Rachel Hyman was the picture of health—a fit, middle-aged mom who was careful about her diet. So when her blood sugar started to rise, she was confused. Determined to fix the problem, she doubled down on her healthy habits, cutting out sugary foods, running almost every day, and reducing her carb intake.
"There were a lot of salads," recalls Hyman, a clinical psychologist living just outside Seattle.
But nothing worked. Her numbers kept creeping up, and soon, her glucose levels officially tipped into the "prediabetic" zone. When she was diagnosed with type 2 diabetes at age 48, Hyman begged her doctors for six more months before she had to start medication.
"I was frustrated with my body, and I wanted to do something myself," she said.
Her doctor, however, refused. Hyman’s uncontrolled blood sugar was too dangerous, and without medication, the damage to her body could be severe.
"I was really upset," Hyman said. "I just didn’t fit the profile of someone with Type 2 diabetes."
At the same time, Hyman began noticing she couldn't distinguish colors. She'd often ask her kids if clothes were blue or green. Her husband joked, "On your tombstone it'll read, 'What color is that?'"
That conversation was the beginning of a medical odyssey that would eventually lead to a frightening diagnosis: a life-threatening disorder so rare that few doctors had ever seen it. It took a misdiagnosis and a handful of physicians to figure it out, but when they did, it was both terrifying and a relief.
"A diagnosis for people is peace of mind, even if it’s a terrible thing," said Hyman, who is now on an experimental treatment plan that may help. "Without it, I’d still be treated like I have type 2 diabetes, which isn’t what I have."
A Misleading History of Diabetes
Hyman, now 54, had never been diagnosed with a serious illness until she became pregnant with her first child at age 31. She was diagnosed with gestational diabetes, a condition that occurs during pregnancy when hormones shift dramatically and the body struggles to produce enough insulin. After she gave birth, the condition resolved, as is often the case. The same thing happened during her second pregnancy.
When she was pregnant with her third child, doctors, assuming she would develop the condition again, ordered insulin injections to keep her blood sugar in check. Studies show that people with gestational diabetes are at a higher risk of developing type 2 diabetes. Indeed, after her third pregnancy, Hyman’s blood sugar remained high, and her A1C—a measure of glucose in the blood over several months—entered and stayed in the "prediabetic" zone.
For ten years, she stayed vigilant, keeping her weight steady. But her blood sugar eventually rose into diabetic territory, seemingly impossible to control through lifestyle alone. She finally agreed to take metformin, a standard medication for type 2 diabetes.
Hyman’s husband, Garrett, a sports and spine doctor, had always been suspicious of the diagnosis. "I always thought Rachel’s diabetes didn’t make sense," he said. "She was eating better than anyone."
Middle-Aged Color-Blindness
Hyman’s vision problems gradually worsened. She recalled "seeing colors differently than other people" when she was younger, but the deterioration became much more apparent in her 40s. After she complimented a friend on a pair of "good, off-white pants," and the friend replied, "They're green," she went to her ophthalmologist.
A color-blindness test, called the Ishihara test, revealed she could not see numbers embedded in a colored background that people with normal vision can easily spot. The doctor told her she was "severely color deficient." When Hyman said she remembered being able to see the numbers on the same test years before, the ophthalmologist referred her to a specialist, citing concerns about a potential eye or brain disease.
In March 2023, Hyman met with Bonnie Keung, a neuro-ophthalmologist at Swedish Hospital in Seattle. After an exam, Hyman learned she had "pale optic nerves," which indicates possible damage or an underlying condition affecting the nerves that connect the eyes to the brain. Healthy optic nerves are pinkish, but Hyman's were faded and partially white. Keung ordered genetic tests and an MRI to check for problems like a mass in the brain.
"I was scared they’d find something no one was looking for," Hyman said.
A Terrible and Rare Diagnosis
Hyman’s MRI was normal, but when Keung viewed the genetic test results, she was "truly surprised."
"I thought she would have one of the more common inherited optic neuropathies we see," Keung recalled. "[Hers] is a rare condition even in the world of neuro-ophthalmology."
Hyman tested positive for Wolfram syndrome, an incurable genetic disorder that can affect blood sugar regulation, vision, and neurological health. It affects approximately one in 500,000 people worldwide. In its classic form, patients face a bleak prognosis: childhood diabetes, optic nerve atrophy, and other debilitating symptoms like the loss of bladder control, anxiety, depression, and trouble swallowing and breathing. The median life expectancy is about 30.
When she received the diagnosis, Hyman immediately started searching online. "What I found looked awful," she said. "This was not good, and I was scared and confused." She thought about a first cousin, also 54, with type 1 diabetes who is legally blind.
"I wondered, 'Was that going to be me?'"
Hyman was so distressed that she mistook the word "morbidity," which refers to the impact of an illness on a population, for "mortality," which is the death rate.
"I’m reading about this high mortality rate and freaking out and I show my husband, ‘Oh my God, look at this,’ and he says, ‘It’s morbidity, not mortality.'"
Keung quickly arranged a meeting with a Wolfram specialist, but the week leading up to the appointment was stressful. Hyman couldn’t concentrate, lost her appetite, and couldn’t enjoy activities.
"You’re kind of holding your breath," she said. "Who wants to be the person with the super rare condition? Who’s going to want to do anything to help? There’s probably no research, and who knows what my future holds?"
A Milder Variant and a Glimmer of Hope
Anxious, Hyman logged on to that first meeting in August 2023 with Fumihiko Urano, a medical geneticist and professor at the Washington University School of Medicine in St. Louis. Urano is the director of the Wolfram Syndrome and Related Disorders Clinic, the only center in the United States that studies and treats people with Wolfram syndrome, which is characterized by mutations in the WFS1 gene.
Urano delivered some reassuring news: It appeared Hyman had a milder variant of Wolfram that mainly affects Ashkenazi Jews, whose ancestors, like hers, came from Eastern or Central Europe. Researchers only began to understand this variant recently.
Urano said that in 2015, he started noticing that a few of his Jewish Wolfram patients had milder, later-onset, less debilitating symptoms. Then, in 2018, he got a call from a Jewish genetic testing lab in Brooklyn asking about a specific mutation in the WFS1 gene that appeared among their diabetes patients.
"Something clicked," he said. "We all realized the same thing at the same time."
Urano estimates that about three percent of Ashkenazi Jews are carriers for the variant. For a child to develop Wolfram syndrome, both parents must be carriers, giving the child a 25 percent chance. Hyman's husband, Garrett, who was tested and is not a carrier, said it’s difficult not knowing the trajectory of his wife’s condition. Although her current symptoms—including blood sugar dysregulation, vision problems, and bladder issues—are manageable, it’s unclear whether these and her overall neurological health might worsen.
"My worry is whether Rachel will struggle with more impairments over time that lead to disability," he said.
Today, to try to slow the disease's progression, Hyman takes supplements: tauroursodeoxycholic acid, or TUDCA, and idebenone. Both have shown potential benefits in animal and human cell studies, said Urano.
Clinical trials are underway to evaluate possible treatments. Urano is trying to enroll 1,000 Ashkenazi Jewish patients for a trial to gain a more detailed clinical picture of the Wolfram variant that affects Hyman. But that has been challenging because few Ashkenazi Jews have even heard of the condition.
"Right now, more rabbis know about Wolfram than endocrinologists," said Irl Hirsch, an endocrinologist and professor at the University of Washington’s medical school in Seattle. He's part of Hyman’s treatment team.
Hirsch prescribed the GLP-1 drug Ozempic, which is used to treat type 2 diabetes. It's been found to mitigate certain Wolfram-related symptoms in preclinical findings and has returned Hyman to the prediabetic zone.
Finally receiving the correct diagnosis motivated Hyman to urge her family to get tested. Her first cousin, who is blind, tested positive and is now taking experimental supplements. Hyman’s mother and children, ages 22, 19, and 16, are also carriers.
These days, Hyman and her mother are advocating for more research and education. They're building a website for people to better understand the condition and pushing for JScreen, a leading genetic testing company, to add this variant to its panel.
Meanwhile, Hyman isn't peering too far into the future. "I have a good outlook," she said, but "life is uncertain. I don’t even know what’s going to happen when I get in the car tomorrow."
0 Comments