Delayed Recognition of Wolfram Syndrome Frequently Misdiagnosed as Type 1 Diabetes with Early Chronic Complications

Abstract

Delays of at least 7 years occurred before recognition of WFS among a cohort of pediatric patients with diabetes. All patients with WFS were primarily misdiagnosed as having type 1 diabetes.

Identification of a missense variant in the WFS1 gene that causes a mild form of Wolfram syndrome and is associated with risk for type 2 diabetes in Ashkenazi Jewish individuals

“…It is, therefore, less likely to be diagnosed clinically. Some individuals with Wolfram syndrome are misdiagnosed as having type 1 diabetes in the absence of optic atrophy [13,14]. A diagnosis of Wolfram syndrome is important since it can allow for a comprehensive clinical evaluation for phenotypes associated with Wolfram syndrome, clinical monitoring and management of auditory and ocular phenotypes.…”

“…Many individuals with Wolfram syndrome are misdiagnosed as having type 1 diabetes in the absence of optic atrophy [13,14]. Identification of Wolfram syndrome in individuals diagnosed with diabetes in childhood or adolescence is important since the management and prognosis of Wolfram syndrome is different to that of type 1 diabetes.…”

ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents

“…Other typical clinical features, such as sensorineural deafness, central diabetes insipidus, urinary tract dysfunction, and neurological symptoms develop later in a variable order even within the same family . Many patients with WFS are initially diagnosed as having type 1 diabetes; subsequent loss of vision, which occurs approximately 4 years after diabetes diagnosis, may be misdiagnosed as diabetic retinopathy . Patients with WFS die at a median age of 30 years, mainly from neurodegenerative complications.…”

“…AE macroglossia AE developmental delay AE umbilical defects AE congenital heart disease DEND, developmental delay, epilepsy, and neonatal diabetes mellitus; IPEX, immune dysregulation, polyendocrinopathy, enteropathy, and X-linked; TNDM, transient neonatal diabetes mellitus. The mean age of diagnosis among patients with WFS1 mutations is approximately 5 years 154. Presenting clinical features in patients with KATP-NDM suggest insulin dependency, with low or undetectable C-peptide levels and frequent presentation with diabetic ketoacidosis65 ].…”

Association of optic atrophy and type 1 diabetes: clinical hallmarks for the diagnosis of Wolfram syndrome

“…Full consent was obtained from the patient for the case publication WFS is a rare autosomal recessive disease characterized by DM1, optic atrophy, deafness, and diabetes insipidus 2,3 . The coexistence of DM1 and optic atrophy suggest WFS but molecular confirmation is mandatory 4 . Besides optic atrophy, MRI findings in WFS may include hyperintense signal in pons and in optic tracts, brainstem atrophy and absence of neurohypophyseal "bright signal" 5 .…”