02-08-2025
Blood sugar rising, color-blindness and a scary condition
Rachel Hyman was a fit, diet-conscious, middle-aged mom when her blood sugar started rising.
Confused, she doubled down on her health regimen: She cut out sugary foods, ran nearly every day and reduced her carb intake. 'There were a lot of salads,' said Hyman, a clinical psychologist just outside Seattle.
Nothing worked. Her numbers kept creeping up. Soon, the glucose levels in her blood officially tipped into the 'prediabetic' zone. When Hyman was eventually diagnosed with Type 2 diabetes, at age 48, she begged her doctors to give her six more months before prescribing medication. 'I was frustrated with my body, and I wanted to do something myself,' she said. But her internist refused, saying Hyman's uncontrolled blood sugar was too precarious; 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.'
During this time, Hyman began noticing her inability to distinguish colors. She routinely asked her children whether clothes were blue or green. Her husband gently joked, 'On your tombstone it'll read, 'What color is that?''
Hyman figured it was time to discuss her diabetes and color-blindness with an ophthalmologist.
That conversation marked the beginning of a medical odyssey and a scary diagnosis — a life-threatening disorder that few doctors have seen. It took a misdiagnosis and a handful of physicians to figure it out, and when they did, it was both terrifying and a relief for Hyman.
'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.'
Hyman, now 54, had never been diagnosed with any serious illness until she was pregnant with her first child, at age 31. Doctors discovered she had gestational diabetes, a condition that occurs during pregnancy, when hormones shift dramatically, and the body struggles to produce enough insulin to handle the increased blood sugar levels. After her baby was born, the condition resolved, as is often the case. The same thing happened during her second pregnancy. When Hyman was pregnant with her third child, doctors assumed she would develop gestational diabetes and ordered insulin injections to keep her blood sugar in check.
People with gestational diabetes are at higher risk of developing Type 2 diabetes, studies show. Indeed, after her third pregnancy, Hyman's blood sugar remained high; her A1C, a measure of glucose in the blood over several months, entered the 'prediabetic' zone and stayed there.
For 10 years she remained vigilant, working to keep her weight steady at no more than 102 pounds on her 5-foot-2 frame. Then her blood sugar rose into 'diabetic' territory; she seemed unable to control it through lifestyle alone. Eventually, she agreed to take Metformin, a standard medication for Type 2 diabetes.
Hyman's husband, Garrett, a sports and spine doctor specializing in physical medicine and rehabilitation, said he had been suspicious about the diagnosis. 'I always thought Rachel's diabetes didn't make sense,' he said. 'She was eating better than anyone.'
Hyman's vision problems worsened gradually. She recalled 'seeing colors differently than other people' when she was younger. But in her 40s, the deterioration became apparent. Once, she said, she complimented a friend on a pair of 'good, off-white pants,' and the friend replied, 'They're green.'
That's when she raised concerns with the ophthalmologist. An examination for color-blindness, the Ishihara test, revealed she could not see numbers embedded in a color background that people with normal vision can easily spot. The doctor said she was 'severely color deficient,' Hyman recalled. When she shared a memory of being able to see numbers on the same test taken years before, the ophthalmologist referred Hyman to a specialist, citing concerns about potential eye or brain disease.
In March 2023, Hyman arrived at Swedish Hospital in Seattle for an appointment with Bonnie Keung, a neuro-ophthalmologist. After an exam, Hyman learned she had 'pale optic nerves,' which indicate possible damage or an underlying condition affecting the nerves that connect the eyes to the brain. Healthy optic nerves are pinkish. Hyman's were faded and partially white. Keung ordered genetic tests and an MRI to look for problems, like a mass in the brain. 'I was scared they'd find something no one was looking for,' Hyman said.
Hyman's MRI was normal, but on viewing the genetic tests results, Keung was 'truly surprised,' she recalled. 'I thought she would have one of the more common inherited optic neuropathies we see. … [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 1 in 500,000 people worldwide. In Wolfram's classic form, patients face a bleak prognosis: childhood diabetes, optic nerve atrophy and then other debilitating symptoms, such as 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 began googling. '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 by what she was reading that she mistook the word 'morbidity,' which refers to the impact of an illness on a population, for 'mortality,' 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 telehealth meeting for Hyman with a Wolfram specialist. But the week leading up to the appointment was stressful: Hyman couldn't concentrate and lost her appetite and her ability to 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.'
Anxious, Hyman logged on to that first meeting in August 2023 with Fumihiko Urano, a medical geneticist professor at the Washington University School of Medicine in St. Louis who is director of the Wolfram Syndrome and Related Disorders Clinic at BJC HealthCare. The clinic is the only center in the United States studying and treating 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, come from Eastern or Central Europe. Researchers only started to understand the variant fairly recently, said Urano.
Urano said that in 2015, he began noticing that a few of his Wolfram patients, who were Jewish, 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 3 percent of Ashkenazi Jews are carriers for the variant. Both parents must be carriers for a child to have a 25 percent chance of developing Wolfram syndrome.
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 related to Wolfram, 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 disease progression, Hyman takes supplements: tauroursodeoxycholic acid, or TUDCA, which has shown potential benefits in animal and human cell studies, and idebenone, which targets mitochondrial function, another aspect of Wolfram's, Urano said. Clinical trials are underway evaluating 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 afflicts 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 who is part of Hyman's treatment team.
Hirsch prescribed the GLP-1 drug Ozempic, which is used to treat Type 2 diabetes, among other conditions, for Hyman; it's been found to mitigate certain Wolfram-related symptoms in preclinical findings, he said, and it has returned her to the prediabetic zone. This improvement probably occurred because Hyman lost a few pounds, and these drugs may support insulin production by beta cells in the pancreas, Hirsch said.
Finally receiving the correct diagnosis motivated Hyman to urge family members 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 are building a website for people to better understand the condition and also pushing for Jscreen, a leading genetic testing company, to add this variant to its panel.
Meanwhile, Hyman is not 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.'
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