered, ‘What is his future gonna be like? What if it gets worse?’ I'm still sad, of course. But I find myself now wanting to be his biggest cheerleader, in the sense that I'm not gonna let him give up or not try something just because he has CMT.”

Eric, too, was racked with guilt and worries for his son. But he’s also excited, as is Zach and his family, about a new drug from Applied Therapeutics that showed promise in clinical trials — an aldose reductase inhibitor that is a central nervous system penetrant. The drug blocks the conversion of glucose to sorbitol and, by doing so, lowers sorbitol levels in the body. The inhibitor has shown potential in slowing — or stopping — disease progression in patients with SORD deficiency. The drug will hopefully be approved by the FDA in a year or so. 

As Justin finishes out his senior year, he’s found refuge in the arts, especially theater. He recently had a leading role in a school production of “A Few Good Men,” which was “the most fun I've ever had,” he says.

But he finds the most solace in going to his room and playing his guitar. “Being a senior in high school, I've got a lot of other emotional stuff going on besides worrying about my CMT,” Justin says. “So, whenever I sit down on my bed and just play my guitar, it kinda all disappears for a bit. It allows me to be in my own world and express myself.”

Justin’s father, also a guitarist, has noticed something else the instrument does for his son. “When he pushes his fingers against the fretboard, against the strings,” Eric says, “the shaking in his hands goes away.”

For more information on SORD testing from Mayo Clinic Laboratories, visit https://www.mayocliniclabs.com/test-catalog/overview/620920.