What are the symptoms of Jewish Wolfram syndrome and how are they managed?

The Ashkenazi subtype of Wolfram syndrome can present with a wide range of symptoms, which are often mild in the early stages, making diagnosis particularly challenging. However, early recognition and intervention can help lessen the disease’s severity.

This guide covers what to watch for, what to do if you test positive and how the condition may affect health, treatment decisions and family planning. Here are answers to common questions.

What are the common clinical features?

Jewish Wolfram syndrome presents with a broad spectrum of symptoms, often starting mildly in childhood or early adulthood. These may include:

• Atypical diabetes: that doesn’t resemble Type 1 or Type 2
  

• Vision problems: Damage to the optic nerve (optic atrophy) leading to blurred vision, difficulty distinguishing colors (color blindness), and, in some cases, blindness. These vision changes typically are not correctable with glasses, and are often first noticed in high school or college.
  

• Urinary tract dysfunction: Frequent urination, bladder control difficulties or increased risk of infections.
  

• Neurological symptoms: Anxiety, depression or mild cognitive changes

What does it mean to have atypical diabetes?

A key clue in identifying this condition is an atypical form of diabetes that does not fit the standard characteristics of Type 1 or Type 2 diabetes. People with Ashkenazi Jewish WFS1-associated Wolfram syndrome may exhibit a distinct diabetes profile:

• Gradual onset: Blood sugar rises slowly over time.

• Leanness: Affected individuals are often not overweight

• No Type 1 markers: They lack autoimmune markers typical of Type 1 diabetes.

• Prolonged prediabetes phase: Mildly elevated blood sugar levels may persist for years before progressing.

• Lack of lifestyle-related risks: Unlike more common types of diabetes, this condition isn’t strongly linked to poor diet, lack of exercise or obesity.

• Gradual worsening: Despite lacking these risk factors, blood sugar levels steadily increase over time. 

How can you catch symptoms early? 

Because this condition is not well-known, individuals with symptoms may go undiagnosed. Preventative medicine and early detection of the Jewish variant of Wolfram syndrome can enable faster diagnosis, earlier intervention, better symptom management and improved outcomes for those affected.

It is important to stay on top of your health, and routinely check optic nerve function with an ophthalmologist and A1C levels with an endocrinologist, to catch symptoms early if they begin to develop. 

What should you do after testing positive for the Ashkenazi variant of Wolfram syndrome? 

A positive test result for the WFS1 Ashkenazi variant can be overwhelming — but there are clear next steps:

• Create a personalized health plan

  Work with your doctor or endocrinologist to monitor blood sugar, even if diabetes isn’t fully developed.

• Get baseline vision testing

  Schedule an appointment with a neuro-ophthalmologist to check for signs of optic nerve damage.

• Join the registry

  Participation in clinical trials and registries (like the WashU patient registry) supports future treatments and may give you access to experimental options.

• Talk to your family

  Since this is an inherited condition, others in your family may benefit from testing and awareness.

What are the treatments?

While there is no dedicated therapy or cure yet, there are ways to reduce symptom severity and slow disease progression for those affected by the disease. These include:

• Personalized diabetes or prediabetes management
  Insulin or other medications for blood sugar may be prescribed to help maintain blood sugar control and prevent complications. Consult your doctor to determine the most appropriate treatment for your needs.
  

• Routine vision checkups and optic nerve testing
  Early detection of optic nerve atrophy can help preserve vision. It's recommended to consult a neuro-ophthalmologist.
  

• Regular urologic evaluations for any bladder-related concerns

  Medications for bladder dysfunction may be prescribed.
  

• Clinical trial participation
  To contribute to the search for a cure, consider joining the international patient registry hosted by WashU Medicine.
  

• Genetic testing and family planning
  If you have — or plan to have — children, your partner may wish to get tested for the Ashkenazi variant. Learn more about inheritance and planning for the future here.

Learn about the latest treatment research from Washington University in St. Louis here.

If you're of Ashkenazi Jewish descent and have unexplained or "atypical" diabetes, vision problems or urinary symptoms — especially more than one — talk to your doctor about genetic testing for the WFS1 variant. If your doctor is unfamiliar with this condition, consider sharing this informational pamphlet or website with them for more details. Early detection and proactive care can make a meaningful difference.  Find testing locations here.